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...
Main Authors: | , , , , , , , , , |
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Format: | Article |
Language: | English |
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Springer Nature
2014-06-01
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Series: | EMBO Molecular Medicine |
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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. |
first_indexed | 2024-03-07T16:31:47Z |
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id | doaj.art-a219c1f4020b4be6ab0b044197eaa387 |
institution | Directory Open Access Journal |
issn | 1757-4676 1757-4684 |
language | English |
last_indexed | 2024-03-07T16:31:47Z |
publishDate | 2014-06-01 |
publisher | Springer Nature |
record_format | Article |
series | EMBO Molecular Medicine |
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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