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Short-term memory of danger signals or environmental stimuli in mesenchymal stem cells: implications for therapeutic potential.

Abstract：

: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-α (TNF-α), 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-α stimulation. Collectively, our data suggest that MSCs have a short-term memory of environmental signals, which may impact their therapeutic potential.

journal_name

Cell Mol Immunol

journal_title

Cellular & molecular immunology

authors

Liu GY,Liu Y,Lu Y,Qin YR,Di GH,Lei YH,Liu HX,Li YQ,Wu C,Hu XW,Duan HF

doi

10.1038/cmi.2015.11

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

369-78

issue

3

eissn

1672-7681

issn

2042-0226

pii

cmi201511

journal_volume

13

pub_type

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