Mitochondria Transfer in Bone Marrow Hematopoietic Activity

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. The alteration of mitochondrial dynamics, damaged mitochondrial clearance, and intercellular mitochondria transfer, fine-tuned by BM niche factors and stress signaling, has considerable impacts on hematopoietic and BM microenvironment regeneration. Elucidating the differential BM niche component on mitochondria transfer, the trigger signal, mode of transfer, and the fate of transferred mitochondria are essential to underpin their application in regenerative medicine and transplantation settings.