The new generation of beta-cells: replication, stem cell differentiation, and the role of small molecules.
The new generation of beta-cells: replication, stem cell differentiation, and the role of small molecules.
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DOI：
10.1900/rds.2010.7.93
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发表时间：
2010-01-01
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影响因子：
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通讯作者：
Borowiak, Malgorzata
中科院分区：
文献类型：
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作者：
Borowiak, Malgorzata
糖尿病患者会失去分泌胰岛素的β细胞，或者是不正常工作的β细胞群。由于糖尿病在世界各地的流行程度越来越高，迫切需要一种可再生的细胞来源来取代胰岛β细胞。近年来，已经开发了几种有希望的方法来产生新的β细胞。这包括定向分化多能细胞，如胚胎干细胞(ES)或诱导多能干细胞(IPS)，或对成熟组织细胞重新编程。使用生长因子和小分子已经建立了将细胞群体分化为β细胞、最终内胚层和胰腺前体细胞的高产量方法。然而，定向分化以产生足够数量的功能成熟的β细胞的最后一步尚未在体外实现。除了移植医学的需要外，从研究糖尿病发病机制和寻求替代疗法的平台来看，可再生的β细胞来源也将是重要的。最后，通过产生新的β细胞，我们可以了解更多关于胰腺发育和β细胞规格的细节。这篇综述从干细胞分化的角度对胰腺的个体发生进行了综述，并强调了小分子在生成可再生的β细胞源中的关键方面。此外，它还讨论了迈向糖尿病治疗目标的长期挑战和机遇。
Diabetic patients suffer from the loss of insulin-secreting beta-cells, or from an improper working beta-cell mass. Due to the increasing prevalence of diabetes across the world, there is a compelling need for a renewable source of cells that could replace pancreatic beta-cells. In recent years, several promising approaches to the generation of new beta-cells have been developed. These include directed differentiation of pluripotent cells such as embryonic stem (ES) cells or induced pluripotent stem (iPS) cells, or reprogramming of mature tissue cells. High yield methods to differentiate cell populations into beta-cells, definitive endoderm, and pancreatic progenitors, have been established using growth factors and small molecules. However, the final step of directed differentiation to generate functional, mature beta-cells in sufficient quantities has yet to be achieved in vitro. Beside the needs of transplantation medicine, a renewable source of beta-cells would also be important in terms of a platform to study the pathogenesis of diabetes, and to seek alternative treatments. Finally, by generating new beta-cells, we could learn more details about pancreatic development and beta-cell specification. This review gives an overview of pancreas ontogenesis in the perspective of stem cell differentiation, and highlights the critical aspects of small molecules in the generation of a renewable beta-cell source. Also, it discusses longer term challenges and opportunities in moving towards a therapeutic goal for diabetes.