Peripheral artery disease (PAD) affects more than 230 million people worldwide, with approximately 11% of patients presenting with advanced-stage PAD or critical limb ischemia (CLI). To avoid or delay amputation, particularly in no-option CLI patients with infeasible or ineffective revascularization, new treatment strategies such as regenerative therapies should be developed. Mesenchymal stem cells (MSCs) are the most popular cell source in regenerative therapies. They possess significant characteristics such as angiogenic, anti-inflammatory, and immunomodulatory activities, which encourage their application in different diseases. This phase I clinical trial reports the safety, feasibility, and probable efficacy of the intramuscular administration of allogeneic Wharton’s jelly-derived MSCs (WJ-MSCs) in type 2 diabetes patients with CLI. Out of six screened patients with CLI, five patients were administered WJ-MSCs into the gastrocnemius, soleus, and the proximal part of the tibialis anterior muscles of the ischemic lower limb. The safety of WJ-MSCs injection was considered a primary outcome. Secondary endpoints included wound healing, the presence of pulse at the disease site, the absence of amputation, and improvement in visual analogue scale (VAS), pain-free walking time, and foot and ankle disability index (FADI). No patient experienced adverse events and foot or even toe amputation during the 6-month follow-up. Six months after the intervention, there were a significantly lower VAS score and significantly higher pain-free walking time and FADI score than the baseline, but no statistically significant difference was seen between other time points. In conclusion, allogeneic WJ-MSC transplantation in patients with CLI seems to be safe and effective.

外周动脉疾病 (PAD) 影响着全球超过 2.3 亿人，其中约 11% 的患者出现晚期 PAD 或严重肢体缺血 (CLI)。为了避免或延迟截肢，特别是对于血运重建不可行或无效的无选择 CLI 患者，应开发新的治疗策略，例如再生疗法。间充质干细胞（MSC）是再生疗法中最受欢迎的细胞来源。它们具有血管生成、抗炎和免疫调节活性等显着特征，这鼓励它们在不同疾病中的应用。该 I 期临床试验报告了在患有 CLI 的 2 型糖尿病患者中肌肉注射同种异体沃顿胶源性 MSC (WJ-MSC) 的安全性、可行性和可能疗效。在 6 名筛选的 CLI 患者中，有 5 名患者被注射到缺血下肢的腓肠肌、比目鱼肌和胫骨前肌近端部分。 WJ-MSC 注射的安全性被认为是主要结果。次要终点包括伤口愈合、疾病部位有脉搏、没有截肢、视觉模拟评分（VAS）的改善、无痛步行时间以及足踝残疾指数（FADI）。在 6 个月的随访期间，没有患者出现不良事件和足部甚至脚趾截肢。干预六个月后，与基线相比，VAS 评分显着降低，无痛步行时间和 FADI 评分显着升高，但其他时间点之间没有统计学上的显着差异。总之，CLI 患者的同种异体 WJ-MSC 移植似乎是安全有效的。