TY - JOUR
T1 - Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction
AU - Malliaras, Konstantinos
AU - Ibrahim, Ahmed
AU - Tseliou, Eleni
AU - Liu, Weixin
AU - Sun, Baiming
AU - Middleton, Ryan C.
AU - Seinfeld, Jeffrey
AU - Wang, Lai
AU - Sharifi, Behrooz G.
AU - Marbán, Eduardo
PY - 2014
Y1 - 2014
N2 - Controversy surrounds the identity, origin, and physiologic role of endogenous cardiomyocyte progenitors in adult mammals. Using an inducible genetic labeling approach to identify small non-myocyte cells expressing cardiac markers, we find that activated endogenous cardioblasts are rarely evident in the normal adult mouse heart. However, myocardial infarction results in significant cardioblast activation at the site of injury. Genetically labeled isolated cardioblasts express cardiac transcription factors and sarcomeric proteins, exhibit spontaneous contractions, and form mature cardiomyocytes in vivo after injection into unlabeled recipient hearts. The activated cardioblasts do not arise from hematogenous seeding, cardiomyocyte dedifferentiation, or mere expansion of a preformed progenitor pool. Cell therapy with cardiosphere-derived cells amplifies innate cardioblast-mediated tissue regeneration, in part through the secretion of stromal cell-derived factor 1 by transplanted cells. Thus, stimulation of endogenous cardioblasts by exogenous cells mediates therapeutic regeneration of injured myocardium.
AB - Controversy surrounds the identity, origin, and physiologic role of endogenous cardiomyocyte progenitors in adult mammals. Using an inducible genetic labeling approach to identify small non-myocyte cells expressing cardiac markers, we find that activated endogenous cardioblasts are rarely evident in the normal adult mouse heart. However, myocardial infarction results in significant cardioblast activation at the site of injury. Genetically labeled isolated cardioblasts express cardiac transcription factors and sarcomeric proteins, exhibit spontaneous contractions, and form mature cardiomyocytes in vivo after injection into unlabeled recipient hearts. The activated cardioblasts do not arise from hematogenous seeding, cardiomyocyte dedifferentiation, or mere expansion of a preformed progenitor pool. Cell therapy with cardiosphere-derived cells amplifies innate cardioblast-mediated tissue regeneration, in part through the secretion of stromal cell-derived factor 1 by transplanted cells. Thus, stimulation of endogenous cardioblasts by exogenous cells mediates therapeutic regeneration of injured myocardium.
KW - Cardiac stem cells
KW - Cardioblasts
KW - Cardiomyocyte progenitor cells
KW - Cardiosphere-derived cells
KW - Heart regeneration
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U2 - 10.1002/emmm.201303626
DO - 10.1002/emmm.201303626
M3 - Article
C2 - 24797668
AN - SCOPUS:84901771653
SN - 1757-4676
VL - 6
SP - 760
EP - 777
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
IS - 6
ER -