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比较人诱导多能干细胞和间充质干细胞在 2D 和 3D 体外培养系统中向胰岛素分泌细胞分化的潜能。

Comparison of human-induced pluripotent stem cells and mesenchymal stem cell differentiation potential to insulin producing cells in 2D and 3D culture systems in vitro.

机构信息

Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.

Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.

出版信息

J Cell Physiol. 2020 May;235(5):4239-4246. doi: 10.1002/jcp.29298. Epub 2019 Oct 15.

Abstract

Diabetes is one of the most common diseases in the world that is chronic, progressive, and costly, and causes many complications. Common drug therapies are not able to cure it, and pancreas transplantation is not responsive to the high number of patients. The production of the insulin producing cells (IPCs) from the stem cells in the laboratory and their transplantation to the patient's body is one of the most promising new approaches. In this study, the differentiation potential of the induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) into IPCs was compared to each other while cultured on poly(lactic-co-glycolic) acid (PLGA)/polyethylene glycol (PEG) nanofibrous scaffold as a 3D substrate and tissue culture polystyrene (TCPS) as a 2D substrate. Although the expression level of the insulin, Glut2 and pdx-1 genes in stem cells cultured on 3D substrate was significantly higher than the stem cells cultured on 2D substrate, the highest expression level of these genes was detected in the iPSCs cultured on PLGA-PEG. Insulin and C-peptide secretions from differentiated cells were also investigated and the results showed that secretions in cultured iPSCs on the PLGA-PEG were significantly higher than cultured iPSCs on the TCPS and cultured MSCs on both PLGA-PEG and TCPS. In addition, insulin protein was also expressed in the cultured iPSCs on the PLGA-PEG significantly higher than cultured MSCs on the PLGA-PEG. It can be concluded that differentiation potential of iPSCs into IPCs is significantly higher than human MSCs at both 2D and 3D culture systems.

摘要

糖尿病是世界上最常见的疾病之一,具有慢性、进行性和高成本的特点,并会导致许多并发症。常见的药物治疗方法无法治愈它,而胰腺移植也无法满足大量患者的需求。从实验室中的干细胞中产生胰岛素产生细胞(IPCs)并将其移植到患者体内是最有前途的新方法之一。在这项研究中,比较了诱导多能干细胞(iPSCs)和间充质干细胞(MSCs)在聚(乳酸-共-乙醇酸)(PLGA)/聚乙二醇(PEG)纳米纤维支架上作为 3D 底物和组织培养聚苯乙烯(TCPS)作为 2D 底物培养时向 IPCs 的分化潜力。尽管在 3D 底物上培养的干细胞中胰岛素、Glut2 和 pdx-1 基因的表达水平明显高于在 2D 底物上培养的干细胞,但在 PLGA-PEG 上培养的 iPSCs 中检测到这些基因的最高表达水平。还研究了分化细胞的胰岛素和 C-肽分泌,结果表明,在 PLGA-PEG 上培养的 iPSCs 分泌的胰岛素和 C-肽明显高于在 TCPS 上培养的 iPSCs 和在 PLGA-PEG 和 TCPS 上培养的 MSCs。此外,在 PLGA-PEG 上培养的 iPSCs 中也表达了胰岛素蛋白,明显高于在 PLGA-PEG 上培养的 MSCs。可以得出结论,iPSCs 向 IPCs 的分化潜力在 2D 和 3D 培养系统中均明显高于人 MSCs。

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