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首页> 外文期刊>Folia histochemica et cytobiologica >In vitro generation of pancreatic beta-cells for diabetes treatment. I. beta-like cells derived from human pluripotent stem cells
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In vitro generation of pancreatic beta-cells for diabetes treatment. I. beta-like cells derived from human pluripotent stem cells

机译：体外产生糖尿病治疗的胰腺β细胞。 I.β样细胞衍生自人多能干细胞

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摘要

Diabetes mellitus is a chronic disease that affects hundreds of millions of people worldwide. Type 1 diabetes (T1D) is characterized by the lack of pancreatic beta-cells that had been destroyed as a result of an autoimmune response. Therefore, in patients with T1D, the replacement therapy with functional beta-cells derived from extrinsic sources could be a preferable option as compared to insulin treatment. Unfortunately, successful transplantation of whole pancreata or pancreatic islets into patients with diabetes is available only to a fraction of them due to the scarcity of donors. The rapid development of cell reprogramming methods made it possible to generate large numbers of human beta-like cells derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs). This review describes the basis of in vitro differentiaton protocols of beta-like cells that mimic changes of the main signaling pathways during the key stages of human and murine pancreas development, which are described first. During the last 15 years it was found that there are no important differences between hESCs and hiPSCs in their differentiation capacities into beta-like cells and the expression profiles of the key transcription factors. The in vitro produced beta-like cells are immature as demonstrated by functional tests in rodents and single-cell transcriptomic and proteomic analyses. After the transplantation of the beta cell progenitors into immunocompromised diabetic mice, a few weeks have to pass before the increased insulin levels in response to glucose load appear. There is a continuous progress in the development of open-type encapsulation devices which allow the vascularization of the transplanted cells and protect them against host's immune cells. The results of the first clinical trial of human partially differentiated endocrine progenitors of beta cells transplanted into patients with T1D will be published in the year 2019. It is hoped that further improvements in the techniques of large-scale generation of the beta-like cells derived from human pluripotent stem cells will bring us closer to their clinical application as a form of cause-directed therapy for people with diabetes.
机译：糖尿病糖尿病是一种慢性疾病，影响全球数亿人。 1型糖尿病（T1D）的特征在于由于自身免疫反应而缺乏被破坏的胰腺β细胞。因此，在T1D患者中，与胰岛素治疗相比，衍生自外出来源的功能β细胞的替代疗法可能是优选的选择。遗憾的是，由于捐献者的稀缺性，将整个胰腺或胰岛患者的成功移植到糖尿病患者中仅适用于它们的一小部分。细胞重编程方法的快速发展使得可以产生衍生自人胚胎干细胞（HESC）或人诱导的多能干细胞（HIPSC）的大量人β样细胞。该综述描述了β样细胞体外不同协议的基础，其在人和鼠胰腺发育的关键阶段中模仿主要信号通路的变化，这首先描述。在过去的15年中，发现HESC和HIPSC在其分化能力中没有重要差异，进入β样细胞和关键转录因子的表达谱。通过啮齿动物和单细胞转录组和蛋白质组学分析的功能试验证明，体外产生的β样细胞是不成熟的。在将β细胞祖细胞移植到免疫糖尿病小鼠中后，几周必须在增加胰岛素水平响应葡萄糖载荷之前通过。在开放式封装装置的开发中存在持续进展，其允许移植的细胞的血管化并保护它们免受宿主的免疫细胞。 2019年将公布移植到T1D患者的β细胞的第一次临床试验的临床试验。希望进一步改善衍生的大规模产生的大规模产生的技术来自人类多能干细胞将使我们更接近他们的临床应用，作为糖尿病患者的成因治疗。

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