间充质干细胞移植治疗新诊断 1 型糖尿病患者：一项 I/II 期随机安慰剂对照临床试验。

Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial.

机构信息

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Advanced Therapy Medicinal Product Technology Development Center (ATMP-TDC), Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

出版信息

Stem Cell Res Ther. 2022 Jun 20;13(1):264. doi: 10.1186/s13287-022-02941-w.

BACKGROUND

Type-1 diabetes (T1D) occurs following autoimmune-induced pancreatic beta cells death. Among several treatment modalities, mesenchymal stem cells (MSCs) transplantation is promising for autoimmune disorders due to immunomodulation, regeneration, and migration to damaged tissue upon systemic injection. This study assessed the safety and efficacy of intravenous injection of autologous bone marrow-derived MSCs in newly diagnosed T1D patients.

METHODS

After receiving informed consent, 21 patients who met the study criteria were enrolled and randomly assigned to receive either MSCs or placebo. Each patient in the experimental group received two doses of MSCs and was followed for at least one-year post-transplantation.

RESULTS

The results have shown that this transplantation is safe and significantly reduces the number of hypoglycemic episodes. MSCs transplantation improved glycated hemoglobin (HbA1c), shifted serum cytokine patterns from pro-inflammatory to anti-inflammatory, increased the number of regulatory T-cells in the peripheral blood, and improved quality of life. Early transplantation of MSCs significantly improved HbA1c and C-peptide levels and shifted pro-inflammatory cytokines to anti-inflammatory cytokines. Also, exercise combined with MSCs transplantation improved glycemic and immunologic indices.

CONCLUSIONS

Taken together, autologous MSC transplantation is safe and effective, and its early transplantation is a promising treatment in newly diagnosed T1D children suffering from hypoglycemic episodes.

TRIAL REGISTRATION

This clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the identifier IRCT ID: IRCT2016070428786N1 registered on August 20, 2016 (Retrospectively registered) ( https://en.irct.ir/trial/23256 ) and at the U.S. National Institutes of Health (ClinicalTrials.gov) with the related identifier NCT04078308 registered on September 6, 2019 (Retrospectively registered). ( https://clinicaltrials.gov/ct2/show/NCT04078308 ).

背景

1 型糖尿病（T1D）发生在自身免疫引起的胰岛β细胞死亡之后。在几种治疗方式中，间充质干细胞（MSCs）移植由于其免疫调节、再生和向受损组织迁移的特性，对于自身免疫性疾病具有很大的应用前景。本研究评估了静脉注射自体骨髓来源的间充质干细胞在新诊断的 T1D 患者中的安全性和疗效。

方法

在获得知情同意后，符合研究标准的 21 名患者被纳入并随机分配接受 MSCs 或安慰剂治疗。实验组的每位患者接受两次 MSCs 治疗，并在移植后至少随访一年。

结果

结果表明，这种移植是安全的，并能显著减少低血糖发作的次数。MSCs 移植改善了糖化血红蛋白（HbA1c），使血清细胞因子谱从促炎转向抗炎，增加了外周血中调节性 T 细胞的数量，并改善了生活质量。早期移植 MSCs 可显著改善 HbA1c 和 C 肽水平，并将促炎细胞因子转为抗炎细胞因子。此外，运动与 MSCs 移植相结合可改善血糖和免疫指标。