Differentiation of Uc-MSCs into insulin secreting islet-like clusters by trypsin through TGF-beta signaling pathway

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation Pub Date : 2023-12-16 DOI:10.1016/j.diff.2023.100744

Feirong Huang , Jiashuang Lai , Lixia Qian , Wanjin Hong , Liang-cheng Li

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引用次数: 0

Abstract

Differentiation of human umbilical cord mesenchymal stem cells (Uc-MSCs) into islet-like clusters which are capable of synthesizing and secreting insulin can potentially serve as donors for islet transplantation in the patient deficiency in islet β cell function both in type 1 or type 2 diabetic patients. Therefore, we developed an easy and higher efficacy approach by trypsinazing the Uc-MSCs and followed culture in differentiation medium to induce of Uc-MSCs differentiation into islet-like clusters, and the potential mechanism that in the early stage of differentiation was also investigated by using RNA-sequencing and bioinformatics. Results show that induction efficacy was reached to 98% and TGF-β signaling pathway may play critical role in the early stage differentiation, it was further confirmed that the retardant effect of differentiation progress either in cell morphology or in islet specific genes expression can be observed upon blocking the activation of TGF-β signaling pathway using specific inhibitor of LY2109761 (TβRI/II kinase inhibitor). Our current study, for the first time, development a protocol for differentiation of Uc-MSCs into islet-like clusters, and revealed the importance of TGF-β signaling pathway in the early stage of differentiation of Uc-MSCs into islet-like clusters. Our study will provide alternative approach for clinical treatment of either type I or type II diabtes mellitus with dysfunctional pancreatic islets.

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胰蛋白酶通过 TGF-beta 信号通路将 Uc-MSCs 分化成可分泌胰岛素的小岛状集群

将人脐带间充质干细胞（Uc-MSCs）分化成能合成和分泌胰岛素的胰岛样细胞团，有可能作为胰岛移植的供体，用于治疗1型或2型糖尿病患者的胰岛β细胞功能缺陷。因此，我们开发了一种简便、高效的方法，通过胰蛋白酶诱导 Uc-间充质干细胞，然后在分化培养基中培养，诱导 Uc-间充质干细胞分化成胰岛样团，并利用 RNA 序列和生物信息学研究了分化早期的潜在机制。结果表明，TGF-β信号通路在早期分化中可能起着关键作用，诱导效率高达98%，并进一步证实，使用特异性抑制剂LY2109761（TβRI/II激酶抑制剂）阻断TGF-β信号通路的激活后，可在细胞形态或胰岛特异性基因表达方面观察到延缓分化进程的作用。本研究首次提出了将 Uc-MSCs 分化成小岛状细胞簇的方案，并揭示了 TGF-β 信号通路在 Uc-MSCs 分化成小岛状细胞簇早期阶段的重要性。我们的研究将为胰岛功能障碍的I型或II型糖尿病的临床治疗提供另一种方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Differentiation 生物-发育生物学

CiteScore

4.10

自引率

3.40%

发文量

审稿时长

51 days

期刊介绍： Differentiation is a multidisciplinary journal dealing with topics relating to cell differentiation, development, cellular structure and function, and cancer. Differentiation of eukaryotes at the molecular level and the use of transgenic and targeted mutagenesis approaches to problems of differentiation are of particular interest to the journal. The journal will publish full-length articles containing original work in any of these areas. We will also publish reviews and commentaries on topics of current interest. The principal subject areas the journal covers are: • embryonic patterning and organogenesis • human development and congenital malformation • mechanisms of cell lineage commitment • tissue homeostasis and oncogenic transformation • establishment of cellular polarity • stem cell differentiation • cell reprogramming mechanisms • stability of the differentiated state • cell and tissue interactions in vivo and in vitro • signal transduction pathways in development and differentiation • carcinogenesis and cancer • mechanisms involved in cell growth and division especially relating to cancer • differentiation in regeneration and ageing • therapeutic applications of differentiation processes.