RARE DISEASE
Buerger disease
Buerger disease
Buerger disease
Synonyms: Thromboangiitis obliterans
Synonyms: Thromboangiitis obliterans
Synonyms: Thromboangiitis obliterans
Drug discovery
12
drugs
With orphan designations
Overview
A non-atherosclerotic, inflammatory vascular disorder affecting small- and medium-sized arteries and veins, strongly associated with tobacco use. Presents with distal limb ischemia, claudication, rest pain, ulcers, or gangrene. Diagnosis requires exclusion of diabetes, autoimmune diseases, and hypercoagulable states. Smoking cessation is the only definitive therapy; untreated cases risk progressive tissue necrosis [1][5][9][14].
Therapies
Categories: rare circulatory system diseases, rare renal diseases, rare systemic and rheumatological diseases, rare transplant-related disorders
Research Papers
828 drug discovery papers about Buerger disease, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
828 drug discovery papers about Buerger disease, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-03 | [Exploration of effective substances and mechanisms of Corydalis Herba for treating thromboangiitis obliterans based on UHPLC-Q-TOF-MS/MS, network pharmacology, and molecular docking analyses].
Corydalis Herba is a traditional Tibetan medicine clinically applied to treat vasculitis and related conditions. Although many kinds of compounds have been isolated and identified from Corydalis Herba, there is no systematic mass spectrometry(MS) research on it, and its effective substances and mechanisms for treating thromboangiitis obliterans remain unknown. Therefore, one of the origins of Corydalis Herba, i.e., the dried herb of Corydalis hendersonii(CH), was used in this study, and ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS), network pharmacology, and molecular docking methods were used to investigate its chemical constituents as well as its effective substances and mechanisms for treating thromboangiitis obliterans. A total of 107 chemical constituents of CH were identified, and 17 of them were unequivocally identified by comparison with reference compounds. The 107 compounds comprise 74 alkaloids, 10 flavonoids, 14 organic acids, 7 amides, and 2 amines, and 89 of them were new constituents of Corydalis Herba, including 8 potential new compounds. In addition, the electrospray ionization(ESI) MS fragmentation patterns of different types of benzyltetrahydroisoquinoline alkaloids were proposed. Finally, 16 core targets(SERPINE1, ICAM1, MMP9, VCAM1, SELE, F3, MPO, etc.), 85 active ingredients, 26 effective substances, and 10 key effective substances(protopine, naringenin, berberine, tetrahydropalmatine, kaempferol, higenamine, apigenin, luteolin, quercetin, and tetrahydrocoptisine) of CH in the treatment of thromboangiitis obliterans were determined by network pharmacology, molecular docking analyses, and literature retrieval. The results lay a solid foundation for further research on the quality control, pharmacological effects, mechanisms, and in vivo process of Corydalis Herba.
2026-07-10 | Systemic Exposure and Multicomponent Pharmacokinetics of Mailuoning Oral Liquid: Integrated Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry Profiling and Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry Quantification.
Mailuoning oral liquid (MLN) is a state-approved multi-herb formula that has been prescribed for 25 years to clear heat, nourish yin, invigorate blood, and resolve stasis. Although randomized controlled trials and real-world evidence support its efficacy in thromboangiitis obliterans, deep-vein thrombosis, and the convalescent phase of cerebral infarction, a systematic search identified no pharmacokinetic data on its bioactive constituents. This lack of pharmacokinetic data impedes evidence-based dose refinement and international acceptance. Here, we employed ultra-high-performance liquid chromatography with Quadrupole-Exactive Orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap HRMS) to track 39 MLN-derived compounds in rat plasma, intestinal contents, and 10 tissues; 15 with prominent systemic exposure were designated as key pharmacokinetic markers. A selective and sensitive UHPLC-tandem MS assay was subsequently developed and fully validated for simultaneous quantification of these 15 circulating components. The assay exhibited excellent linearity (r ≥ 0.9974) for all analytes, with precision, accuracy, extraction recovery, and matrix effects meeting standard bioanalytical validation criteria. All compounds demonstrated stability under the tested storage conditions. Following oral administration of MLN at 8.1 and 16.2 mL·kg-1 in rats, all 15 components were rapidly absorbed, reaching peak plasma concentrations within approximately 1 h. Systemic exposure increased in a clear dose-dependent manner, with structurally related compounds showing similar pharmacokinetic profiles. Notably, the iridoids secoxyloganin, harpagide, and secologanic acid yielded the highest AUC0-24 h values, indicating they are the principal systemic exposure markers. This study establishes the first comprehensive pharmacokinetic profile for MLN and provides a robust, validated analytical platform. By creating a crucial link between quantitative systemic exposure and efficacy, our work supplies a scientific foundation for refining dosage regimens, establishing quality specifications, and promoting the evidence-based clinical application of this widely prescribed traditional Chinese medicine formula.
2026-07-01 | Preliminary clinical observation of a novel anticoagulation regimen in the acute phase of thromboangiitis obliterans (Buerger's disease)
Preliminary clinical observation of a novel anticoagulation regimen in the acute phase of thromboangiitis obliterans (Buerger's disease)
2026-06-26 | BUERGER’S DISEASE - A GENERAL OVERVIEW WITH A FOCUS ON NEW THERAPEUTIC APPROACHES
Introduction: Buerger's disease (thromboangiitis obliterans, TAO) is an inflammatory disease affecting small and medium-sized blood vessels, primarily in the extremities. This condition leads to their gradual narrowing and occlusion, resulting in impaired blood flow and tissue ischemia. It most often affects young adults, particularly men. It is strongly associated with tobacco use, which is considered a key risk factor for disease development and progression. Clinical presentation includes limb pain, intermittent claudication, ulceration, and, in advanced cases, tissue necrosis. Although treatment is primarily centered on smoking cessation and symptom relief, recent advances in therapeutic approaches show promising potential. Purpose: The aim of this review is to discuss Buerger's disease in the context of its pathogenesis, diagnosis, and clinical presentation, and to analyze current therapeutic options. Methodology: A narrative literature review was conducted in PubMed to identify studies on thromboangiitis obliterans. The search strategy included the keywords "Buerger’s disease" (accounting for variant - "Buerger disease"), "thromboangiitis obliterans" and "treatment". Additionally, reference lists of selected articles were screened to identify further relevant publications. Studies published between 2000 and 2025 and directly related to the topic were included. Conclusions: Advances in the understanding and management of Buerger’s disease have led to the development of new therapeutic approaches. However, current evidence remains limited, and further well-designed studies are needed to establish optimal treatment strategies and improve patient outcomes.
2026-05-22 | Buerger’s Disease- Ayurved Chikista -Case Study
Buerger’s disease is a segmental, progressive, occlusive, inflammatory disease of small and medium sized vessels with superficial thrombophlebitis often may present as Raynaud’s phenomenon with micro abscesses, along with neutrophil and giant cell infiltration, with skip lesions. Buerger's disease[Thromboangiitis Obliterans ] is a non-atherosclerotic inflammatory disease of unknown etiology, which has a strong association with tobacco. More common in lower limbs than upper limbs Incidence is Very commonly seen in young and middle aged males (20 – 40 yrs.) Seen only in smokers and tobacco users . Hormonal influence, familial factors Hypersensitivity to cigarette, Altered autonomic functions, Lower socioeconomic group, Recurrent minor feet injuries, Poor hygiene. Pathogenesis Smoke- carbon monoxide and nicotinic acid Vasospasm &hyperplasia of intima Thrombosis of vessels Obliteration of vessels Panarteritis – segmental Artery ,vein and nerve are together involved ,Nerve involvement due to blockage of vasa nervosa causes rest pain . Artery involvement leads to features like claudication pain. With blockage – plenty of collaterals open up Collaterals maintain the blood supply to the ischemic area this is known as compensatory peripheral vascular disease. Disease progression due to smoking leads to blockage of collaterals also leading to severe ischemia known as decompensatory peripheral vascular disease or critical limb ischemia. we present here one case successfully treated with the help of classical ayurveda management.
gene therapies
2025-04-13 | Seltoplasmid promotes ulcer healing versus placebo for treating patients with chronic limb-threatening ischemia: HOPE CLTI-2 trial.
Intramuscular injection of donaperminogene seltoplasmid (recombinant human hepatocyte growth factor plasmids) represents a gene therapy that treats patients with chronic limb-threatening ischemia (CLTI). The HOPE CLTI-2 trial was a phase 3, multicenter, double-blind, placebo-controlled study aimed to evaluate the efficacy and safety of seltoplasmid in patients with Rutherford class 5 CLTI. This study did not require participants to be ineligible for revascularization, allowing enrollment of patients with CLTI caused by either atherosclerosis (ASO) or Buerger disease (or thromboangiitis obliterans [TAO]). The primary endpoint was the complete ulcer healing rate at 6 months. A total of 242 participants (53.3% ASO versus 46.7% TAO) were enrolled, with 161 receiving seltoplasmid and 81 receiving placebo. Complete ulcer healing was achieved in 70 patients in the seltoplasmid group compared to 15 patients in the placebo group, resulting in an adjusted healing rate difference of 26.1% (95% confidence interval [CI]: 15.1%-37.0%; p < 0.001). The hazard ratio for healing was 2.31 (95% CI: 1.32-4.05; p = 0.004). The benefits of seltoplasmid on ulcer healing persisted in both TAO and ASO subgroups. Serious adverse events were rare. Our study demonstrated that seltoplasmid significantly improved ulcer healing rates in patients with Rutherford class 5 CLTI compared to placebo.
