Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 13, Issue 3, Pages 369-378Publisher
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/cmi.2015.11
Keywords
environmental stimuli; mesenchymal stem cells; pre-conditioning; short-term memory
Categories
Funding
- Foundation of National Basic Research Program of China [2010CB529903, 2010CB833600, 2012CB518105]
- National Science Foundation of China [81201760, 81270894]
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Mesenchymal stem/stromal cells (MSCs) possess some characteristics of immune cells, including a pro-inflammatory phenotype, an immunosuppressive phenotype, antibacterial properties and the expression of Toll-like receptor proteins. Here we show that, similar to immune cells, MSCs retain information from danger signals or environmental stimuli for a period of time. When treated with the pro-inflammatory factors lipopolysaccharide (LPS) or tumor necrosis factor-a (TNF-alpha), MSCs display increased expression of IL-6, IL-8 and MCP-1. Following re-plating and several rounds of cell division in the absence of stimulating factors, the expression of IL-6, IL-8 and MCP-1 remained higher than in untreated cells for over 7 days. A spike in cytokine secretion occurred when cells were exposed to a second round of stimulation. We primed MSCs with LPS and LPS-primed MSCs had better therapeutic efficacy at promoting skin flap survival in a diabetic rat model than did unprimed MSCs. Finally, we found that several microRNAs, including miR146a, miR150 and miR155, along with the modification of DNA by 5-hydroxymethylcytosine (5hmC), mediate the MSC response to LPS and TNF-alpha stimulation. Collectively, our data suggest that MSCs have a short-term memory of environmental signals, which may impact their therapeutic potential.
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