Abstract
Mesenchymal stem cell (MSC)-sourced secretome, defined as the set of MSC-derived bioactive factors (soluble proteins, nucleic acids, lipids and extracellular vesicles), showed therapeutic effects similar to those observed after transplantation of MSCs. MSC-derived secretome may bypass many side effects of MSC-based therapy, including unwanted differentiation of engrafted MSCs. In contrast to MSCs which had to be expanded in culture to reach optimal cell number for transplantation, MSC-sourced secretome is immediately available for treatment of acute conditions, including fulminant hepatitis, cerebral ischemia and myocardial infarction. Additionally, MSC-derived secretome could be massively produced from commercially available cell lines avoiding invasive cell collection procedure. In this review article we emphasized molecular and cellular mechanisms that were responsible for beneficial effects of MSC-derived secretomes in the treatment of degenerative and inflammatory diseases of hepatobiliary, respiratory, musculoskeletal, gastrointestinal, cardiovascular and nervous system. Results obtained in a large number of studies suggested that administration of MSC-derived secretomes represents a new, cell-free therapeutic approach for attenuation of inflammatory and degenerative diseases. Therapeutic effects of MSC-sourced secretomes relied on their capacity to deliver genetic material, growth and immunomodulatory factors to the target cells enabling activation of anti-apoptotic and pro-survival pathways that resulted in tissue repair and regeneration.
Highlights
Many degenerative and inflammatory diseases are in the focus of stem cell-based research
In contrast to Mesenchymal stem cell (MSC) which had to be expanded in culture to reach optimal cell number for transplantation, MSC-sourced secretome is immediately available for treatment of acute conditions including fulminant hepatitis, cerebral ischemia and myocardial infarction [39]
Contains low levels of factors which promote tumor growth (epidermal growth factor receptor (EGFR), fibroblast growth factor (FGF)-4 and -9), neo-angiogenesis (VEGF, IL-6, IL6 receptor), homing of naïve T cells to peripheral lymph nodes (chemokine (C-C motif) ligand 7 (CCL7)) and migration of circulating monocytes in tumor tissue (macrophage migration inhibitory factor (MMIF)) [37]. These findings indicate that MSC-derived conditioned medium (MSC-conditioned medium (CM))-based effects depend on MSCs origin and suggest that content of MSC-CM should be precisely determined before clinical application
Summary
Many degenerative and inflammatory diseases are in the focus of stem cell-based research. In this review article we summarized findings obtained in preclinical and clinical studies that delineated molecular and cellular mechanisms which were responsible for beneficial effects of MSC-derived secretomes in attenuation of degenerative and inflammatory diseases of hepatobiliary, respiratory, musculoskeletal, gastrointestinal, cardiovascular and nervous system. Various biological effects were observed in experimental animals after administration of MSC-CM and MSC-EVs. Importantly, MSC-sourced secretome bypassed many limitations of MSC-based therapy, including unwanted differentiation and potential activation of allogeneic immune response. MSC-sourced secretomes showed immunoregulatory, angiomodulatory and anti-apoptotic effects that resulted in enhanced tissue repair and regeneration [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41]
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