Sequential intravenous allogeneic mesenchymal stromal cells as a potential treatment for thromboangiitis obliterans (Buerger\u2019s disease)

Jorge D Martin-Rufino,Alba M Redondo,Rafael Fernandez-Samos,Eva M Villaron,Raquel Rueda,Fermin Sanchez-Guijo,Francisco S Lozano

doi:10.1186/s13287-018-0901-6

Abstract

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.

Highlights

Thromboangiitis obliterans (TAO), known as Buerger’s disease, is an inflammatory occlusive disorder that affects small and medium sized peripheral blood vessels of the extremities. It is characterized by hypercellular inflammatory thrombotic occlusions of arteries and veins, which leads to vascular insufficiency, critical limb ischemia, and amputation [1]
No adverse effects or signs of allograft rejection were detected following any of the four intravenous allogeneic mesenchymal stromal cells (MSC) infusions
It has been proposed that smoking, the main risk factor of the disease, could induce IL-33-mediated immune responses that would result in vascular endothelial damage with subsequent thrombosis and ischemia [3]

Summary

Introduction

Thromboangiitis obliterans (TAO), known as Buerger’s disease, is an inflammatory occlusive disorder that affects small and medium sized peripheral blood vessels of the extremities. It is characterized by hypercellular inflammatory thrombotic occlusions of arteries and veins, which leads to vascular insufficiency, critical limb ischemia, and amputation [1]. This high-morbidity disease mainly affects young male smokers, severely limiting their quality of life. Several reports have provided insights into the immunopathogenesis of TAO, suggesting that the immune system plays a critical role in the etiology of the disease [1, 3,4,5]

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