Stem Cells Dev. 2018 Jul 10. doi: 10.1089/scd.2018.0091. [Epub ahead of print]

Manipulation of hematopoietic stem cell fate by small molecules compounds.

Zarrabi M^1,2, Afzal E³, Ebrahimi M⁴.

Abstract

Self-renewal and multi-potential differentiation are two important features of hematopoietic stem/progenitor cells (HS/PCs) which 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 hematopoietic stem cell research will be presented. We focus on the significant applications of SMCs related to HS/PC expansion and discuss the associated mechanism. In addition, we will give a short summary of the clinical approaches have used the SMCs.