Singh Abhishek K, Cancelas Jose A
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
Hoxworth Blood Center, University of Cincinnati Academic Health Center, Cincinnati, OH, USA.
Curr Stem Cell Rep. 2021 Mar;7(1):1-12. doi: 10.1007/s40778-020-00185-z. Epub 2021 Jan 14.
The well-established crosstalk between hematopoietic stem cells (HSC) and bone marrow (BM) microenvironment is critical for the homeostasis and hematopoietic regeneration in response to blood formation emergencies. Past decade has witnessed that the intercellular communication mediated by the transfer of cytoplasmic material and organelles between cells can regenerate and/or repair the damaged cells. Mitochondria have recently emerged as a potential regulator of HSC fate. This review intends to discuss recent advances in the understanding of the mitochondrial dynamics, specifically focused on the role of mitochondrial transfer, in the maintenance of HSC activity with clear implications in stem cell transplantation and regenerative medicine.
HSC are highly heterogeneous in their mitochondrial metabolism, and the quiescence and potency of HSC depend on the status of mitochondrial dynamics and the clearance of damaged mitochondria. Recent evidence has shown that in stress response, BM stromal cells transfer healthy mitochondria to HSC, facilitate HSC bioenergetics shift towards oxidative phosphorylation, and subsequently stimulate leukocyte expansion. Furthermore, metabolic rewiring following mitochondria transfer from HSPC to BM stromal cells likely to repair the damaged BM niche and accelerate limiting HSC transplantation post myeloablative conditioning.
造血干细胞(HSC)与骨髓(BM)微环境之间已确立的相互作用对于应对造血紧急情况时的体内平衡和造血再生至关重要。过去十年见证了细胞间通过细胞质物质和细胞器转移介导的细胞间通讯能够再生和/或修复受损细胞。线粒体最近已成为HSC命运的潜在调节因子。本综述旨在讨论线粒体动力学理解方面的最新进展,特别关注线粒体转移在维持HSC活性中的作用,这对干细胞移植和再生医学具有明确意义。
HSC在其线粒体代谢方面高度异质,HSC的静止和潜能取决于线粒体动力学状态和受损线粒体的清除。最近的证据表明,在应激反应中,BM基质细胞将健康线粒体转移至HSC,促进HSC生物能量学向氧化磷酸化转变,并随后刺激白细胞扩增。此外,HSPC向BM基质细胞转移线粒体后的代谢重编程可能修复受损的BM微环境,并加速清髓性预处理后的有限HSC移植。