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PMID: 19570514 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6.

Cell stem cell ·Vol. 5 ·No. 1 ·2009-07-02 ·Pages 54-63

Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Semprun-Prieto L, Delafontaine P, Prockop DJ

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 x 10(6) 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. I.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.

MeSH Terms
Animals Cell Adhesion Molecules/metabolism Cell Migration Assays Gene Expression Profiling Heart/physiopathology Humans Inflammation Mediators/metabolism Infusions, Intravenous Lung/cytology,metabolism Mice Multipotent Stem Cells/metabolism,transplantation Myocardial Infarction/metabolism,pathology,therapy Pulmonary Embolism/metabolism Stromal Cells/metabolism
Chemicals
Cell Adhesion Molecules Inflammation Mediators Tnfaip6 protein, mouse
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lee Ryang Hwa
Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Pulin Andrey A
Seo Min Jeong
Kota Daniel J
Ylostalo Joni
Larson Benjamin L
Semprun-Prieto Laura
Delafontaine Patrice
Prockop Darwin J
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Article Info
Journal
Cell stem cell
Abbr.
Cell Stem Cell
ISSN
1875-9777
DOI
10.1016/j.stem.2009.05.003
Published
2009-07-02
Pages
54-63
Language
English
Region
United States
NLM ID
101311472
PMCID
PMC4154377
Subset
IM
Grants
NCRR NIH HHS · P40 RR017447-01 · United States
NCRR NIH HHS · P40 RR 17447 · United States
NHLBI NIH HHS · HL073252 · United States
NCRR NIH HHS · P40 RR017447 · United States
NHLBI NIH HHS · 1R01HL080682-01A2 · United States
NHLBI NIH HHS · P01 HL075161 · United States
NHLBI NIH HHS · R01 HL073252 · United States
NHLBI NIH HHS · R01 HL080682-04 · United States
NHLBI NIH HHS · P01 HL 075161 · United States
NHLBI NIH HHS · R01 HL080682 · United States
Databases
GEO
GSE15969
Corrections
CommentIn
PMID: 19570508
External Links
PubMed source DOI: 10.1016/j.stem.2009.05.003 PMC Full Text View journal details
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