2024-07-27 | Gene Therapy of Thromboangiitis Obliterans with Growth Factor Plasmid (VEGF165) and Autologous Bone Marrow Cells.
We performed gene therapy for critical limb ischemia in thromboangiitis obliterans (TAO) by the intramuscular administration of plasmids of the vascular endothelial growth factor gene (VEGF 165) with or without bone marrow-derived stem cells. The 21 patients were randomly assigned to three groups: A-with dual therapy, cells and plasmid; B-plasmid only; and C-control group, where patients received intramuscular injections of saline. Serum VEGF levels, the ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and the rest pain measured by the visual analog scale (VAS) were determined sequentially before treatment, and then 1 and 3 months after treatment. In the treatment groups, serum VEGF levels increased by 4 weeks and returned to baseline values after 3 months. ABI after 12 weeks increased by an average of 0.18 in group A, and 0.09 in group B and group C. TcPO2 increased by an average of 17.3 mmHg in group A, 14.1 mmHg in group B, and 10.7 mmHg in group C. The largest pain decrease was observed in group A and averaged 5.43 less pain intensity. Gene therapy using the VEGF plasmid along with or without bone marrow-derived mononuclear cells administered intramuscularly into an ischemic limb in TAO is a safe and effective therapy.
2021-07-12 | Combined Analysis of Clinical Data on HGF Gene Therapy to Treat Critical Limb Ischemia in Japan.
The objective of this combined analysis of data from clinical trials in Japan, using naked plasmid DNA encoding hepatocyte growth factor (HGF), was to document the safety and efficacy of intramuscular HGF gene therapy in patients with critical limb ischemia (CLI). HGF gene transfer was performed in 22 patients with CLI in a single-center open trial at Osaka University; 39 patients in a randomized, placebo-controlled, multi-center phase III trial, 10 patients with Buerger's disease in a multi-center open trial; and 6 patients with CLI in a multi-center open trial using 2 or 3 intramuscular injections of naked HGF plasmid at 2 or 4 mg. Resting pain on a visual analogue scale (VAS) and wound healing as primary endpoints were evaluated at 12 weeks after the initial injection. Serious adverse events caused by gene transfer were detected in 7 out of 77 patients (9.09%). Only one patient experienced peripheral edema (1.30%), in contrast to those who had undergone treatment with VEGF. At 12 weeks after gene transfer, combined evaluation of VAS and ischemic ulcer size demonstrated a significant improvement in HGF gene therapy group as compared to the placebo group (P=0.020). The long-term analysis revealed a sustained decrease in the size of ischemic ulcer in HGF gene therapy group. In addition, VAS score over 50 mm at baseline (total 27 patients) demonstrated a tendency (P=0.059), but not significant enough, to improve VAS score in HGF gene therapy as compared to the placebo group. The findings indicated that intramuscular injection of naked HGF plasmid tended to improve the resting pain and significantly decreased the size of the ischemic ulcer in the patients with CLI who did not have any alternative therapy, such as endovascular treatment (EVT) or bypass graft surgery. An HGF gene therapy product, CollategeneTM, was recently launched with conditional and time-limited approval in Japan to treat ischemic ulcer in patients with CLI. Further clinical trials would provide new therapeutic options for patients with CLI.
2019-08-14 | [Comprehensive treatment of a patient with Buerger's disease using genetically engineered complexes VEGF-165].
Buerger's disease, also known as thromboangiitis obliterans, is a severe invalidating systemic vascular disease. To one of the modern methods, which is distinguished by its radically new principles of action, as well as holding much promise for further study and application in treatment of patients with lower limb chronic ischaemia induced by thromboangiitis obliterans belongs the use of genetically engineered complexes based on vascular endothelial growth factor VEGF-165 ('Neovasculgen'). 'Neovasculgen' is a genetically engineered complex being a circular DNA (native plasmid on the CELO vector and Ad5), carrying the human VEGF-165 gene, encoding VEGF synthesis. Injection of this drug to the ischaemised tissues of lower extremities ensures long-term synthesis of vascular endothelial growth factor 165 leading to the development of an additional collateral vascular network and consequently to increased perfusion of tissues with oxygen and decreased degree of ischaemia. Presented herein is a clinical case report of a successful therapeutic outcome achieved in a patient suffering for a long time from thromboangiitis obliterans (Buerger's disease) and treated with genetically engineered complexes based on vascular endothelial growth factor ('Neovasculgen') used as a component of comprehensive conservative therapy. Болезнь Бюргера, или облитерирующий тромбангиит, представляет собой тяжелое инвалидизирующее системное заболевание сосудов. Одним из современных и кардинально новых по принципам действия, а также перспективным для дальнейшего изучения и применения в лечении больных с хронической ишемией нижних конечностей, вызванной облитерирующим тромбангиитом, является использование генно-инженерных конструкций на основе факторов роста эндотелия сосудов VEGF-165 (препарат 'Неоваскулген'). Препарат 'Неоваскулген' – это генно-инженерная конструкция, которая представляет собой кольцевую ДНК (нативная плазмида на векторе CELO и Ad5), несущую человеческий ген VEGF-165, кодирующий синтез фактора роста эндотелия сосудов. Введение данного лекарственного средства в ишемизированные ткани нижних конечностей пациента обеспечивает длительный синтез сосудистого эндотелиального фактора роста 165, приводящего к развитию дополнительной коллатеральной сосудистой сети и, следовательно, к увеличению перфузии тканей кислородом и снижению степени ишемии. Представлен клинический случай успешного лечения больного, страдающего длительное время облитерирующим тромбангиитом (болезнью Бюргера), с применением генно-инженерных конструкций на основе сосудистого эндотелиального фактора роста (препарат 'Неоваскулген') в составе комплексной консервативной терапии.
2014-07-01 | Pluronic® L64-mediated stable HIF-1α expression in muscle for therapeutic angiogenesis in mouse hindlimb ischemia
Intramuscular injection of plasmid DNA (pDNA) to express a therapeutic protein is a promising method for the treatment of many diseases. However, the therapeutic applications are usually hindered by gene delivery efficiency and expression level. In this study, critical factors in a pDNA-based gene therapy system, such as gene delivery materials, a therapeutic gene, and its regulatory elements, were optimized to establish an integrated system for the treatment of mouse hindlimb ischemia. The results showed that Pluronic L64 (L64) was an efficient and safe material for gene delivery into mouse skeletal muscle. It also showed intrinsic ability to promote in vivo angiogenesis in a concentration-dependent manner, which might be through the activation of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-regulated angiogenic factors. The combination of 0.1% L64 with a hybrid gene promoter (pSC) increased the gene expression level, elongated the gene expression duration, and enhanced the number of transfected muscle fibers. In mice ischemic limbs, a gene medicine (pSC-HIF1α(tri)/L64) composed of L64 and pSC-based expression plasmid encoding hypoxia-inducible factor 1-alpha triple mutant (HIF-1α(tri)), improved the expression of stable HIF-1α, and in turn, the expression of multiple angiogenic factors. As a result, the ischemic limbs showed accelerated function recovery, reduced foot necrosis, faster blood reperfusion, and higher capillary density. These results indicated that the pSC-HIF1α(tri)/L64 combination presented a potential and convenient venue for the treatment of peripheral vascular diseases, especially critical limb ischemia.
cell therapies
2025-11-26 | Possibilities for revascularization and closure of wound defects in lower limbs with critical ischemia through free gracilis flap transfer: review of 3 cases.
This article presents three clinical cases of lower limb revascularization with closure of trophic defects using free gracilis flap transfer; two patients with Buerger's disease and one patient with type 2 diabetes mellitus. In these cases, we also describe and discuss direct or indirect evidence of indirect revascularization of ischemic tissues by means of the flap, as well as the advantages and limitations of the free gracilis muscle flap.
2024-10-09 | Mesenchymal stromal cell therapy (REGENACIP®), a promising treatment option in chronic limb threatening ischemia - a narrative review.
