The Role of Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles (MSC-EVs) in Normal and Abnormal Hematopoiesis and Their Therapeutic Potential

Abstract

Mesenchymal stem cells (MSCs) represent a heterogeneous cellular population responsible for the support, maintenance, and regulation of normal hematopoietic stem cells (HSCs). In many hematological malignancies, however, MSCs are deregulated and may create an inhibitory microenvironment able to induce the disease initiation and/or progression. MSCs secrete soluble factors including extracellular vesicles (EVs), which may influence the bone marrow (BM) microenvironment via paracrine mechanisms. MSC-derived EVs (MSC-EVs) may even mimic the effects of MSCs from which they originate. Therefore, MSC-EVs contribute to the BM homeostasis but may also display multiple roles in the induction and maintenance of abnormal hematopoiesis. Compared to MSCs, MSC-EVs have been considered a more promising tool for therapeutic purposes including the prevention and treatment of Graft Versus Host Disease (GVHD) following allogenic HSC transplantation (HSCT). There are, however, still unanswered questions such as the molecular and cellular mechanisms associated with the supportive effect of MSC-EVs, the impact of the isolation, purification, large-scale production, storage conditions, MSC source, and donor characteristics on MSC-EV biological effects as well as the optimal dose and safety for clinical usage. This review summarizes the role of MSC-EVs in normal and malignant hematopoiesis and their potential contribution in treating GVHD.

Improving hematopoietic engraftment: Potential role of mesenchymal stromal cell-derived extracellular vesicles

“…EVs released by stromal cells in situ in the BM are known to contribute to the hematopoietic niche homeostasis, acting as signaling complex capable of modulate immune system function, BM microenvironment, angiogenesis or HSC development, among other functions. 25,26 MSC-EVs contain numerous bioactive molecules including growth factors, lipids, proteins, and nucleic acids that can be incorporated into HSCs and modulate their behavior, gene expression, and BM homing ability. 27,28 In a previous study, we have described to transfer its mRNA into human umbilical vein endothelial cells (HUVECs) that begin to express this fusion oncoprotein.…”

Mesenchymal Stem/Stromal Cells in Immunity and Disease: A Better Understanding for an Improved Use

“…Batsali, A.K. et al summarized the role and therapeutic potential of MSC-EVs (Extracellular vesicles) in normal and malignant hematopoiesis, as well as their potential contribution in treating Graft versus host disease (GVHD) [13]. Sava, R.I. et al reviewed how MSCs efficiently target immune dysregulation in Heart failure with preserved ejection fraction (HFpEF) and stop disease progression.…”

Exosome: From leukemia progression to a novel therapeutic approach in leukemia treatment

“…BMSC‐derived exosomes carry different cytokines and chemokines, which can increase migration, proliferation, and survival of MM cells by inhibiting the degradation of cleaved caspase‐9 and caspase‐3. These results indicate that despite differential composition of BMSCs and malignant cell exosomes, these cells can communicate with each other 117,118 . Additionally, the level of Gal‐3 mRNA and protein containing stromal cells‐derived exosome in B‐ALL have been reported to be associated with drug‐resistance through activated MEK/ERK pathway 104 .…”