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PMID: 19028920 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Paracrine mechanisms in adult stem cell signaling and therapy.

Circulation research ·Vol. 103 ·No. 11 ·2008-11-21 ·Pages 1204-19

Gnecchi M, Zhang Z, Ni A, Dzau VJ

Abstract

Animal and preliminary human studies of adult cell therapy following acute myocardial infarction have shown an overall improvement of cardiac function. Myocardial and vascular regeneration have been initially proposed as mechanisms of stem cell action. However, in many cases, the frequency of stem cell engraftment and the number of newly generated cardiomyocytes and vascular cells, either by transdifferentiation or cell fusion, appear too low to explain the significant cardiac improvement described. Accordingly, we and others have advanced an alternative hypothesis: the transplanted stem cells release soluble factors that, acting in a paracrine fashion, contribute to cardiac repair and regeneration. Indeed, cytokines and growth factors can induce cytoprotection and neovascularization. It has also been postulated that paracrine factors may mediate endogenous regeneration via activation of resident cardiac stem cells. Furthermore, cardiac remodeling, contractility, and metabolism may also be influenced in a paracrine fashion. This article reviews the potential paracrine mechanisms involved in adult stem cell signaling and therapy.

MeSH Terms
Adult Stem Cells/physiology,transplantation Cell Death Cell Differentiation Cell Fusion Coronary Circulation/physiology Coronary Disease/therapy Humans Models, Biological Myocardial Contraction/physiology Myocardial Infarction/pathology,physiopathology,therapy Myocytes, Cardiac/cytology,physiology Neovascularization, Physiologic Signal Transduction
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gnecchi Massimiliano
Mandel Center for Hypertension Research, Duke University Medical Center, Durham, NC 27710, USA.
Zhang Zhiping
Ni Aiguo
Dzau Victor J
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Article Info
Journal
Circulation research
Abbr.
Circ Res
ISSN
1524-4571
DOI
10.1161/CIRCRESAHA.108.176826
Published
2008-11-21
Pages
1204-19
Language
English
Region
United States
NLM ID
0047103
PMCID
PMC2667788
Subset
IM
Grants
NHLBI NIH HHS · R01 HL081744-02 · United States
NHLBI NIH HHS · R01 HL035610 · United States
NHLBI NIH HHS · R01 HL035610-23 · United States
NHLBI NIH HHS · R01 HL35610 · United States
NHLBI NIH HHS · R01 HL73219 · United States
NHLBI NIH HHS · R01 HL073219-06A2 · United States
NHLBI NIH HHS · R01 HL072010-05 · United States
NHLBI NIH HHS · R01 HL72010 · United States
NHLBI NIH HHS · R01 HL073219 · United States
NHLBI NIH HHS · R01 HL081744 · United States
NHLBI NIH HHS · R01 HL81744 · United States
NHLBI NIH HHS · R01 HL072010 · United States
External Links
PubMed source DOI: 10.1161/CIRCRESAHA.108.176826 PMC Full Text View journal details
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