Chronic Limb Threatening Ischemia (CLTI) is a challenging clinical problem associated with high morbidity and mortality. Endovascular interventions have been the cornerstone of treatment whenever possible. It is estimated that CLTI represents < 10% of all Peripheral Artery Disease patients, yet 50% of the patients end up either with a major amputation of the lower limbs or die of cardiovascular causes within one year period, especially in those with unsuccessful revascularization or "no-option" CLTI. Cell-based therapeutics, especially bone marrow-derived mesenchymal stromal cells have emerged as a potential, promising, and novel alternate therapeutic modality in the management of CLTI, bolstered with positive results in numerous research, including randomized and nonrandomized trials. REGENACIP® is one such BM-MSC therapy approved by Central Drugs Standard Control Organization in India for the management of "no-option" Atherosclerotic Peripheral Arterial disease / Buerger's disease patients with established critical limb ischemia in Rutherford Grade III-5 or III-6, not eligible for or have failed traditional revascularization treatment, with rest pain and / or ulcers in the affected limb. The current review aims to deliberate upon the various aspects of CLTI and clinical benefits of REGENACIP® therein.
2023-05-15 | A comparative experimental study of the efficacy and safety of Quality and Quantity media-cultured mononuclear cell transplantation in ischemic hindlimb mouse model
Abstract Background: Up to 15-20% of revascularizations for chronic limb-threatening ischemia (CLTI) fail. Peripheral blood mononuclear cell (PBMNC) transplantation is an alternative treatment for CLTI patients, but a meta-analysis study found no significant clinical benefit of this treatment. Impaired function and/or an insufficient number of PBMNCs in CLTI patients might be the cause of unsatisfactory outcomes. Quality and Quantity media-cultured mononuclear cells (QQMNCs) were reported to enhance the number and function of PBMNCs. Accordingly, the aim of this study was to investigate the efficacy and safety of QQMNC transplantation in an ischemic hindlimb mouse model. Methods: PBMNCs from CLTI patients were cultured in Quality and Quantity (QQ) culture media or standard culture media. In vitro studies, including phenotypic analysis of progenitor cells (CD34+CD133+), M2 macrophages (CD206+), and inactivated T regulatory cells (CD4+CD25+CD127+); colony forming assay; and tube formation assay of QQMNCs and PBMNCs, were conducted. Intramuscular transplantation of QQMNCs or PBMNCs was performed in the ischemic hindlimb mouse model. The clinical appearance of ischemic limbs was observed, and blood flow in ischemic limbs was measured using a laser Doppler perfusion imager. Transplantation outcomes were compared between the QQMNC and PBMNC groups. Results: Twenty CLTI patients (mean age: 65.9±8.56 years) were included. Diabetes mellitus, hypertension, current smoker status, and chronic kidney disease was found in 12, 17, 11, and 6 patients, respectively. The mean percentages of CD34+ cells, CD133+ cells, CD34+CD133+ progenitor cells, CD206+ cells, colony-forming cells, and tube formation were significantly higher in the QQMNC group than in the PBMNC group. However, the mean percentage of CD4+CD25+CD127+ cells was significantly lower in QQMNCs than in PBMNCs. The colony-forming unit count and Dil-acetylated low-density lipoprotein uptake were both significantly greater in QQMNCs than in PBMNCs. The clinical appearance of post-QQMNC-injected limbs was less severe than the appearance of post-PBMNC-injected limbs. Limb perfusion was significantly better in the QQMNC group than in the PBMNC group. Conclusions: Proangiogenic and anti-inflammatory phenotypes of MNCs cultured in QQ culture media were successfully reproduced in vitro . Moreover, intramuscular QQMNC transplantation was found to be safe, and resulted in better reperfusion of ischemic mouse hindlimbs compared to PBMNCs.
2021-01-13 | Risk Factors, Mechanisms and Treatments of Thromboangiitis Obliterans: An Overview of Recent Research.
Thromboangiitis obliterans (TAO) is a nonatherosclerotic thromboticocclusive vasculitis that affects the vessels of the small and medium-sized extremities. No explicit etiology or pathogenesis of TAO has been proven, and more effective treatments are needed. The study aimed to summarize and present an overview of recent advances regarding the risk factors, mechanisms and treatments of TAO and to organize the related information in figures to provide a comparatively complete reference. We searched PubMed for English-language literature about TAO without article type limits, including articles about the risk factors, pathological mechanisms and treatments of TAO in the last 10 years with essential supplements (references over ranges and English abstracts of Russian literature). After screening content of works of literature, 99 references were evaluated. We found that risk factors of TAO include smoking, gene factors and periodontal diseases. The underlying mechanism of TAO involves oxidative stress, immunity, hemodynamic changes, inflammation and so on. Moreover, similarities in genetic factors and cigarette relevance existed between periodontal diseases and TAO, so further study of relationship was required. For TAO treatment, medicine, endovascular intervention and revascularization surgery, autologous cell therapy and novel therapies were also mentioned. Besides, a hypothesis that infection triggers autoimmunity in TAO could be speculated, in which TLR4 plays a key role. 1. A hypothesis is put forward that infections can trigger autoimmunity in TAO development, in which TLR4, as a key agent, can activate immune signaling pathways and induce autoimmune cytokines expression. 2. It is suggested to reconsider the association between periodontal diseases and TAO, as they share the same high-risk population. Controlling periodontal disease severity in TAO studies may provide new clues. 3. For TAO treatment, endovascular intervention and autologous cell therapy both showed promising long-term therapeutic effectiveness, in which autologous cell therapy is becoming more popular, although more clinical comparisons are needed.
2019-11-04 | Outcome From a Randomized Controlled Clinical Trial - Improvement of Peripheral Arterial Disease by Granulocyte Colony-Stimulating Factor-Mobilized Autologous Peripheral-Blood-Mononuclear Cell Transplantation (IMPACT).
The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified.Methods and Results:A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage II-IV and Rutherford category 1-5) caused by arteriosclerosis obliterans or Buerger's disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was II/III in 82 patients and IV in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage II/III subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious. In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.
antibodies
2026-03-01 | PO:01:015 Thromboangiitis obliterans in antiphospholipid syndrome and treatment
Objectives To present a clinical case of two patients with resistant thromboangiitis obliterans, as a manifestation of antiphospholipid syndrome (APS), successfully treated with rituximab.Methods Two patients (men, aged 44 and 40, one of whom had been a long-time smoker) with high triple aPL positivity, occlusive artery disease and ischemia of the distal lower extremities received anticoagulants, aspirin, hydroxychloroquine, statins and a prostaglandin E1 analog (alprostadil).A 44-year-old man had a history of heart attack that had been treated with thrombolysis.The
2026-03-01 | PO:01:014 Cutaneous features and antibody profiles in primary and secondary antiphospholipid syndrome
Objectives To present a clinical case of two patients with resistant thromboangiitis obliterans, as a manifestation of antiphospholipid syndrome (APS), successfully treated with rituximab.Methods Two patients (men, aged 44 and 40, one of whom had been a long-time smoker) with high triple aPL positivity, occlusive artery disease and ischemia of the distal lower extremities received anticoagulants, aspirin, hydroxychloroquine, statins and a prostaglandin E1 analog (alprostadil).A 44-year-old man had a history of heart attack that had been treated with thrombolysis.
2024-03-28 | A scope systematic review to clarify immune response to tobacco in Buerger
Abstract Background Progressive Thromboangiitis Obliterans (TAO) is a progressive and segmental inflammatory disorder known as Buerger's disease that affects the medium and small arteries of the upper limbs. The major risk factor for Buerger's disease is cigarettes and tobacco products, which can activate several inflammatory and pre-inflammatory parameters. Methods For this systematic review, based on the accepted criteria of Prisma, we searched from 2017 to 2022 in PubMed, Web of Science, science direct and followed the results of Google Scholar cytokines. We reviewed the literature on these smoking-related immune parameters in Buerger's disease as a potential treatment for this disease. Results In TOA patients, IL-17, RORγt, HMGB1 and RAGE mRNA expression are positively correlated with symptom severity. TLR family is associated with changes in the TOA population as a significant difference in TLR4 in the resting and acute phases. TLR9 may also be responsible for the secretion of IL-8 TNF involves in inflammation, muscle weakness, and pain in TOA. significant difference of IL-33 levels between TOA patients, healthy smokers and non-smokers of this cytokine. Conclusion Our results suggest that Buerger's disease can be considered an autoimmune disease caused by smoking. Buerger increase pro-inflammation markers in TOA and reduce angiogenetic factors. We recommend that pro-inflammatory cytokines should be considered in treatment and diagnosis programs and further research should focus on them.
2018-05-01 | Treatment of multiple refractory ankle ulcerations in thromboangiitis obliterans
Rationale: Thromboangiitis obliterans (TAOs, or Buerger's disease) present as a non-atherosclerotic segmental occlusive vasculitis within medium- and small-sized blood vessels. TAO frequently occurs in young adults and is associated with cigarette smoking. At present, there are no accurately defined treatments for TAO. Patient concerns: A 34-year-old Asian woman with a 20-year history of heavy cigarette smoking and recurrent, small, and self-limited lower limb ulcerations since adolescence, presented with persisting unhealed ulcerations on both ankles for 6 months. Her wound healing response was poor following the 2-month administration of colchicine, prednisolone, hydroxychloroquine, and mycophenolic acid. Diagnosis: The patient was diagnosed with TAO with hyperimmunoglobulin E and refractory ulcerations on her ankles. Interventions: The patient received monthly omalizumab (300 mg) and previous medications for 2 months and shifted to omalizumab and colchicine without mycophenolic acid and hydroxychloroquine because of onychomadesis, which was considered to be a possible adverse drug reaction. Outcomes: The wounds healed almost completely. The administration of omalizumab and colchicine will be continued until they the wounds are fully healed. Lessons: Mycophenolic acid has a limited function in TAO treatment, especially in cases of refractory skin ulcerations. Omalizumab can be a valuable treatment option for patients with TAO and hyperimmunoglobulin E.
other
2022-02-22 | miR-100 alleviates the inflammatory damage and apoptosis of H2O2-induced human umbilical vein endothelial cells via inactivation of Notch signaling by targeting MMP9.
