Macrophage-Derived Inflammation Induces a Transcriptome Makeover in Mesenchymal Stromal Cells Enhancing Their Potential for Tissue Repair

International Journal of Molecular Sciences

Joost Verhaagen¹  Oliver Umland²  Martin Oudega³  Nick O’Neill⁴  Inés Maldonado-Lasunción⁴ 

[1] Department of Regeneration of Sensorimotor Systems, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105 BA, The Netherlands;Diabetes Research Institute, University of Miami, Miami, FL 33136, USA;Shirley Ryan AbilityLab, Chicago, IL 60611, USA;The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA;

关键词: monocytes;    immune response;    mesenchymal stem cells;    growth factors;    immunomodulation;    regeneration;   

DOI  :  10.3390/ijms22020781

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown