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基于间充质干细胞的糖尿病治疗策略中关于收获部位和供体来源的考量

Considerations on the harvesting site and donor derivation for mesenchymal stem cells-based strategies for diabetes.

作者信息

Zazzeroni L, Lanzoni G, Pasquinelli G, Ricordi C

机构信息

Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.

Diabetes Research Institute, University of Miami, Miami, FL, USA.

出版信息

CellR4 Repair Replace Regen Reprogram. 2017;5(5). Epub 2017 Sep 29.

Abstract

Mesenchymal Stem Cells (MSCs) possess important characteristics that could be exploited in therapeutic strategies for Type 1 Diabetes (T1D) and for certain complications of Type 2 Diabetes (T2D). MSCs can inhibit autoimmune, alloimmune and inflammatory processes. Moreover, they can promote the function of endogenous and transplanted pancreatic islets. Furthermore, they can stimulate angiogenesis. MSC functions are largely mediated by their secretome, which includes growth factors, exosomes, and other extracellular vesicles. MSCs have shown a good safety profile in clinical trials. MSC-derived exosomes are emerging as an alternative to the transplantation of live MSCs. MSCs harvested from different anatomical locations (e.g. bone marrow, umbilical cord, placenta, adipose tissue, and pancreas) have shown differences in gene expression profiles and function. Data from clinical trials suggest that umbilical cord-derived MSCs could be superior to bone marrow-derived MSCs for the treatment of T1D. Autologous MSCs from diabetic patients may present abnormal functions. BM-MSCs from T1D patients exhibit gene expression differences that may impact in vivo function. BM-MSCs from T2D patients seem to be significantly impaired due to the T2D diabetic milieu. In this review, we highlight how the harvesting site and donor derivation can affect the efficacy of MSC-based treatments for T1D and T2D.

摘要

间充质干细胞(MSCs)具有一些重要特性,可用于1型糖尿病(T1D)和2型糖尿病(T2D)某些并发症的治疗策略。间充质干细胞可抑制自身免疫、同种免疫和炎症过程。此外,它们可促进内源性和移植胰腺胰岛的功能。而且,它们能刺激血管生成。间充质干细胞的功能很大程度上由其分泌组介导,分泌组包括生长因子、外泌体和其他细胞外囊泡。间充质干细胞在临床试验中显示出良好的安全性。源自间充质干细胞的外泌体正成为活间充质干细胞移植的替代物。从不同解剖位置(如骨髓、脐带、胎盘、脂肪组织和胰腺)获取的间充质干细胞在基因表达谱和功能方面存在差异。临床试验数据表明,脐带源间充质干细胞在治疗T1D方面可能优于骨髓源间充质干细胞。糖尿病患者的自体间充质干细胞可能存在功能异常。T1D患者的骨髓间充质干细胞表现出基因表达差异,这可能影响其体内功能。由于T2D糖尿病环境,T2D患者的骨髓间充质干细胞似乎明显受损。在本综述中,我们强调了采集部位和供体来源如何影响基于间充质干细胞治疗T1D和T2D的疗效。

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