Thromboangiitis obliterans is a nonatherosclerotic segmental inflammatory disease, and miR-100 plays an anti-inflammatory role in chronic inflammation. Therefore, we hypothesized that miR-100 might alleviate the inflammatory damage and apoptosis of H2O2-induced ECV304 cells and aimed to investigate the relationship between miR-100 and thromboangiitis obliterans and the related molecular mechanism. Cell counting kit-8 was used to detect cell viability, and the expression of inflammatory factors and oxidative stress was measured by ELISA. TUNEL assay was used to detect the apoptosis of human umbilical vein endothelial cells after induction by H2O2. Furthermore, the interaction between miR-100 and matrix metalloproteinase-9 was verified by dual-luciferase assay. Quantitative reverse transcription polymerase chain reaction and western blot were used to detect the expression of the adhesion factors, apoptosis-related proteins and Notch pathway-related protein. The results revealed that miR-100 was decreased in H2O2-induced human umbilical vein endothelial cells. Overexpression of miR-100 attenuated inflammatory response and cell apoptosis in H2O2-induced human umbilical vein endothelial cells. The overexpression of miR-100 inhibited matrix metalloproteinase-9 expression in H2O2-induced human umbilical vein endothelial cells. miR-100 inhibited H2O2-induced human umbilical vein endothelial cell inflammation, oxidative stress, and cell apoptosis via inactivation of Notch signaling by targeting matrix metalloproteinase. Our study demonstrated that miR-100 reduced the inflammatory damage and apoptosis of H2O2-induced human umbilical vein endothelial cells via inactivation of Notch signaling by targeting matrix metalloproteinase. These findings suggested that miR-100 might be a novel therapeutic target for the prevention of thromboangiitis obliterans.
2021-12-23 | Thromboangiitis obliterans plasma-derived exosomal miR-223-5p inhibits cell viability and promotes cell apoptosis of human vascular smooth muscle cells by targeting VCAM1.
Background: Exosomes-encapsulated microRNAs (miRNAs) have been established to be implicated in the pathogenesis of different diseases. Nevertheless, circulating exosomal miRNAs of thromboangiitis obliterans (TAO) remains poorly understood. This study aimed to explore the effects of exosomal miRNAs associated with TAO on human vascular smooth muscle cells (HVSMCs).Methods: The exosomes were isolated from the plasma of TAO patients and normal controls and then were sent for small RNA sequencing. Differentially expressed miRNAs (DE-miRNAs) were identified by bioinformatics analysis and were confirmed by RT-qPCR. After that, PKH67 staining was used to label exosomes and co-cultured with HVSMCs. Cell viability and apoptosis were, respectively, tested by CCK-8 assay and flow cytometry. Finally, dual-luciferase reporter assay was used to confirm the downstream targets of miR-223-5p.Results: A total of 39 DE-miRNAs were identified between TAO patients and normal controls, of which, miR-223-5p was one of the most significantly up-regulated miRNAs. TAO plasma-derived exosomes or miR-223-5p mimics inhibited cell viability of HVSMCs and promoted cell apoptosis. The pro-apoptotic effect of TAO plasma-derived exosomes was alleviated by miR-223-5p inhibitor. Additionally, the expressions of VCAM1 and IGF1R were down-regulated by exosomes and miR-223-5p mimics, and were abrogated by miR-223-5p inhibitor. Dual-luciferase report showed that VCAM1 was the target of miR-223-5p.Conclusions: Our findings imply that circulating exosomal miR-223-5p may play an essential role in the pathogenesis of TAO, and provide a basis for miR-6515-5p/VCAM1 as novel therapeutic targets and pathways for TAO treatment.
2021-06-24 | MiR-223 alleviates thrombus and inflammation in thromboangiitis obliterans rats by regulating NLRP3.
The aim of this study was to observe the regulatory effects of micro ribonucleic acid (miR)-223 on thromboangiitis obliterans (TAO) rats, and to explore the potential regulatory mechanism. Online database TargetScan was used to predict the downstream regulatory targets of miR-223. A total of 45 Sprague Dawley (SD) rats were randomly divided into three groups, including sham operation group (Sham group), Model group, and miR-223 agonist group (miR-223 mimic group). TAO model was successfully established in rats through the injection of lauric acid via the femoral artery. The content of serum thromboxane B2 (TXB2) and endothelin (ET) was measured via enzyme-linked immunosorbent assay (ELISA). The pathological changes in the left hind limb were detected via hematoxylin-eosin (HE) staining. Moreover, the expressions of interleukin-6 (IL-6) and IL-1β in the tissues of the rat left hind limb were determined via immunohistochemistry. In addition, the protein expression of Nod-like receptor protein 3 (NLRP3) in tissues was determined using Western blotting. TargetScan database predicted that NLRP3 was the downstream target gene of miR-223. Compared with the Sham group, Model group exerted significantly higher content of serum TXB2 and ET, severe lesions in the rat left hind limb, as well as significantly increased expressions of IL-6 and IL-1β and protein expression of NLRP3 in tissues of the rat left hind limb (p<0.05). Besides, compared with the Model group, miR-223 mimic group showed remarkably lower content of serum TXB2 and ET, improved lesions in the rat left hind limb, as well as decreased expressions of IL-6 and IL-1β and protein expression of NLRP3 in the tissues of the rat left hind limb (p<0.05). MiR-223 agonist can alleviate thrombus and inflammatory response in TAO rats. The possible underlying mechanism may be related to targeted regulation on NLRP3 inflammasome expression.
2020-03-27 | Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial
Despite the important role that the growth hormone (GH)/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium is considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effects, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy is described. All the elements that trigger the local and systemic production of GH/IGF-I, as well as their possible roles both in physiological and pathological conditions are analyzed. All of the evidence is combined with important data from the GHAS trial, in which GH or a placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of ischemic disease.
2019-05-28 | Alleviation of A disintegrin and metalloprotease 10 (ADAM10) on thromboangiitis obliterans involves the HMGB1/RAGE/ NF-κB pathway.
Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a nonatherosclerotic inflammatory disease that influences medium- and small-sized blood vessels of extremities. However, mechanisms underlying TAO are still unclear. As a mediator associated with inflammation, A disintegrin and metalloprotease 10 (ADAM10) was hypothesized to play inhibitory roles in the development of TAO. Thus, the objective of this study is to investigate the effects of ADAM10 in a sodium laurate-induced TAO rat model and elucidate underlying mechanisms. Male Wistar rats were randomly divided into four groups (n = 6) for treatment: sham-operated (SHAM), TAO model (TAO), ADAM10 low dose injection (3 mg/kg; ADAM10-LD) and ADAM10 high dose injection (6 mg/kg; ADAM10-HD). After 14-day treatment, color Doppler ultrasound and hematology analysis indicated TAO rats displayed higher whole blood viscosity and blood platelet count compared with those in the SHAM group. Histologic evaluation and transmission electron microscopy revealed that the ultrastructural damages of vascular smooth muscle and endothelial cells were observed in TAO rats, such as fractured endoplasmic reticulum, decreased cell counts, and fibrillation. On the other hand, the typical signs and symptoms of TAO rats were significantly alleviated via ADAM10 treatment with a dose-dependent pattern. Real-time PCR and western blot results revealed that the expression of high-mobility-group box 1 (HMGB1), receptor for advanced glycation end-products (RAGE) and nuclear factor-kappa B (NF-κB) increased in TAO rats whereas decreased by ADAM10 treatment in both mRNA and protein levels. In conclusion, the results suggest ADAM10 alleviates symptoms of sodium laurate-induced TAO in rats via the RAGE/NF-κB signaling pathway and provides insight into the molecular basis and a potential therapeutic strategy for TAO.
small molecules
2026-08-03 | [Exploration of effective substances and mechanisms of Corydalis Herba for treating thromboangiitis obliterans based on UHPLC-Q-TOF-MS/MS, network pharmacology, and molecular docking analyses].
