TY - JOUR
T1 - Paracrine mechanisms in adult stem cell signaling and therapy
AU - Gnecchi, Massimiliano
AU - Zhang, Zhiping
AU - Ni, Aiguo
AU - Dzau, Victor J.
PY - 2008/11/21
Y1 - 2008/11/21
N2 - 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.
AB - 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.
KW - Adult stem cells
KW - Cytoprotection
KW - Neovascularization
KW - Paracrine signaling
KW - Regeneration
UR - http://www.scopus.com/inward/record.url?scp=58149347238&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.108.176826
DO - 10.1161/CIRCRESAHA.108.176826
M3 - Review article
C2 - 19028920
AN - SCOPUS:58149347238
SN - 0009-7330
VL - 103
SP - 1204
EP - 1219
JO - Circulation Research
JF - Circulation Research
IS - 11
ER -