A chemical genetics approach for specific differentiation of stem cells to somatic cells: A new promising therapeutical approach
A chemical genetics approach for specific differentiation of stem cells to somatic cells: A new promising therapeutical approach
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DOI：
10.2174/138620708783398322
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发表时间：
2008-01-01
影响因子：
1.8
通讯作者：
Hescheler, Juergen
中科院分区：
文献类型：
--
作者：
Sachinidis, Agapios;Sotiriadou, Isaia;Hescheler, Juergen
通过移植由胚胎干（ES）细胞产生的体细胞对严重退行性疾病如糖尿病、心肌梗塞和帕金森病的细胞替代疗法目前在治疗应用方面受到相当大的关注。从早期胚胎的内细胞团（ICM）收获的ES细胞可以在体外无限增殖，同时保留分化成所有体细胞的能力，从而提供无限的可再生体细胞来源。在这种情况下，鉴定可溶性因子，特别是化学合成的小分子，以及参与朝向限定的组织特异性细胞类型的特异性分化过程的信号级联对于优化用于治疗方法的体外体细胞的产生至关重要。然而，需要实验模型允许快速和“易于处理”的化学文库的平行筛选，以实现这一目标。最近，正向化学遗传筛选策略已被假定为筛选细胞系统中的小分子，以获得特定的所需表型效应。本文主要从化学遗传学的角度对ES细胞的研究进展进行综述，以寻找促进ES细胞特异性分化的小分子。基于细胞ES的细胞替代疗法背景下的化学遗传学在不久的将来仍然是包括化学、分子生物学、药物物理学和机器人技术在内的几个科学领域的挑战。
Cell replacement therapy of severe degenerative diseases such as diabetes, myocardial infarction and Parkinson's disease through transplantation of somatic cells generated from embryonic stem (ES) cells is currently receiving considerable attention for the therapeutic applications. ES cells harvested from the inner cell mass (ICM) of the early embryo, can proliferate indefinitely in vitro while retaining the ability to differentiate into all somatic cells thereby providing an unlimited renewable source of somatic cells. In this context, identifying soluble factors, in particular chemically synthesized small molecules, and signal cascades involved in specific differentiation processes toward a defined tissue specific cell type are crucial for optimizing the generation of somatic cells in vitro for therapeutic approaches. However, experimental models are required allowing rapid and "easy-to-handle" parallel screening of chemical libraries to achieve this goal. Recently, the forward chemical genetic screening strategy has been postulated to screen small molecules in cellular systems for a specific desired phenotypic effect. The current review is focused on the progress of ES cell research in the context of the chemical genetics to identify small molecules promoting specific differentiation of ES cells to desired cell phenotype. Chemical genetics in the context of the cell ES-based cell replacement therapy remains a challenge for the near future for several scientific fields including chemistry, molecular biology, medicinal physics and robotic technologies.