Corydalis Herba is a traditional Tibetan medicine clinically applied to treat vasculitis and related conditions. Although many kinds of compounds have been isolated and identified from Corydalis Herba, there is no systematic mass spectrometry(MS) research on it, and its effective substances and mechanisms for treating thromboangiitis obliterans remain unknown. Therefore, one of the origins of Corydalis Herba, i.e., the dried herb of Corydalis hendersonii(CH), was used in this study, and ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS), network pharmacology, and molecular docking methods were used to investigate its chemical constituents as well as its effective substances and mechanisms for treating thromboangiitis obliterans. A total of 107 chemical constituents of CH were identified, and 17 of them were unequivocally identified by comparison with reference compounds. The 107 compounds comprise 74 alkaloids, 10 flavonoids, 14 organic acids, 7 amides, and 2 amines, and 89 of them were new constituents of Corydalis Herba, including 8 potential new compounds. In addition, the electrospray ionization(ESI) MS fragmentation patterns of different types of benzyltetrahydroisoquinoline alkaloids were proposed. Finally, 16 core targets(SERPINE1, ICAM1, MMP9, VCAM1, SELE, F3, MPO, etc.), 85 active ingredients, 26 effective substances, and 10 key effective substances(protopine, naringenin, berberine, tetrahydropalmatine, kaempferol, higenamine, apigenin, luteolin, quercetin, and tetrahydrocoptisine) of CH in the treatment of thromboangiitis obliterans were determined by network pharmacology, molecular docking analyses, and literature retrieval. The results lay a solid foundation for further research on the quality control, pharmacological effects, mechanisms, and in vivo process of Corydalis Herba.
2026-07-10 | Systemic Exposure and Multicomponent Pharmacokinetics of Mailuoning Oral Liquid: Integrated Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry Profiling and Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry Quantification.
Mailuoning oral liquid (MLN) is a state-approved multi-herb formula that has been prescribed for 25 years to clear heat, nourish yin, invigorate blood, and resolve stasis. Although randomized controlled trials and real-world evidence support its efficacy in thromboangiitis obliterans, deep-vein thrombosis, and the convalescent phase of cerebral infarction, a systematic search identified no pharmacokinetic data on its bioactive constituents. This lack of pharmacokinetic data impedes evidence-based dose refinement and international acceptance. Here, we employed ultra-high-performance liquid chromatography with Quadrupole-Exactive Orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap HRMS) to track 39 MLN-derived compounds in rat plasma, intestinal contents, and 10 tissues; 15 with prominent systemic exposure were designated as key pharmacokinetic markers. A selective and sensitive UHPLC-tandem MS assay was subsequently developed and fully validated for simultaneous quantification of these 15 circulating components. The assay exhibited excellent linearity (r ≥ 0.9974) for all analytes, with precision, accuracy, extraction recovery, and matrix effects meeting standard bioanalytical validation criteria. All compounds demonstrated stability under the tested storage conditions. Following oral administration of MLN at 8.1 and 16.2 mL·kg-1 in rats, all 15 components were rapidly absorbed, reaching peak plasma concentrations within approximately 1 h. Systemic exposure increased in a clear dose-dependent manner, with structurally related compounds showing similar pharmacokinetic profiles. Notably, the iridoids secoxyloganin, harpagide, and secologanic acid yielded the highest AUC0-24 h values, indicating they are the principal systemic exposure markers. This study establishes the first comprehensive pharmacokinetic profile for MLN and provides a robust, validated analytical platform. By creating a crucial link between quantitative systemic exposure and efficacy, our work supplies a scientific foundation for refining dosage regimens, establishing quality specifications, and promoting the evidence-based clinical application of this widely prescribed traditional Chinese medicine formula.
2026-07-01 | Preliminary clinical observation of a novel anticoagulation regimen in the acute phase of thromboangiitis obliterans (Buerger's disease)
Preliminary clinical observation of a novel anticoagulation regimen in the acute phase of thromboangiitis obliterans (Buerger's disease)
2026-06-26 | BUERGER’S DISEASE - A GENERAL OVERVIEW WITH A FOCUS ON NEW THERAPEUTIC APPROACHES
Introduction: Buerger's disease (thromboangiitis obliterans, TAO) is an inflammatory disease affecting small and medium-sized blood vessels, primarily in the extremities. This condition leads to their gradual narrowing and occlusion, resulting in impaired blood flow and tissue ischemia. It most often affects young adults, particularly men. It is strongly associated with tobacco use, which is considered a key risk factor for disease development and progression. Clinical presentation includes limb pain, intermittent claudication, ulceration, and, in advanced cases, tissue necrosis. Although treatment is primarily centered on smoking cessation and symptom relief, recent advances in therapeutic approaches show promising potential. Purpose: The aim of this review is to discuss Buerger's disease in the context of its pathogenesis, diagnosis, and clinical presentation, and to analyze current therapeutic options. Methodology: A narrative literature review was conducted in PubMed to identify studies on thromboangiitis obliterans. The search strategy included the keywords "Buerger’s disease" (accounting for variant - "Buerger disease"), "thromboangiitis obliterans" and "treatment". Additionally, reference lists of selected articles were screened to identify further relevant publications. Studies published between 2000 and 2025 and directly related to the topic were included. Conclusions: Advances in the understanding and management of Buerger’s disease have led to the development of new therapeutic approaches. However, current evidence remains limited, and further well-designed studies are needed to establish optimal treatment strategies and improve patient outcomes.
2026-05-22 | Buerger’s Disease- Ayurved Chikista -Case Study
Buerger’s disease is a segmental, progressive, occlusive, inflammatory disease of small and medium sized vessels with superficial thrombophlebitis often may present as Raynaud’s phenomenon with micro abscesses, along with neutrophil and giant cell infiltration, with skip lesions. Buerger's disease[Thromboangiitis Obliterans ] is a non-atherosclerotic inflammatory disease of unknown etiology, which has a strong association with tobacco. More common in lower limbs than upper limbs Incidence is Very commonly seen in young and middle aged males (20 – 40 yrs.) Seen only in smokers and tobacco users . Hormonal influence, familial factors Hypersensitivity to cigarette, Altered autonomic functions, Lower socioeconomic group, Recurrent minor feet injuries, Poor hygiene. Pathogenesis Smoke- carbon monoxide and nicotinic acid Vasospasm &hyperplasia of intima Thrombosis of vessels Obliteration of vessels Panarteritis – segmental Artery ,vein and nerve are together involved ,Nerve involvement due to blockage of vasa nervosa causes rest pain . Artery involvement leads to features like claudication pain. With blockage – plenty of collaterals open up Collaterals maintain the blood supply to the ischemic area this is known as compensatory peripheral vascular disease. Disease progression due to smoking leads to blockage of collaterals also leading to severe ischemia known as decompensatory peripheral vascular disease or critical limb ischemia. we present here one case successfully treated with the help of classical ayurveda management.
gene therapies
2025-04-13 | Seltoplasmid promotes ulcer healing versus placebo for treating patients with chronic limb-threatening ischemia: HOPE CLTI-2 trial.
Intramuscular injection of donaperminogene seltoplasmid (recombinant human hepatocyte growth factor plasmids) represents a gene therapy that treats patients with chronic limb-threatening ischemia (CLTI). The HOPE CLTI-2 trial was a phase 3, multicenter, double-blind, placebo-controlled study aimed to evaluate the efficacy and safety of seltoplasmid in patients with Rutherford class 5 CLTI. This study did not require participants to be ineligible for revascularization, allowing enrollment of patients with CLTI caused by either atherosclerosis (ASO) or Buerger disease (or thromboangiitis obliterans [TAO]). The primary endpoint was the complete ulcer healing rate at 6 months. A total of 242 participants (53.3% ASO versus 46.7% TAO) were enrolled, with 161 receiving seltoplasmid and 81 receiving placebo. Complete ulcer healing was achieved in 70 patients in the seltoplasmid group compared to 15 patients in the placebo group, resulting in an adjusted healing rate difference of 26.1% (95% confidence interval [CI]: 15.1%-37.0%; p < 0.001). The hazard ratio for healing was 2.31 (95% CI: 1.32-4.05; p = 0.004). The benefits of seltoplasmid on ulcer healing persisted in both TAO and ASO subgroups. Serious adverse events were rare. Our study demonstrated that seltoplasmid significantly improved ulcer healing rates in patients with Rutherford class 5 CLTI compared to placebo.
2024-07-27 | Gene Therapy of Thromboangiitis Obliterans with Growth Factor Plasmid (VEGF165) and Autologous Bone Marrow Cells.
We performed gene therapy for critical limb ischemia in thromboangiitis obliterans (TAO) by the intramuscular administration of plasmids of the vascular endothelial growth factor gene (VEGF 165) with or without bone marrow-derived stem cells. The 21 patients were randomly assigned to three groups: A-with dual therapy, cells and plasmid; B-plasmid only; and C-control group, where patients received intramuscular injections of saline. Serum VEGF levels, the ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and the rest pain measured by the visual analog scale (VAS) were determined sequentially before treatment, and then 1 and 3 months after treatment. In the treatment groups, serum VEGF levels increased by 4 weeks and returned to baseline values after 3 months. ABI after 12 weeks increased by an average of 0.18 in group A, and 0.09 in group B and group C. TcPO2 increased by an average of 17.3 mmHg in group A, 14.1 mmHg in group B, and 10.7 mmHg in group C. The largest pain decrease was observed in group A and averaged 5.43 less pain intensity. Gene therapy using the VEGF plasmid along with or without bone marrow-derived mononuclear cells administered intramuscularly into an ischemic limb in TAO is a safe and effective therapy.
