Human mesenchymal stromal cells from different tissues exhibit unique responses to different inflammatory stimuli

Abstract

BackgroundMesenchymal stromal cell (MSC) - based therapies are emerging as promising treatment of various autoimmune diseases, however the utility of different MSC tissue sources remains elusive. We aimed to characterize MSC from different origins, namely bone marrow (BM), adipose tissue (AT) and umbilical cord (UC) and determine their functional effects on normal human lung fibroblasts (NHLF). MethodsBM-, AT- or UC-MSC were isolated each from 3 different healthy donors. The gene expression and protein secretion were analyzed at basal level, along with TNFα-, IL-1β- and SAA- stimulated cells using real-time PCR and Luminex technology. Effect of conditioned medium (CM) from different MSC sources on migration was determined with wound scratch assay, while mitotic and apoptotic rates were studied using immunofluorescence microscopy. ResultsBM-MSC expressed highest basal mRNA levels of SDF1 and VCAM-1, while other genes were similarly expressed between MSC origins. TNFα priming of AT-MSC gained a prominent increase in IDO1 and CCL5 gene expression, with 928-fold and 4396-fold changes, respectively. Among all tissue sources, basal UC-MSC released highest protein levels of most measured analytes, including IL-6, IL-8, MCP-1, ICAM1, HGF, MMP1 and CH3L1. BM- and AT-MSC derived CM enhanced wound closure in NHLF, while an opposite effect was observed with UC-MSC derived CM. Our data also suggests that MSC-CM could contribute to decreased mitotic potential and increased apoptotic rate in lung fibroblasts. ConclusionsOur study highlights origin-specific MSC profile differences and emphasizes a heterogenic response of different MSC to inflammatory stimuli.