Abstract
Pre-clinical and clinical studies revealed that mesenchymal stromal cell (MSC) transplants elicit tissue repair. Conditioning MSC prior to transplantation may boost their ability to support repair. We investigated macrophage-derived inflammation as a means to condition MSC by comprehensively analyzing their transcriptome and secretome. Conditioning MSC with macrophage-derived inflammation resulted in 3208 differentially expressed genes, which were annotated with significantly enriched GO terms for 1085 biological processes, 85 cellular components, and 79 molecular functions. Inflammation-mediated conditioning increased the secretion of growth factors that are key for tissue repair, including vascular endothelial growth factor, hepatocyte growth factor, nerve growth factor and glial-derived neurotrophic factor. Furthermore, we found that inflammation-mediated conditioning induces transcriptomic changes that challenge the viability and mobility of MSC. Our data support the notion that macrophage-derived inflammation stimulates MSC to augment their paracrine repair-supporting activity. The results suggest that inflammatory pre-conditioning enhances the therapeutic potential of MSC transplants.
Highlights
Cell transplantation is a therapeutic solution for damaged tissues with little regenerative capability and for inflammatory disorders [1,2,3,4,5,6]
We found that mesenchymal stromal cell (MSC) conditioned by macrophage-derived inflammation upregulate genes and increase the secretion of growth factors widely associated with promoting blood vessel formation, immunomodulation and tissue repair
We investigated the effect of conditioning MSCs with macrophage-derived inflammation by analyzing their transcriptome and secretome
Summary
Cell transplantation is a therapeutic solution for damaged tissues with little regenerative capability and for inflammatory disorders [1,2,3,4,5,6]. MSCs respond to signals in the damaged tissue environment and choreograph repair events with local cells [12,13,14]. The potential and advantages of MSCs for tissue repair prompted current clinical trials for the treatment of, among others, cardiac damage [4,15], spinal cord injury [2], musculoskeletal repair [16,17] and inflammatory disorders [18,19]. The search for means to augment the effects of MSC transplants on tissue repair is ongoing
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