2021-07-12 | Combined Analysis of Clinical Data on HGF Gene Therapy to Treat Critical Limb Ischemia in Japan.
The objective of this combined analysis of data from clinical trials in Japan, using naked plasmid DNA encoding hepatocyte growth factor (HGF), was to document the safety and efficacy of intramuscular HGF gene therapy in patients with critical limb ischemia (CLI). HGF gene transfer was performed in 22 patients with CLI in a single-center open trial at Osaka University; 39 patients in a randomized, placebo-controlled, multi-center phase III trial, 10 patients with Buerger's disease in a multi-center open trial; and 6 patients with CLI in a multi-center open trial using 2 or 3 intramuscular injections of naked HGF plasmid at 2 or 4 mg. Resting pain on a visual analogue scale (VAS) and wound healing as primary endpoints were evaluated at 12 weeks after the initial injection. Serious adverse events caused by gene transfer were detected in 7 out of 77 patients (9.09%). Only one patient experienced peripheral edema (1.30%), in contrast to those who had undergone treatment with VEGF. At 12 weeks after gene transfer, combined evaluation of VAS and ischemic ulcer size demonstrated a significant improvement in HGF gene therapy group as compared to the placebo group (P=0.020). The long-term analysis revealed a sustained decrease in the size of ischemic ulcer in HGF gene therapy group. In addition, VAS score over 50 mm at baseline (total 27 patients) demonstrated a tendency (P=0.059), but not significant enough, to improve VAS score in HGF gene therapy as compared to the placebo group. The findings indicated that intramuscular injection of naked HGF plasmid tended to improve the resting pain and significantly decreased the size of the ischemic ulcer in the patients with CLI who did not have any alternative therapy, such as endovascular treatment (EVT) or bypass graft surgery. An HGF gene therapy product, CollategeneTM, was recently launched with conditional and time-limited approval in Japan to treat ischemic ulcer in patients with CLI. Further clinical trials would provide new therapeutic options for patients with CLI.
2019-08-14 | [Comprehensive treatment of a patient with Buerger's disease using genetically engineered complexes VEGF-165].
Buerger's disease, also known as thromboangiitis obliterans, is a severe invalidating systemic vascular disease. To one of the modern methods, which is distinguished by its radically new principles of action, as well as holding much promise for further study and application in treatment of patients with lower limb chronic ischaemia induced by thromboangiitis obliterans belongs the use of genetically engineered complexes based on vascular endothelial growth factor VEGF-165 ('Neovasculgen'). 'Neovasculgen' is a genetically engineered complex being a circular DNA (native plasmid on the CELO vector and Ad5), carrying the human VEGF-165 gene, encoding VEGF synthesis. Injection of this drug to the ischaemised tissues of lower extremities ensures long-term synthesis of vascular endothelial growth factor 165 leading to the development of an additional collateral vascular network and consequently to increased perfusion of tissues with oxygen and decreased degree of ischaemia. Presented herein is a clinical case report of a successful therapeutic outcome achieved in a patient suffering for a long time from thromboangiitis obliterans (Buerger's disease) and treated with genetically engineered complexes based on vascular endothelial growth factor ('Neovasculgen') used as a component of comprehensive conservative therapy. Болезнь Бюргера, или облитерирующий тромбангиит, представляет собой тяжелое инвалидизирующее системное заболевание сосудов. Одним из современных и кардинально новых по принципам действия, а также перспективным для дальнейшего изучения и применения в лечении больных с хронической ишемией нижних конечностей, вызванной облитерирующим тромбангиитом, является использование генно-инженерных конструкций на основе факторов роста эндотелия сосудов VEGF-165 (препарат 'Неоваскулген'). Препарат 'Неоваскулген' – это генно-инженерная конструкция, которая представляет собой кольцевую ДНК (нативная плазмида на векторе CELO и Ad5), несущую человеческий ген VEGF-165, кодирующий синтез фактора роста эндотелия сосудов. Введение данного лекарственного средства в ишемизированные ткани нижних конечностей пациента обеспечивает длительный синтез сосудистого эндотелиального фактора роста 165, приводящего к развитию дополнительной коллатеральной сосудистой сети и, следовательно, к увеличению перфузии тканей кислородом и снижению степени ишемии. Представлен клинический случай успешного лечения больного, страдающего длительное время облитерирующим тромбангиитом (болезнью Бюргера), с применением генно-инженерных конструкций на основе сосудистого эндотелиального фактора роста (препарат 'Неоваскулген') в составе комплексной консервативной терапии.
2014-07-01 | Pluronic® L64-mediated stable HIF-1α expression in muscle for therapeutic angiogenesis in mouse hindlimb ischemia
Intramuscular injection of plasmid DNA (pDNA) to express a therapeutic protein is a promising method for the treatment of many diseases. However, the therapeutic applications are usually hindered by gene delivery efficiency and expression level. In this study, critical factors in a pDNA-based gene therapy system, such as gene delivery materials, a therapeutic gene, and its regulatory elements, were optimized to establish an integrated system for the treatment of mouse hindlimb ischemia. The results showed that Pluronic L64 (L64) was an efficient and safe material for gene delivery into mouse skeletal muscle. It also showed intrinsic ability to promote in vivo angiogenesis in a concentration-dependent manner, which might be through the activation of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-regulated angiogenic factors. The combination of 0.1% L64 with a hybrid gene promoter (pSC) increased the gene expression level, elongated the gene expression duration, and enhanced the number of transfected muscle fibers. In mice ischemic limbs, a gene medicine (pSC-HIF1α(tri)/L64) composed of L64 and pSC-based expression plasmid encoding hypoxia-inducible factor 1-alpha triple mutant (HIF-1α(tri)), improved the expression of stable HIF-1α, and in turn, the expression of multiple angiogenic factors. As a result, the ischemic limbs showed accelerated function recovery, reduced foot necrosis, faster blood reperfusion, and higher capillary density. These results indicated that the pSC-HIF1α(tri)/L64 combination presented a potential and convenient venue for the treatment of peripheral vascular diseases, especially critical limb ischemia.
cell therapies
2025-11-26 | Possibilities for revascularization and closure of wound defects in lower limbs with critical ischemia through free gracilis flap transfer: review of 3 cases.
This article presents three clinical cases of lower limb revascularization with closure of trophic defects using free gracilis flap transfer; two patients with Buerger's disease and one patient with type 2 diabetes mellitus. In these cases, we also describe and discuss direct or indirect evidence of indirect revascularization of ischemic tissues by means of the flap, as well as the advantages and limitations of the free gracilis muscle flap.
2024-10-09 | Mesenchymal stromal cell therapy (REGENACIP®), a promising treatment option in chronic limb threatening ischemia - a narrative review.
Chronic Limb Threatening Ischemia (CLTI) is a challenging clinical problem associated with high morbidity and mortality. Endovascular interventions have been the cornerstone of treatment whenever possible. It is estimated that CLTI represents < 10% of all Peripheral Artery Disease patients, yet 50% of the patients end up either with a major amputation of the lower limbs or die of cardiovascular causes within one year period, especially in those with unsuccessful revascularization or "no-option" CLTI. Cell-based therapeutics, especially bone marrow-derived mesenchymal stromal cells have emerged as a potential, promising, and novel alternate therapeutic modality in the management of CLTI, bolstered with positive results in numerous research, including randomized and nonrandomized trials. REGENACIP® is one such BM-MSC therapy approved by Central Drugs Standard Control Organization in India for the management of "no-option" Atherosclerotic Peripheral Arterial disease / Buerger's disease patients with established critical limb ischemia in Rutherford Grade III-5 or III-6, not eligible for or have failed traditional revascularization treatment, with rest pain and / or ulcers in the affected limb. The current review aims to deliberate upon the various aspects of CLTI and clinical benefits of REGENACIP® therein.
