Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Stem Cell Res Ther. 2023 Jul 5;14(1):174. doi: 10.1186/s13287-023-03390-9.
Critical limb ischemia (CLI) is associated with increased risk of tissue loss, leading to significant morbidity and mortality. Therapeutic angiogenesis using cell-based treatments, notably mesenchymal stem cells (MSCs), is essential for enhancing blood flow to ischemic areas in subjects suffering from CLI. The objective of this study was to evaluate the feasibility of using placenta-derived mesenchymal stem cells (P-MSCs) in patients with CLI.
This phase I dose-escalation study investigated P-MSCs in nine CLI patients who were enrolled into each of the two dosage groups (20 × 10 and 60 × 10 cells), delivered intramuscularly twice, two months apart. The incidence of treatment-related adverse events was the primary endpoint. The decrease in inflammatory cytokines, improvement in the ankle-brachial pressure index (ABI), maximum walking distance, vascular collateralization, alleviation of rest pain, healing of ulceration, and avoidance of major amputation in the target leg were the efficacy outcomes.
All dosages of P-MSCs, including the highest tested dose of 60 × 10 cells, were well tolerated. During the 6-month follow-up period, there was a statistically significant decrease in IL-1 and IFN-γ serum levels following P-MSC treatment. The blood lymphocyte profile of participants with CLI did not significantly differ, suggesting that the injection of allogeneic cells did not cause T-cell proliferation in vivo. We found clinically substantial improvement in rest pain, ulcer healing, and maximum walking distance after P-MSC implantation. In patients with CLI, we performed minor amputations rather than major amputations. Angiography was unable to demonstrate new small vessels formation significantly.
The observations from this phase I clinical study indicate that intramuscular administration of P-MSCs is considered safe and well tolerated and may dramatically improve physical performance and minimize inflammatory conditions in patients with CLI.
IRCT, IRCT20210221050446N1. Registered May 09, 2021.
严重肢体缺血（CLI）与组织损失风险增加相关，导致发病率和死亡率显著升高。细胞治疗，特别是间充质干细胞（MSCs）的治疗性血管生成，对于增强 CLI 患者缺血区域的血流至关重要。本研究旨在评估胎盘来源间充质干细胞（P-MSCs）在 CLI 患者中的应用可行性。
这是一项 I 期剂量递增研究，纳入了 9 名 CLI 患者，每位患者均入组了两个剂量组（20×10 和 60×10 个细胞），每个剂量组接受两次肌肉内注射，间隔两个月。治疗相关不良事件的发生率是主要终点。炎症细胞因子的减少、踝肱指数（ABI）的改善、最大步行距离、血管侧支形成、静息痛缓解、溃疡愈合和目标腿避免大截肢是疗效终点。
所有剂量的 P-MSCs 均耐受良好，包括测试的最高剂量 60×10 个细胞。在 6 个月的随访期间，P-MSC 治疗后血清中 IL-1 和 IFN-γ 的水平显著下降。CLI 患者的血液淋巴细胞谱没有显著差异，这表明注射同种异体细胞不会在体内引起 T 细胞增殖。我们发现 P-MSC 植入后静息痛、溃疡愈合和最大步行距离有明显的临床改善。在 CLI 患者中，我们进行了小截肢而非大截肢。血管造影未能显著显示新的小血管形成。
这项 I 期临床研究的结果表明，肌肉内注射 P-MSCs 是安全且耐受良好的，可能显著改善 CLI 患者的身体机能并最大限度地减轻炎症状态。
IRCT，IRCT20210221050446N1。注册于 2021 年 5 月 9 日。
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