Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis

Abstract

Background Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In intervertebral disc (IVD) cells, application of MSC secretome has been shown to decrease the apoptosis rate, induce proliferation, and promote production of extracellular matrix (ECM). For clinical translation of secretome-based treatment, characterization of the secretome composition is needed to better understand the induced biological processes and identify potentially effective secretomes. Methods This study aimed to investigate the proteome released by bone marrow-derived MSCs following exposure to a healthy, traumatic, or degenerative human IVD environment by mass spectroscopy and quantitative immunoassay analyses. Exposure of MSCs to the proinflammatory stimulus interleukin 1β (IL-1β) was used as control. Results Compared to MSC baseline secretome, there were 224 significantly up- or downregulated proteins following healthy, 179 following traumatic, 223 following degenerative IVD, and 160 proteins following IL-1β stimulus. Stimulation of MSCs with IVD conditioned media induced a more complex MSC secretome, involving more biological processes, compared to stimulation with IL-1β. The MSC response to stimulation with IVD conditioned medium was dependent on their pathological status. Conclusions The MSC secretome seemed to match the primary need of the IVD: homeostasis maintenance in the case of healthy IVDs, versus immunomodulation, adjustment of ECM synthesis and degradation disbalance, and ECM (re) organization in the case of traumatic and degenerative IVDs. These findings highlight the importance of cell preconditioning in the development of tailored secretome therapies. Graphical abstract The secretome of human bone marrow-derived mesenchymal stromal cells (MSCs) stimulated with intervertebral disc (IVD) conditioned medium was analyzed by proteomic profiling. Depending on the pathological state of the IVD, the MSC secretome protein composition indicated immunomodulatory or anabolic activity of the secretome. These findings may have implications for tailored secretome therapy for the IVD and other tissues.

Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine

“…In contrast, this does not happen when the cells are grown in the laboratory. Therefore, it might be necessary to customize the culture condition that mimics the pathophysiological environment to produce clinically effective secretome [162].…”

Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

“…Increasing evidence strongly suggests that cells respond to the needs of the microenvironment in which they are found. For instance, a recent study claimed that MSCs secretome seemed to address the primary need of the cell environment, presenting an immunomodulatory or anabolic MSC-derived secretome protein composition depending on the environmental pathological state [ 151 ]. Accordingly, it is not surprising that pre-conditioning of MSCs has shown to be effective in resisting recipient pathogenic microenvironmental impacts and improving regenerative potential [ 152 , 153 , 154 , 155 ].…”

Influence of Hypothermic Storage Fluids on Mesenchymal Stem Cell Stability: A Comprehensive Review and Personal Experience

“…MSCs secrete a variety of proangiogenic, chemotactic, anti-apoptotic, anti-inflammatory, immunomodulating and remodeling soluble factors—platelet-derived growth factor-B (PDGFB), vascular endothelial factor (VEGF), angiopoietin-1 (Ang1), chemokine (C-X-C) ligand (CXCL2, CXCL12), chemokine (C-C) ligand (CCL2, CCL5), interleukin-1 receptor antagonist (IL-1Ra), transforming growth factor beta (TGF-β), stromal-derived factor-1 (SDF1), indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), matrix metalloproteinase-9 (MMP-9), and others [ 16 , 18 , 19 ].…”