2023-05-15 | A comparative experimental study of the efficacy and safety of Quality and Quantity media-cultured mononuclear cell transplantation in ischemic hindlimb mouse model
Abstract Background: Up to 15-20% of revascularizations for chronic limb-threatening ischemia (CLTI) fail. Peripheral blood mononuclear cell (PBMNC) transplantation is an alternative treatment for CLTI patients, but a meta-analysis study found no significant clinical benefit of this treatment. Impaired function and/or an insufficient number of PBMNCs in CLTI patients might be the cause of unsatisfactory outcomes. Quality and Quantity media-cultured mononuclear cells (QQMNCs) were reported to enhance the number and function of PBMNCs. Accordingly, the aim of this study was to investigate the efficacy and safety of QQMNC transplantation in an ischemic hindlimb mouse model. Methods: PBMNCs from CLTI patients were cultured in Quality and Quantity (QQ) culture media or standard culture media. In vitro studies, including phenotypic analysis of progenitor cells (CD34+CD133+), M2 macrophages (CD206+), and inactivated T regulatory cells (CD4+CD25+CD127+); colony forming assay; and tube formation assay of QQMNCs and PBMNCs, were conducted. Intramuscular transplantation of QQMNCs or PBMNCs was performed in the ischemic hindlimb mouse model. The clinical appearance of ischemic limbs was observed, and blood flow in ischemic limbs was measured using a laser Doppler perfusion imager. Transplantation outcomes were compared between the QQMNC and PBMNC groups. Results: Twenty CLTI patients (mean age: 65.9±8.56 years) were included. Diabetes mellitus, hypertension, current smoker status, and chronic kidney disease was found in 12, 17, 11, and 6 patients, respectively. The mean percentages of CD34+ cells, CD133+ cells, CD34+CD133+ progenitor cells, CD206+ cells, colony-forming cells, and tube formation were significantly higher in the QQMNC group than in the PBMNC group. However, the mean percentage of CD4+CD25+CD127+ cells was significantly lower in QQMNCs than in PBMNCs. The colony-forming unit count and Dil-acetylated low-density lipoprotein uptake were both significantly greater in QQMNCs than in PBMNCs. The clinical appearance of post-QQMNC-injected limbs was less severe than the appearance of post-PBMNC-injected limbs. Limb perfusion was significantly better in the QQMNC group than in the PBMNC group. Conclusions: Proangiogenic and anti-inflammatory phenotypes of MNCs cultured in QQ culture media were successfully reproduced in vitro . Moreover, intramuscular QQMNC transplantation was found to be safe, and resulted in better reperfusion of ischemic mouse hindlimbs compared to PBMNCs.
2021-01-13 | Risk Factors, Mechanisms and Treatments of Thromboangiitis Obliterans: An Overview of Recent Research.
Thromboangiitis obliterans (TAO) is a nonatherosclerotic thromboticocclusive vasculitis that affects the vessels of the small and medium-sized extremities. No explicit etiology or pathogenesis of TAO has been proven, and more effective treatments are needed. The study aimed to summarize and present an overview of recent advances regarding the risk factors, mechanisms and treatments of TAO and to organize the related information in figures to provide a comparatively complete reference. We searched PubMed for English-language literature about TAO without article type limits, including articles about the risk factors, pathological mechanisms and treatments of TAO in the last 10 years with essential supplements (references over ranges and English abstracts of Russian literature). After screening content of works of literature, 99 references were evaluated. We found that risk factors of TAO include smoking, gene factors and periodontal diseases. The underlying mechanism of TAO involves oxidative stress, immunity, hemodynamic changes, inflammation and so on. Moreover, similarities in genetic factors and cigarette relevance existed between periodontal diseases and TAO, so further study of relationship was required. For TAO treatment, medicine, endovascular intervention and revascularization surgery, autologous cell therapy and novel therapies were also mentioned. Besides, a hypothesis that infection triggers autoimmunity in TAO could be speculated, in which TLR4 plays a key role. 1. A hypothesis is put forward that infections can trigger autoimmunity in TAO development, in which TLR4, as a key agent, can activate immune signaling pathways and induce autoimmune cytokines expression. 2. It is suggested to reconsider the association between periodontal diseases and TAO, as they share the same high-risk population. Controlling periodontal disease severity in TAO studies may provide new clues. 3. For TAO treatment, endovascular intervention and autologous cell therapy both showed promising long-term therapeutic effectiveness, in which autologous cell therapy is becoming more popular, although more clinical comparisons are needed.
2019-11-04 | Outcome From a Randomized Controlled Clinical Trial - Improvement of Peripheral Arterial Disease by Granulocyte Colony-Stimulating Factor-Mobilized Autologous Peripheral-Blood-Mononuclear Cell Transplantation (IMPACT).
The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified.Methods and Results:A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage II-IV and Rutherford category 1-5) caused by arteriosclerosis obliterans or Buerger's disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was II/III in 82 patients and IV in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage II/III subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious. In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.
antibodies
2026-03-01 | PO:01:015 Thromboangiitis obliterans in antiphospholipid syndrome and treatment
Objectives To present a clinical case of two patients with resistant thromboangiitis obliterans, as a manifestation of antiphospholipid syndrome (APS), successfully treated with rituximab.Methods Two patients (men, aged 44 and 40, one of whom had been a long-time smoker) with high triple aPL positivity, occlusive artery disease and ischemia of the distal lower extremities received anticoagulants, aspirin, hydroxychloroquine, statins and a prostaglandin E1 analog (alprostadil).A 44-year-old man had a history of heart attack that had been treated with thrombolysis.The
2026-03-01 | PO:01:014 Cutaneous features and antibody profiles in primary and secondary antiphospholipid syndrome
Objectives To present a clinical case of two patients with resistant thromboangiitis obliterans, as a manifestation of antiphospholipid syndrome (APS), successfully treated with rituximab.Methods Two patients (men, aged 44 and 40, one of whom had been a long-time smoker) with high triple aPL positivity, occlusive artery disease and ischemia of the distal lower extremities received anticoagulants, aspirin, hydroxychloroquine, statins and a prostaglandin E1 analog (alprostadil).A 44-year-old man had a history of heart attack that had been treated with thrombolysis.
2024-03-28 | A scope systematic review to clarify immune response to tobacco in Buerger
Abstract Background Progressive Thromboangiitis Obliterans (TAO) is a progressive and segmental inflammatory disorder known as Buerger's disease that affects the medium and small arteries of the upper limbs. The major risk factor for Buerger's disease is cigarettes and tobacco products, which can activate several inflammatory and pre-inflammatory parameters. Methods For this systematic review, based on the accepted criteria of Prisma, we searched from 2017 to 2022 in PubMed, Web of Science, science direct and followed the results of Google Scholar cytokines. We reviewed the literature on these smoking-related immune parameters in Buerger's disease as a potential treatment for this disease. Results In TOA patients, IL-17, RORγt, HMGB1 and RAGE mRNA expression are positively correlated with symptom severity. TLR family is associated with changes in the TOA population as a significant difference in TLR4 in the resting and acute phases. TLR9 may also be responsible for the secretion of IL-8 TNF involves in inflammation, muscle weakness, and pain in TOA. significant difference of IL-33 levels between TOA patients, healthy smokers and non-smokers of this cytokine. Conclusion Our results suggest that Buerger's disease can be considered an autoimmune disease caused by smoking. Buerger increase pro-inflammation markers in TOA and reduce angiogenetic factors. We recommend that pro-inflammatory cytokines should be considered in treatment and diagnosis programs and further research should focus on them.
2018-05-01 | Treatment of multiple refractory ankle ulcerations in thromboangiitis obliterans
Rationale: Thromboangiitis obliterans (TAOs, or Buerger's disease) present as a non-atherosclerotic segmental occlusive vasculitis within medium- and small-sized blood vessels. TAO frequently occurs in young adults and is associated with cigarette smoking. At present, there are no accurately defined treatments for TAO. Patient concerns: A 34-year-old Asian woman with a 20-year history of heavy cigarette smoking and recurrent, small, and self-limited lower limb ulcerations since adolescence, presented with persisting unhealed ulcerations on both ankles for 6 months. Her wound healing response was poor following the 2-month administration of colchicine, prednisolone, hydroxychloroquine, and mycophenolic acid. Diagnosis: The patient was diagnosed with TAO with hyperimmunoglobulin E and refractory ulcerations on her ankles. Interventions: The patient received monthly omalizumab (300 mg) and previous medications for 2 months and shifted to omalizumab and colchicine without mycophenolic acid and hydroxychloroquine because of onychomadesis, which was considered to be a possible adverse drug reaction. Outcomes: The wounds healed almost completely. The administration of omalizumab and colchicine will be continued until they the wounds are fully healed. Lessons: Mycophenolic acid has a limited function in TAO treatment, especially in cases of refractory skin ulcerations. Omalizumab can be a valuable treatment option for patients with TAO and hyperimmunoglobulin E.
other
2022-02-22 | miR-100 alleviates the inflammatory damage and apoptosis of H2O2-induced human umbilical vein endothelial cells via inactivation of Notch signaling by targeting MMP9.
