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Sequential intravenous allogeneic mesenchymal stromal cells as a potential treatment for thromboangiitis obliterans (Buerger’s disease)

机译:顺序静脉同种异体间充质基质细胞可治疗闭塞性血栓血管炎(Buerger病)

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摘要

Thromboangiitis obliterans (TAO), also known as Buerger’s Disease, is an occlusive vasculitis linked with high morbidity and amputation risk. To date, TAO is deemed incurable due to the lack of a definitive treatment. The immune system and inflammation are proposed to play a central role in TAO pathogenesis. Due to their immunomodulatory effects, mesenchymal stromal cells (MSCs) are the subject of intense research for the treatment of a wide range of immune-mediated diseases. Thus far, local intramuscular injections of autologous or allogeneic MSCs have shown promising results in TAO. However, sequential intravenous allogeneic MSC administration has not yet been explored, which we hypothesized could exert a systemic anti-inflammatory effect in the vasculature and modulate the immune response. Here, we report the first case of a TAO patient at amputation risk treated with four sequential intravenous infusions of bone marrow-derived allogeneic MSCs from a healthy donor. Following administration, there was significant regression of foot skin ulcers and improvements in rest pain, Walking Impairment Questionnaire scores, and quality of life. Sixteen months after the infusion, the patient had not required any further amputations. This report highlights the potential of sequential allogeneic MSC infusions as an effective treatment for TAO, warranting further studies to compare this approach with the more conventionally used intramuscular MSC administration and other cell-based therapies.
机译:血栓闭塞性血管炎(TAO),也称为Buerger病,是一种闭塞性血管炎,与高发病率和截肢风险相关。迄今为止,由于缺乏确定的治疗方法,TAO被认为是无法治愈的。有人认为免疫系统和炎症在TAO发病机理中起着核心作用。由于其免疫调节作用,间充质基质细胞(MSCs)是治疗广泛的免疫介导疾病的研究重点。迄今为止,自体或同种异体MSC的局部肌内注射已在TAO中显示出令人鼓舞的结果。然而,尚未探索过顺序静脉内异源MSC的给药方法,我们假设它可以在脉管系统中发挥全身性抗炎作用并调节免疫反应。在这里,我们报道了第一例一名有截肢风险的TAO患者,接受了四次连续静脉输注来自健康捐献者的骨髓来源的同种异体MSC。给药后,足部皮肤溃疡明显消退,休息疼痛,步行障碍问卷得分和生活质量得到改善。输液后十六个月,患者不再需要截肢。该报告强调了异基因MSC连续输注作为TAO的有效治疗方法的潜力,值得进一步研究以将该方法与更常规的肌内MSC给药和其他基于细胞的疗法进行比较。

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