Banco Multitejidos y Centro de Terapias Avanzadas, Clínica FOSCAL Internacional, 681004, Floridablanca, Colombia.
Fundación Oftalmológica de Santander Carlos Ardila Lulle, 681004, Floridablanca, Colombia.
Stem Cell Res Ther. 2023 Aug 25;14(1):221. doi: 10.1186/s13287-023-03427-z.
Chronic limb-threatening ischemia (CLTI) represents the final stage of peripheral arterial disease. Approximately one-third of patients with CLTI are not eligible for conventional surgical treatments. Furthermore, patients with advanced stage of CLTI are prone to amputation and death. Thus, an effective therapeutic strategy is urgently needed. In this context, autologous bone marrow mononuclear cell (auto-BM-MNC) and allogeneic mesenchymal stem cells represent a promising therapeutic approach for treating CLTI. In this study, we compared the safety and beneficial therapeutic effect of auto-BM-MNC versus allogeneic Wharton jelly-derived mesenchymal stem cells (allo-WJ-MSCs) in diabetic patients with CLTI.
We performed a randomized, prospective, double-blind and controlled pilot study. Twenty-four diabetic patients in the advanced stage of CLTI (4 or 5 in Rutherford's classification) and a transcutaneous oxygen pressure (TcPO) below 30 mmHg were randomized to receive 15 injections of (i) auto-BM-MNC (7.197 × 10 ± 2.984 × 10 cells/mL) (n = 7), (ii) allo-WJ-MSCs (1.333 × 10 cells/mL) (n = 7) or (iii) placebo solution (1 mL) (n = 10), which were administered into the periadventitial layer of the arterial walls under eco-Doppler guidance. The follow-up visits were at months 1, 3, 6, and 12 to evaluate the following parameters: (i) Rutherford's classification, (ii) TcPO, (iii) percentage of wound closure, (iv) pain, (v) pain-free walking distance, (vi) revascularization and limb-survival proportion, and (vii) life quality (EQ-5D questionnaire).
No adverse events were reported. Patients with CLTI who received auto-BM-MNC and allo-WJ-MSCs presented an improvement in Rutherford's classification, a significant increase in TcPO values, a reduction in the lesion size in a shorter time, a decrease in the pain score and an increase in the pain-free walking distance, in comparison with the placebo group. In addition, the participants treated with auto-BM-MNC and allo-WJ-MSCs kept their limbs during the follow-up period, unlike the placebo group, which had a marked increase in amputation.
Our results showed that patients with CLTI treated with auto-BM-MNC and allo-WJ-MSCs conserved 100% of their limb during 12 months of the follow-up compared to the placebo group, where 60% of participants underwent limb amputation in different times. Furthermore, we observed a faster improvement in the allo-WJ-MSC group, unlike the auto-BM-MNC group. Trial registration This study was retrospectively registered at ClinicalTrials.gov (NCT05631444).
慢性肢体威胁性缺血（CLTI）代表外周动脉疾病的终末阶段。大约三分之一的 CLTI 患者不符合传统手术治疗的条件。此外，CLTI 晚期患者易截肢和死亡。因此，迫切需要有效的治疗策略。在这种情况下，自体骨髓单核细胞（auto-BM-MNC）和同种异体间充质干细胞代表了治疗 CLTI 的一种有前途的治疗方法。在本研究中，我们比较了自体 BM-MNC 与同种异体 Wharton 果冻衍生间充质干细胞（allo-WJ-MSCs）在糖尿病合并 CLTI 患者中的安全性和有益治疗效果。
我们进行了一项随机、前瞻性、双盲和对照的初步研究。24 例糖尿病 CLTI 晚期患者（Rutherford 分类 4 或 5 级）和经皮氧分压（TcPO）低于 30mmHg 的患者随机接受 15 次以下治疗：（i）自体 BM-MNC（7.197×10±2.984×10 个细胞/mL）（n=7）、（ii）allo-WJ-MSCs（1.333×10 个细胞/mL）（n=7）或（iii）安慰剂溶液（1mL）（n=10），在 eco-Doppler 引导下注入动脉壁的外膜层。随访时间为 1、3、6 和 12 个月，以评估以下参数：（i）Rutherford 分类，（ii）TcPO，（iii）伤口闭合百分比，（iv）疼痛，（v）无痛行走距离，（vi）再血管化和肢体存活率比例，以及（vii）生活质量（EQ-5D 问卷）。
未报告不良事件。接受自体 BM-MNC 和 allo-WJ-MSCs 治疗的 CLTI 患者的 Rutherford 分类得到改善，TcPO 值显著增加，病变大小在更短的时间内缩小，疼痛评分降低，无痛行走距离增加，与安慰剂组相比。此外，与安慰剂组相比，接受自体 BM-MNC 和 allo-WJ-MSCs 治疗的患者在随访期间保留了肢体，而安慰剂组的截肢率明显增加。
我们的结果表明，与安慰剂组相比，接受自体 BM-MNC 和 allo-WJ-MSCs 治疗的 CLTI 患者在 12 个月的随访中 100%保留了肢体，而安慰剂组中有 60%的患者在不同时间进行了截肢。此外，我们观察到 allo-WJ-MSC 组的改善速度更快，而自体 BM-MNC 组则不然。
本研究在 ClinicalTrials.gov（NCT05631444）上进行了回顾性注册。
