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Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6.

Authors :
Ryang Hwa Lee
Pulin, Andrey A.
Min Jeong Seo
Kota, Daniel J.
Ylostalo, Joni
Larson, Benjamin L.
Semprun-Prieto, Laura
Delafontaine, Patrice
Prockop, Darwin J.
Source :
Cell Stem Cell; Jul2009, Vol. 5 Issue 1, p54-63, 10p, 5 Graphs
Publication Year :
2009

Abstract

Quantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (i.v.) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 × 10<superscript>6</superscript> hMSCs were i.v. infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr, but <1000 cells appeared in six other tissues. The hMSCs in lung upregulated expression of multiple genes, with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, i.v. hMSCs, but not hMSCs transduced with TSG-6 siRNA, decreased inflammatory responses, reduced infarct size, and improved cardiac function. l.v. administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest that improvements in animal models and patients after i.v. infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19345909
Volume :
5
Issue :
1
Database :
Supplemental Index
Journal :
Cell Stem Cell
Publication Type :
Academic Journal
Accession number :
43515585
Full Text :
https://doi.org/10.1016/j.stem.2009.05.003