Extracellular vesicles in the hematopoietic microenvironment

Abstract

Self-renewal and differentiation are defining characteristics of hematopoietic stem and progenitor cells, and their balanced regulation is central to lifelong function of both blood and immune systems. In addition to cell-intrinsic programs, hematopoietic stem and progenitor cell fate decisions are subject to extrinsic cues from within the bone marrow microenvironment and systemically. Yet, many of the paracrine and endocrine mediators that shape hematopoietic function remain to be discovered. Extracellular vesicles serve as evolutionarily conserved, constitutive regulators of cell and tissue homeostasis, with several recent reports supporting a role for extracellular vesicles in the regulation of hematopoiesis. We review the physiological and pathophysiological effects that extracellular vesicles have on bone marrow compartmental function while highlighting progress in understanding vesicle biogenesis, cargo incorporation, differential uptake, and downstream effects of vesicle internalization. This review also touches on the role of extracellular vesicles in hematopoietic stem and progenitor cell fate regulation and recent advances in therapeutic and diagnostic applications of extracellular vesicles in hematologic disorders.

Extracellular vesicles impose quiescence on residual hematopoietic stem cells in the leukemic niche

“…EV trafficking serves a broad range of constitutive cellular functions, whereby several subclasses of nano-sized vesicles transfer protein and nucleic acids between cells, including the BM niche [18,26,28,29,48,54]. We previously reported the loss of BM progenitors as a result of AML-EV trafficking [17].…”

“…Unlike the depletion of highly susceptible HSPC, HSC have proved to be more resilient during leukemic invasion, and multiple groups reported the relative accumulation of primitive hematopoietic cells in both murine models and xenograft studies [8,15,16,[21][22][23]. Extracellular vesicles (EV) comprise multiple populations of nano-sized vesicles, which carry protein and nucleic acids, participate in the regulation of BM function [24][25][26]. Extracellular vesicles (EV) comprise multiple populations of nano-sized vesicles, which carry protein and nucleic acids, participate in the regulation of BM function [24][25][26].…”

Circulating megakaryocyte and platelet microvesicles correlate with response to ruxolitinib and distinct disease severity in patients with myelofibrosis

“…Extracellular microvesicles (MVs) are size‐heterogeneous small vesicles (100–1000 nm) with pleiotropic effects on cell signalling, including immunity and inflammation (Butler et al , ). Megakaryocyte‐ and platelet‐MVs are the most abundant in peripheral blood (PB).…”

Evaluation of bone marrow microenvironment could change how myelodysplastic syndromes are diagnosed and treated

“…MSC-derived EVs promote the myeloid-biased expansion of HSPCs through theTLR-4 pathway, and megakaryocyte-derived microvesicles (MVs) increase differentiation of new megakaryocytes through RNA-mediated signaling (66). MSC-derived EVs promote the myeloid-biased expansion of HSPCs through theTLR-4 pathway, and megakaryocyte-derived microvesicles (MVs) increase differentiation of new megakaryocytes through RNA-mediated signaling (66).…”