Center of Bioinformatics, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, PR China.
Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan; Department of Bioinformatics and Biotechnology, Government College University of Faisalabad, 38000, Pakistan.
Comput Biol Med. 2024 Jul;177:108661. doi: 10.1016/j.compbiomed.2024.108661. Epub 2024 May 27.
With the use of specific genetic factors and recent developments in cellular reprogramming, it is now possible to generate lineage-committed cells or induced pluripotent stem cells (iPSCs) from readily available and common somatic cell types. However, there are still significant doubts regarding the safety and effectiveness of the current genetic methods for reprogramming cells, as well as the conventional culture methods for maintaining stem cells. Small molecules that target specific epigenetic processes, signaling pathways, and other cellular processes can be used as a complementary approach to manipulate cell fate to achieve a desired objective. It has been discovered that a growing number of small molecules can support lineage differentiation, maintain stem cell self-renewal potential, and facilitate reprogramming by either increasing the efficiency of reprogramming or acting as a genetic reprogramming factor substitute. However, ongoing challenges include improving reprogramming efficiency, ensuring the safety of small molecules, and addressing issues with incomplete epigenetic resetting. Small molecule iPSCs have significant clinical applications in regenerative medicine and personalized therapies. This review emphasizes the versatility and potential safety benefits of small molecules in overcoming challenges associated with the iPSCs reprogramming process.
利用特定的遗传因素和最近的细胞重编程进展，现在可以从易于获得的常见体细胞类型中生成谱系定向细胞或诱导多能干细胞（iPSC）。然而，对于当前用于重编程细胞的遗传方法以及维持干细胞的常规培养方法的安全性和有效性仍然存在重大疑问。针对特定表观遗传过程、信号通路和其他细胞过程的小分子可以作为一种补充方法来操纵细胞命运，以实现预期的目标。已经发现，越来越多的小分子可以支持谱系分化、维持干细胞自我更新潜力，并通过提高重编程效率或作为遗传重编程因子替代物来促进重编程。然而，持续存在的挑战包括提高重编程效率、确保小分子的安全性以及解决不完全的表观遗传重置问题。小分子 iPSC 在再生医学和个性化治疗中有重要的临床应用。本综述强调了小分子在克服与 iPSC 重编程过程相关的挑战方面的多功能性和潜在的安全益处。
