Stem cell therapy provides great hope for patients with diabetes mellitus (DM). DM is a seriously alarming metabolic disease characterized by hyperglycemia and β cell dysfunction. Efficient novel therapeutic modalities to treat DM are indeed warranted. Stem cells (SC) derived from the umbilical cord specifically provide several advantages and unique characteristics being a readily available non-invasive source, with an additional credit for their banking potential. This meta-analysis study aims to provide a focused assessment for therapeutic efficacy of umbilical cord (UC)-derived SC-transplantation, namely Wharton’s jelly mesenchymal stem cells (WJ-MSCs) and umbilical cord blood (UCB) for DM. The clinical efficacy was evaluated based on glycemic control status (reflected on HbA1c%) and β cell function (reflected on C-peptide levels), as well as the daily insulin requirement in diabetic patients after receiving UC-derived SC-transplantation compared to baseline values. Moreover, we assessed these outcome measures in patients who received such intervention compared to those who did not receive it in randomized/non-randomized controlled clinical trials. We employed a random-effects model and standardized mean difference for this meta-analysis. Eleven eligible clinical studies were included; WJ-MSCs (6 studies; 172 patients including 71 controls) and UCB (5 studies; 74 patients including 15 controls). WJ-MSCs significantly improved HbA1c% (pooled-estimate − 1.085; 95%CI (− 1.513, − 0.657); p < 0.001) and C-peptide levels (pooled-estimate 1.008; 95%CI (0.475, 1.541); p < 0.001), as well as the daily insulin-requirement (pooled-estimate − 2.027; 95%CI (− 3.32, − 0.733); p = 0.002). On the contrary, UCB was found to be uniformly ineffective; HbA1c% (pooled-estimate − 0.091, 95%CI (− 0.454, 0.271); p = 0.622), significantly deteriorated C-peptide levels (pooled-estimate − 0.789; 95%CI (− 1.252, − 0.325); p < 0.001) and daily insulin-requirement (pooled-estimate 0.916; 95%CI (0.247, 1.585); p = 0.007). All these observations remained consistent when we carried out sub-group meta-analysis for T1DM and T2DM and also when we compared patients who received WJ-MSCs or UCB to controls. The results of our meta-analysis provide a clear evidence for the superior efficacy of WJ-MSCs over UCB in DM. This sheds lights on the importance to consider banking of WJ-MSCs together with the well-established routine UCB-banking, especially for those with family history of DM. Additionally, further clinical studies are required to investigate therapeutic efficacy of selected/enriched UCB-derived cell populations with immunomodulatory/regenerative potential in DM.

中文翻译：

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脐带源干细胞治疗糖尿病的疗效：一项荟萃分析研究


干细胞治疗为糖尿病（DM）患者带来了巨大的希望。 DM是一种严重令人担忧的代谢性疾病，其特征是高血糖和β细胞功能障碍。确实需要有效的新型治疗方式来治疗 DM。源自脐带的干细胞（SC）作为一种容易获得的非侵入性来源，具有多种优势和独特的特性，并且还因其储存潜力而受到额外认可。这项荟萃分析研究旨在重点评估脐带 (UC) 来源的 SC 移植（即沃顿胶间充质干细胞 (WJ-MSC) 和脐带血 (UCB)）对糖尿病的治疗效果。临床疗效的评估基于血糖控制状态（反映在 HbA1c%）和 β 细胞功能（反映在 C 肽水平），以及糖尿病患者接受 UC 衍生 SC 移植后与基线相比的每日胰岛素需求量价值观。此外，我们在随机/非随机对照临床试验中评估了接受此类干预的患者与未接受干预的患者的这些结果指标。我们采用随机效应模型和标准化均值差进行荟萃分析。纳入了十一项符合条件的临床研究； WJ-MSC（6 项研究；172 名患者，包括 71 名对照）和 UCB（5 项研究；74 名患者，包括 15 名对照）。 WJ-MSC 显着改善了 HbA1c%（汇总估计值 − 1.085；95%CI (−1.513，−0.657)；p < 0.001）和 C 肽水平（汇总估计值 1.008；95%CI (0.475，1.541)；p < 0.001），以及每日胰岛素需求量（汇总估计值 - 2.027；95% CI (- 3.32，- 0.733)；p = 0.002）。相反，UCB 被发现毫无效果； HbA1c%（汇总估计值 - 0。091，95%CI（−0.454，​​0.271）； p = 0.622）、C 肽水平显着恶化（汇总估计值 − 0.789；95%CI（−1.252，−0.325）；p < 0.001）和每日胰岛素需求量（汇总估计值 0.916；95%CI（0.247， 1.585）；p = 0.007）。当我们对 T1DM 和 T2DM 进行亚组荟萃分析时，以及当我们将接受 WJ-MSC 或 UCB 的患者与对照组进行比较时，所有这些观察结果仍然一致。我们的荟萃分析结果为 WJ-MSC 治疗 DM 的疗效优于 UCB 提供了明确的证据。这说明了考虑将 WJ-MSC 储存与完善的常规 UCB 储存一起考虑的重要性，特别是对于有 DM 家族史的患者。此外，还需要进一步的临床研究来研究具有免疫调节/再生潜力的选定/富集的 UCB 衍生细胞群对 DM 的治疗功效。