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.
Highlights
The bone marrow (BM) is a dynamic organ composed of hematopoietic stem cells (HSCs), their progeny, endothelial cells, and cells originating from mesenchymal stem cells (MSCs) such as osteoblasts and adipocytes
A series of clinical studies have examined the efficacy of systemic infusion of culture-expanded bone marrow stroma cells. cMET (BM-MSC) for acute Graft Versus Host Disease (GVHD) in allogeneic hematopoietic stem cell transplantation (HSCT)-treated patients and the results have shown overall responses ranging from 30% to 80% [82]
Beyond the potential roles in the physiology and pathophysiology of hematopoiesis, several studies have investigated the use of MSC-extracellular vesicles (EVs) as potential alternatives to MSCs for improving HSCs expansion and engraftment and for preventing GVHD following HSCT
Summary
The bone marrow (BM) is a dynamic organ composed of hematopoietic stem cells (HSCs), their progeny, endothelial cells, and cells originating from mesenchymal stem cells (MSCs) such as osteoblasts and adipocytes. In cases where immune responses are excessive, MSCs can suppress T cells, B cells, macrophages, dendritic cells, and natural killer (NK) cells [9,10] This immunomodulatory effect of MSCs is mainly mediated by producing different bioactive molecules such as adhesion molecules (intercellular adhesion molecule-1, ICAM-1, activated leukocyte cell adhesion molecule, ALCAM), growth factors (epidermal growth factor, EGF, transforming growth factor beta, TGF-β, granulocyte-macrophage colony-stimulating factor, GM-CSF), cytokines (inteleukin-IL-1α, IL1β, IL6, and IL8) angiogenic factors (Vascular Endothelial Growth Factor, VEGF; Platelet-Derived Growth Factor, PDGF) and immunomodulatory molecules (prostaglandin E2 (PGE2); human leukocyte antigen G (HLA-G) [11,12,13]. Similar to MSCs, MSC-EVs are involved in cell proliferation and differentiation, antigen presentation, angiogenesis, and demonstrate anti-inflammatory and regenerative properties [24,25]
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