Thromboangiitis obliterans is a nonatherosclerotic segmental inflammatory disease, and miR-100 plays an anti-inflammatory role in chronic inflammation. Therefore, we hypothesized that miR-100 might alleviate the inflammatory damage and apoptosis of H2O2-induced ECV304 cells and aimed to investigate the relationship between miR-100 and thromboangiitis obliterans and the related molecular mechanism. Cell counting kit-8 was used to detect cell viability, and the expression of inflammatory factors and oxidative stress was measured by ELISA. TUNEL assay was used to detect the apoptosis of human umbilical vein endothelial cells after induction by H2O2. Furthermore, the interaction between miR-100 and matrix metalloproteinase-9 was verified by dual-luciferase assay. Quantitative reverse transcription polymerase chain reaction and western blot were used to detect the expression of the adhesion factors, apoptosis-related proteins and Notch pathway-related protein. The results revealed that miR-100 was decreased in H2O2-induced human umbilical vein endothelial cells. Overexpression of miR-100 attenuated inflammatory response and cell apoptosis in H2O2-induced human umbilical vein endothelial cells. The overexpression of miR-100 inhibited matrix metalloproteinase-9 expression in H2O2-induced human umbilical vein endothelial cells. miR-100 inhibited H2O2-induced human umbilical vein endothelial cell inflammation, oxidative stress, and cell apoptosis via inactivation of Notch signaling by targeting matrix metalloproteinase. Our study demonstrated that miR-100 reduced the inflammatory damage and apoptosis of H2O2-induced human umbilical vein endothelial cells via inactivation of Notch signaling by targeting matrix metalloproteinase. These findings suggested that miR-100 might be a novel therapeutic target for the prevention of thromboangiitis obliterans.
2021-12-23 | Thromboangiitis obliterans plasma-derived exosomal miR-223-5p inhibits cell viability and promotes cell apoptosis of human vascular smooth muscle cells by targeting VCAM1.
Background: Exosomes-encapsulated microRNAs (miRNAs) have been established to be implicated in the pathogenesis of different diseases. Nevertheless, circulating exosomal miRNAs of thromboangiitis obliterans (TAO) remains poorly understood. This study aimed to explore the effects of exosomal miRNAs associated with TAO on human vascular smooth muscle cells (HVSMCs).Methods: The exosomes were isolated from the plasma of TAO patients and normal controls and then were sent for small RNA sequencing. Differentially expressed miRNAs (DE-miRNAs) were identified by bioinformatics analysis and were confirmed by RT-qPCR. After that, PKH67 staining was used to label exosomes and co-cultured with HVSMCs. Cell viability and apoptosis were, respectively, tested by CCK-8 assay and flow cytometry. Finally, dual-luciferase reporter assay was used to confirm the downstream targets of miR-223-5p.Results: A total of 39 DE-miRNAs were identified between TAO patients and normal controls, of which, miR-223-5p was one of the most significantly up-regulated miRNAs. TAO plasma-derived exosomes or miR-223-5p mimics inhibited cell viability of HVSMCs and promoted cell apoptosis. The pro-apoptotic effect of TAO plasma-derived exosomes was alleviated by miR-223-5p inhibitor. Additionally, the expressions of VCAM1 and IGF1R were down-regulated by exosomes and miR-223-5p mimics, and were abrogated by miR-223-5p inhibitor. Dual-luciferase report showed that VCAM1 was the target of miR-223-5p.Conclusions: Our findings imply that circulating exosomal miR-223-5p may play an essential role in the pathogenesis of TAO, and provide a basis for miR-6515-5p/VCAM1 as novel therapeutic targets and pathways for TAO treatment.
2021-06-24 | MiR-223 alleviates thrombus and inflammation in thromboangiitis obliterans rats by regulating NLRP3.
The aim of this study was to observe the regulatory effects of micro ribonucleic acid (miR)-223 on thromboangiitis obliterans (TAO) rats, and to explore the potential regulatory mechanism. Online database TargetScan was used to predict the downstream regulatory targets of miR-223. A total of 45 Sprague Dawley (SD) rats were randomly divided into three groups, including sham operation group (Sham group), Model group, and miR-223 agonist group (miR-223 mimic group). TAO model was successfully established in rats through the injection of lauric acid via the femoral artery. The content of serum thromboxane B2 (TXB2) and endothelin (ET) was measured via enzyme-linked immunosorbent assay (ELISA). The pathological changes in the left hind limb were detected via hematoxylin-eosin (HE) staining. Moreover, the expressions of interleukin-6 (IL-6) and IL-1β in the tissues of the rat left hind limb were determined via immunohistochemistry. In addition, the protein expression of Nod-like receptor protein 3 (NLRP3) in tissues was determined using Western blotting. TargetScan database predicted that NLRP3 was the downstream target gene of miR-223. Compared with the Sham group, Model group exerted significantly higher content of serum TXB2 and ET, severe lesions in the rat left hind limb, as well as significantly increased expressions of IL-6 and IL-1β and protein expression of NLRP3 in tissues of the rat left hind limb (p<0.05). Besides, compared with the Model group, miR-223 mimic group showed remarkably lower content of serum TXB2 and ET, improved lesions in the rat left hind limb, as well as decreased expressions of IL-6 and IL-1β and protein expression of NLRP3 in the tissues of the rat left hind limb (p<0.05). MiR-223 agonist can alleviate thrombus and inflammatory response in TAO rats. The possible underlying mechanism may be related to targeted regulation on NLRP3 inflammasome expression.
2020-03-27 | Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial
Despite the important role that the growth hormone (GH)/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium is considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effects, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy is described. All the elements that trigger the local and systemic production of GH/IGF-I, as well as their possible roles both in physiological and pathological conditions are analyzed. All of the evidence is combined with important data from the GHAS trial, in which GH or a placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of ischemic disease.
2019-05-28 | Alleviation of A disintegrin and metalloprotease 10 (ADAM10) on thromboangiitis obliterans involves the HMGB1/RAGE/ NF-κB pathway.
Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a nonatherosclerotic inflammatory disease that influences medium- and small-sized blood vessels of extremities. However, mechanisms underlying TAO are still unclear. As a mediator associated with inflammation, A disintegrin and metalloprotease 10 (ADAM10) was hypothesized to play inhibitory roles in the development of TAO. Thus, the objective of this study is to investigate the effects of ADAM10 in a sodium laurate-induced TAO rat model and elucidate underlying mechanisms. Male Wistar rats were randomly divided into four groups (n = 6) for treatment: sham-operated (SHAM), TAO model (TAO), ADAM10 low dose injection (3 mg/kg; ADAM10-LD) and ADAM10 high dose injection (6 mg/kg; ADAM10-HD). After 14-day treatment, color Doppler ultrasound and hematology analysis indicated TAO rats displayed higher whole blood viscosity and blood platelet count compared with those in the SHAM group. Histologic evaluation and transmission electron microscopy revealed that the ultrastructural damages of vascular smooth muscle and endothelial cells were observed in TAO rats, such as fractured endoplasmic reticulum, decreased cell counts, and fibrillation. On the other hand, the typical signs and symptoms of TAO rats were significantly alleviated via ADAM10 treatment with a dose-dependent pattern. Real-time PCR and western blot results revealed that the expression of high-mobility-group box 1 (HMGB1), receptor for advanced glycation end-products (RAGE) and nuclear factor-kappa B (NF-κB) increased in TAO rats whereas decreased by ADAM10 treatment in both mRNA and protein levels. In conclusion, the results suggest ADAM10 alleviates symptoms of sodium laurate-induced TAO in rats via the RAGE/NF-κB signaling pathway and provides insight into the molecular basis and a potential therapeutic strategy for TAO.
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Drug Discovery Landscape
12 orphan drug designations for Buerger disease.
12 orphan drug designations for Buerger disease.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
circular RNA therapy expressing Hepatocyte Growth Factor | RNAs | FDA | 2025-10-23 | — | Shanghai CirCode Biomed Co., Ltd. |
Granulocyte colony-stimulating-factor (G-CSF) | proteins | FDA | 2022-06-03 | — | Vasogenesis Inc |
E-selectin/Adeno-Associated Virus (E-sel/AAV2) Gene Therapy | gene therapies | FDA | 2021-10-12 | — | Ambulero Inc |
GCSF-mobilized autologous CD34 cells for intramuscular injection | cell therapies | FDA | 2021-03-04 | — | Lisata Therapeutics |
fully human nicotine-specific monoclonal antibody | antibodies | FDA | 2018-08-22 | — | Antidote Therapeutics, Inc. |
Autologous adipose tissue-derived mesenchymal stem cells [VascoStem] | cell therapies | EMA | 2017-03-20 | — | SPC GmbH |
autologous adipose tissue derived mesenchymal stem cells | cell therapies | FDA | 2016-05-04 | — | Biostar Stem Cell Research Institute |
Adult human bone-marrow-derived, ex-vivo-expanded, pooled allogeneic mesenchymal stromal cells | cell therapies | EMA | 2015-05-21 | — | Voisin Consulting Life Sciences |
allogeneic ex-vivo expanded placental adherent stromal cells | cell therapies | FDA | 2011-08-22 | — | Pluri Biotech Ltd. |
Autologous bone marrow-derived mononuclear cell fraction | cell therapies | EMA | 2010-09-20 | — | t2cure GmbH |
Bone marrow-derived mononuclear cells | cell therapies | FDA | 2010-05-17 | — | t2cure GmbH |
pVGI.1(VEGF2) | gene therapies | FDA | 1999-11-09 | — | Corautus Genetics, Inc. |
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