1 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology , ACECR, Tehran, Iran .
2 Royan Stem Cell Technology Company , Cord Blood Bank, Tehran, Iran .
Stem Cells Dev. 2018 Sep 1;27(17):1175-1190. doi: 10.1089/scd.2018.0091. Epub 2018 Aug 22.
Self-renewal and multipotential differentiation are two important features of hematopoietic stem/progenitor cells (HS/PCs) that make them as an ideal source of stem cells for treatment of many hematologic disorders and cancers. Regarding the limited number of cord blood HS/PCs, proper ex vivo expansion can significantly increase the clinical use of cord blood stem cells. Meanwhile, expansion of HS/PCs will be feasible through bypassing the quiescent state of HS/PCs and simultaneously enhancing their proliferative potential and survival while delaying the terminal differentiation and exhaustion. Previous investigations have demonstrated that defined sets of exogenous hematopoietic cytokines/growth factors such as stem cell factor, Flt-3 ligand, and thrombopoietin are able to expand HS/PCs. However, in recent years, small molecule compounds (SMCs) have emerged as a powerful tool for the effective expansion of HS/PCs by modulating multiple cellular processes including different signaling pathways and epigenetics. In this review, recent progress toward the use of SMCs in HS cell research is presented. We focus on the significant applications of SMCs related to HS/PC expansion and discuss the associated mechanism. At the end we present a list of those SMCs which enter to clinical trials.
自我更新和多能分化是造血干/祖细胞 (HS/PCs) 的两个重要特征，使它们成为治疗许多血液疾病和癌症的理想干细胞来源。鉴于脐带血 HS/PCs 的数量有限，适当的体外扩增可以显著增加脐带血干细胞的临床应用。同时，通过绕过 HS/PCs 的静止状态，同时增强其增殖潜力和生存能力，同时延迟终末分化和衰竭，扩增 HS/PCs 将成为可行的。先前的研究表明，定义的外源性造血细胞因子/生长因子（如干细胞因子、Flt-3 配体和血小板生成素）能够扩增 HS/PCs。然而，近年来，小分子化合物 (SMCs) 通过调节包括不同信号通路和表观遗传学在内的多种细胞过程，已成为有效扩增 HS/PCs 的有力工具。在本文中，我们介绍了 SMCs 在 HS 细胞研究中的最新进展。我们重点介绍了 SMCs 在 HS/PC 扩增方面的重要应用，并讨论了相关的机制。最后，我们列出了那些进入临床试验的 SMCs。
