Abstract
Homoeostasis of bone marrow microenvironment depends on a precise balance between cell proliferation and death, which is supported by the cellular-extracellular matrix crosstalk. Multipotent mesenchymal stromal cells (MSC) are the key elements to provide the specialized bone marrow microenvironment by supporting, maintaining, and regulating the functions and fate of haematopoietic stem cells. Despite the great potential of MSC for cell therapy in several diseases due to their regenerative, immunomodulatory, and anti-inflammatory properties, they can also contribute to modulate tumor microenvironment. The extracellular vesicles that comprise exosomes and microvesicles are important mediators of intercellular communication due to their ability to change phenotype and physiology of different cell types. These vesicles may interact not only with neighbouring cells but also with cells from distant tissues to either maintain tissue homoeostasis or participate in disease pathogenesis. This review focuses on the current knowledge about the physiological role of MSC-extracellular vesicles, as well as their deregulation in haematological malignancies and their potential applications as biomarkers for diagnosis, progression, and treatment monitoring of such diseases.
Highlights
Juçara Gastaldi Cominal,1,2 Maira da Costa Cacemiro,1 Belinda Pinto-Simões,2,3 Hans-Jochem Kolb,4 Kelen Cristina Ribeiro Malmegrim,2,5 and Fabíola Attié de Castro 2,5
This review focuses on the current knowledge about the physiological role of mesenchymal stromal cells (MSC)-extracellular vesicles, as well as their deregulation in haematological malignancies and their potential applications as biomarkers for diagnosis, progression, and treatment monitoring of such diseases
MSC-Extracellular vesicles (EV) contribute to disease pathogenesis by supporting the transformation of bone marrow (BM) microenvironment into a protumoral niche in haematological malignancies, enhancing angiogenesis, and promoting optimal conditions for tumor cell survival, proliferation, migration, and drug resistance
Summary
Multipotent mesenchymal stromal cells (MSC), known as mesenchymal stem cells or mesenchymal stromal cells, were described in the 1960s as a population of nonhaematopoietic cells of bone marrow (BM) microenvironment that support the haematopoiesis process [1, 2]. MSC produce many types of bioactive molecules: (i) adhesion molecules, such as vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and activated leucocyte cell adhesion molecule (ALCAM); (ii) growth factors, such as SCF, transforming growth factor beta (TGF-β), epidermal growth factor (EGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and hepatocyte growth factor (HGF); (iii) cytokines, such as the interleukins IL-1α, IL-1β, IL-6, IL-7, and IL-8; (iv) angiogenic factors, such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF); and (v) immunomodulatory molecules, such as prostaglandin E2 (PGE2), human leucocyte antigen G (HLA-G), and indoleamine 2,3-dioxygenase (IDO) [12,13,14,15]. Scientists and clinicians have considered MSC as a therapeutic agent and as a therapeutic target due to their participation in the modification of BM microenvironment and chemoresistance in malignant diseases
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