Department of Pediatrics, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
Clinical Research Centre, Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, China.
Stem Cell Res Ther. 2022 Sep 5;13(1):451. doi: 10.1186/s13287-022-03143-0.
Diabetic foot ulcer (DFU) is a serious chronic complication of diabetes mellitus that contributes to 85% of nontraumatic lower extremity amputations in diabetic patients. Preliminary clinical benefits have been shown in treatments based on mesenchymal stem cells for patients with DFU or peripheral arterial disease (PAD). However, the long-term safety and benefits are unclear for patients with both DFU and PAD who are not amenable to surgical revascularization.
In this phase I pilot study, 14 patients with PAD and incurable DFU were enrolled to assess the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) administration based on conservative treatments. All patients received topical and intravenous administrations of hUC-MSCs at a dosage of 2 × 10 cells/kg with an upper limit of 1 × 10 cells for each dose. The adverse events during treatment and follow-up were documented for safety assessments. The therapeutic efficacy was assessed by ulcer healing status, recurrence rate, and 3-year amputation-free rate in the follow-up phase.
The safety profiles were favorable. Only 2 cases of transient fever were observed within 3 days after transfusion and considered possibly related to hUC-MSC administration intravenously. Ulcer disclosure was achieved for more than 95% of the lesion area for all patients within 1.5 months after treatment. The symptoms of chronic limb ischaemia were alleviated along with a decrease in Wagner scores, Rutherford grades, and visual analogue scale scores. No direct evidence was observed to indicate the alleviation of the obstruction in the main vessels of target limbs based on computed tomography angiography. The duration of rehospitalization for DFU was 2.0 ± 0.6 years. All of the patients survived without amputation due to the recurrence of DFU within 3 years after treatments.
Based on the current pilot study, the preliminary clinical benefits of hUC-MSCs on DFU healing were shown, including good tolerance, a shortened healing time to 1.5 months and a favorable 3-year amputation-free survival rate. The clinical evidence in the current study suggested a further phase I/II study with a larger patient population and a more rigorous design to explore the efficacy and mechanism of hUC-MSCs on DFU healing.
The current study was registered retrospectively on 22 Jan 2022 with the Chinese Clinical Trial Registry (ChiCTR2200055885), http://www.chictr.org.cn/showproj.aspx?proj=135888.
糖尿病足溃疡（DFU）是糖尿病的一种严重慢性并发症，占糖尿病患者非创伤性下肢截肢的 85%。基于间充质干细胞的治疗方法已初步显示出对 DFU 或外周动脉疾病（PAD）患者的临床益处。然而，对于不适合手术血运重建的同时患有 DFU 和 PAD 的患者，其长期安全性和益处尚不清楚。
在这项 I 期试点研究中，纳入了 14 名患有 PAD 和不可治愈的 DFU 的患者，以评估基于保守治疗的人脐带间充质干细胞（hUC-MSC）给药的安全性和疗效。所有患者均接受 hUC-MSC 的局部和静脉给药，剂量为 2×106 细胞/kg，每个剂量的上限为 1×106 细胞。记录治疗和随访期间的不良事件以进行安全性评估。在随访阶段，通过溃疡愈合情况、复发率和 3 年无截肢率评估治疗效果。
安全性特征良好。仅在输注后 3 天内观察到 2 例短暂发热，认为可能与静脉内给予 hUC-MSC 有关。所有患者在治疗后 1.5 个月内，病变区域的溃疡显露面积均超过 95%。慢性肢体缺血症状得到缓解，Wagner 评分、Rutherford 分级和视觉模拟评分均降低。基于计算机断层血管造影术，未观察到直接证据表明目标肢体主要血管阻塞得到缓解。DFU 的再住院时间为 2.0±0.6 年。所有患者均未因治疗后 3 年内 DFU 复发而截肢存活。
基于当前的试点研究，hUC-MSC 对 DFU 愈合的初步临床益处已得到证实，包括良好的耐受性、愈合时间缩短至 1.5 个月和 3 年无截肢生存率良好。当前研究中的临床证据表明，需要进一步开展更大患者人群和更严格设计的 I/II 期研究，以探索 hUC-MSC 对 DFU 愈合的疗效和机制。
本研究于 2022 年 1 月 22 日在中国临床试验注册中心（ChiCTR2200055885）进行了回顾性注册，网址为 http://www.chictr.org.cn/showproj.aspx?proj=135888。
