title: Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction.
abstract: 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.
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Malliaras
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ibrahim
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
authors.forename: Eleni
authors.initials: E
authors.lastname: Tseliou
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
authors.forename: Weixin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
authors.forename: Baiming
authors.initials: B
authors.lastname: Sun
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Middleton
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Seinfeld
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
authors.forename: Lai
authors.initials: L
authors.lastname: Wang
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
authors.forename: Behrooz G
authors.initials: BG
authors.lastname: Sharifi
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA Eduardo.Marban@csmc.edu.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D005260:Female; D006321:Heart / Q000502:physiology*; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse
keywords: cardiac stem cells; cardioblasts; cardiomyocyte progenitor cells; cardiosphere‐derived cells; heart regeneration