Open AccessStimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction
Author(s) -
Malliaras Konstantinos,
Ibrahim Ahmed,
Tseliou Eleni,
Liu Weixin,
Sun Baiming,
Middleton Ryan C,
Seinfeld Jeffrey,
Wang Lai,
Sharifi Behrooz G,
Marbán Eduardo
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201303626
Subject(s) - endogeny , progenitor cell , stimulation , regeneration (biology) , myocyte , cell therapy , microbiology and biotechnology , stromal cell , myocardial infarction , biology , cell , stem cell , medicine , cancer research , endocrinology , genetics
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.