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 e...

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Main Authors: Konstantinos Malliaras, Ahmed Ibrahim, Eleni Tseliou, Weixin Liu, Baiming Sun, Ryan C Middleton, Jeffrey Seinfeld, Lai Wang, Behrooz G Sharifi, Eduardo Marbán
Format: Article
Language:English
Published: Springer Nature 2014-06-01
Series:EMBO Molecular Medicine
Subjects:
Online Access:https://doi.org/10.1002/emmm.201303626
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author Konstantinos Malliaras
Ahmed Ibrahim
Eleni Tseliou
Weixin Liu
Baiming Sun
Ryan C Middleton
Jeffrey Seinfeld
Lai Wang
Behrooz G Sharifi
Eduardo Marbán
author_facet Konstantinos Malliaras
Ahmed Ibrahim
Eleni Tseliou
Weixin Liu
Baiming Sun
Ryan C Middleton
Jeffrey Seinfeld
Lai Wang
Behrooz G Sharifi
Eduardo Marbán
author_sort Konstantinos Malliaras
collection DOAJ
description 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.
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spelling doaj.art-a219c1f4020b4be6ab0b044197eaa3872024-03-03T10:20:06ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842014-06-016676077710.1002/emmm.201303626Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarctionKonstantinos Malliaras0Ahmed Ibrahim1Eleni Tseliou2Weixin Liu3Baiming Sun4Ryan C Middleton5Jeffrey Seinfeld6Lai Wang7Behrooz G Sharifi8Eduardo Marbán9Cedars‐Sinai Heart Institute Los Angeles CA USACedars‐Sinai Heart Institute Los Angeles CA USACedars‐Sinai Heart Institute Los Angeles CA USACedars‐Sinai Heart Institute Los Angeles CA USACedars‐Sinai Heart Institute Los Angeles CA USACedars‐Sinai Heart Institute Los Angeles CA USACedars‐Sinai Heart Institute Los Angeles CA USACedars‐Sinai Heart Institute Los Angeles CA USACedars‐Sinai Heart Institute Los Angeles CA USACedars‐Sinai Heart Institute Los Angeles CA USAAbstract 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.https://doi.org/10.1002/emmm.201303626cardiac stem cellscardioblastscardiomyocyte progenitor cellscardiosphere‐derived cellsheart regeneration
spellingShingle Konstantinos Malliaras
Ahmed Ibrahim
Eleni Tseliou
Weixin Liu
Baiming Sun
Ryan C Middleton
Jeffrey Seinfeld
Lai Wang
Behrooz G Sharifi
Eduardo Marbán
Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction
EMBO Molecular Medicine
cardiac stem cells
cardioblasts
cardiomyocyte progenitor cells
cardiosphere‐derived cells
heart regeneration
title Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction
title_full Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction
title_fullStr Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction
title_full_unstemmed Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction
title_short Stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction
title_sort stimulation of endogenous cardioblasts by exogenous cell therapy after myocardial infarction
topic cardiac stem cells
cardioblasts
cardiomyocyte progenitor cells
cardiosphere‐derived cells
heart regeneration
url https://doi.org/10.1002/emmm.201303626
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