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Small molecule regulation of stem cells that generate bone, chondrocyte, and cardiac cells.
Current Topics in Medicinal Chemistry ( IF 3.4 ) Pub Date : 2020-09-30 , DOI: 10.2174/1568026620666200820143912
John R Cashman 1
Affiliation  

Embryonic stem cells (ESCs) are stem cells (SCs) that can self-renew and differentiate into a myriad of cell types. The process of developing stemness is determined by signaling molecules that drive stem cells to a specific lineage. For example, ESCs can differentiate into mature cells (e.g., cardiomyocytes) and mature cardiomyocytes can be characterized for cell beating, action potential, and ion channel function. A goal of this Perspective is to show how small molecules can be used to differentiate ESCs into cardiomyocytes and how this can reveal novel aspects of SC biology. This approach can also lead to the discovery of new molecules of use in cardiovascular disease.

Human induced pluripotent stem cells (hiPSCs) afford the ability to produce unlimited numbers of normal human cells. The creation of patient-specific hiPSCs provides an opportunity to study cell models of human disease. The second goal is to show that small molecules can stimulate hiPSC commitment to cardiomyocytes. How iPSCs can be used in an approach to discover new molecules of use in cardiovascular disease will also be shown in this study.

Adult SCs, including mesenchymal stem cells (MSCs), can likewise participate in self-renewal and multilineage differentiation. MSCs are capable of differentiating into osteoblasts, adipocytes or chondrocytes. A third goal of this Perspective is to describe differentiation of MSCs into chondrogenic and osteogenic lineages. Small molecules can stimulate MSCs to specific cell fate both in vitro and in vivo. In this Perspective, some recent examples of applying small molecules for osteogenic and chondrogenic cell fate determination are summarized. Underlying molecular mechanisms and signaling pathways involved are described. Small molecule-based modulation of stem cells shows insight into cell regulation and potential approaches to therapeutic strategies for MSC-related diseases.



中文翻译:

干细胞的小分子调节,可产生骨骼,软骨细胞和心脏细胞。

胚胎干细胞(ESC)是可以自我更新并分化为多种细胞类型的干细胞(SC)。形成干细胞的过程是通过将干细胞驱动至特定谱系的信号分子来确定的。例如,ESC可以分化为成熟细胞(例如,心肌细胞),并且可以针对细胞跳动,动作电位和离子通道功能来表征成熟的心肌细胞。该观点的目的是展示如何使用小分子将ESCs分化为心肌细胞,以及如何揭示SC生物学的新方面。这种方法还可以导致发现用于心血管疾病的新分子。

人类诱导的多能干细胞(hiPSC)具有产生无限数量的正常人类细胞的能力。患者特异性hiPSC的创建为研究人类疾病的细胞模型提供了机会。第二个目标是证明小分子可以刺激hiPSC对心肌细胞的反应。这项研究还将展示如何将iPSC用于发现心血管疾病的新分子的方法。

成年SC,包括间充质干细胞(MSC),同样可以参与自我更新和多系分化。MSC能够分化为成骨细胞,脂肪细胞或软骨细胞。该观点的第三个目标是描述MSC分化为成软骨和成骨细胞系。小分子可以在体外和体内刺激MSC达到特定的细胞命运。在此观点中,总结了一些应用小分子测定成骨和软骨细胞命运的最新实例。描述了涉及的基础分子机制和信号传导途径。基于小分子的干细胞调节显示出对细胞调节的了解,以及对MSC相关疾病的治疗策略的潜在方法。

更新日期:2020-11-03
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