Cargando…

Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction

BACKGROUND: Induced pluripotent stem cells (iPSC) can be differentiated into cardiomyocytes and represent a possible autologous cell source for myocardial repair. We analyzed the engraftment and functional effects of murine iPSC-derived cardiomyocytes (iPSC-CMs) in a murine model of myocardial infar...

Descripción completa

Detalles Bibliográficos
Autores principales: Rojas, Sebastian V., Kensah, George, Rotaermel, Alexander, Baraki, Hassina, Kutschka, Ingo, Zweigerdt, Robert, Martin, Ulrich, Haverich, Axel, Gruh, Ina, Martens, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426598/
https://www.ncbi.nlm.nih.gov/pubmed/28493867
http://dx.doi.org/10.1371/journal.pone.0173222
_version_ 1783235505100423168
author Rojas, Sebastian V.
Kensah, George
Rotaermel, Alexander
Baraki, Hassina
Kutschka, Ingo
Zweigerdt, Robert
Martin, Ulrich
Haverich, Axel
Gruh, Ina
Martens, Andreas
author_facet Rojas, Sebastian V.
Kensah, George
Rotaermel, Alexander
Baraki, Hassina
Kutschka, Ingo
Zweigerdt, Robert
Martin, Ulrich
Haverich, Axel
Gruh, Ina
Martens, Andreas
author_sort Rojas, Sebastian V.
collection PubMed
description BACKGROUND: Induced pluripotent stem cells (iPSC) can be differentiated into cardiomyocytes and represent a possible autologous cell source for myocardial repair. We analyzed the engraftment and functional effects of murine iPSC-derived cardiomyocytes (iPSC-CMs) in a murine model of myocardial infarction. METHODS AND RESULTS: To maximize cardiomyocyte yield and purity a genetic purification protocol was applied. Murine iPSCs were genetically modified to express a Zeocin(™) resistance gene under control of the cardiac-specific α-myosin heavy chain (α-MHC, MYH6) promoter. Thus, CM selection was performed during in vitro differentiation. iPSC-CM aggregates (“cardiac bodies”, CBs) were transplanted on day 14 after LAD ligation into the hearts of previously LAD-ligated mice (800 CBs/animal; 2-3x10(6) CMs). Animals were treated with placebo (PBS, n = 14) or iPSC-CMs (n = 35). Myocardial remodeling and function were evaluated by magnetic resonance imaging (MRI), conductance catheter (CC) analysis and histological morphometry. In vitro and in vivo differentiation was investigated. Follow up was 28 days (including histological assessment and functional analysis). iPSC-CM purity was >99%. Transplanted iPSC-CMs formed mature grafts within the myocardium, expressed cardiac markers and exhibited sarcomeric structures. Intramyocardial transplantation of iPSC-CMs significantly improved myocardial remodeling and left ventricular function 28 days after LAD-ligation. CONCLUSIONS: We conclude that iPSCs can effectively be differentiated into cardiomyocytes and genetically enriched to high purity. iPSC derived cardiomyocytes engraft within the myocardium of LAD-ligated mice and contribute to improve left ventricular function.
format Online
Article
Text
id pubmed-5426598
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-54265982017-05-25 Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction Rojas, Sebastian V. Kensah, George Rotaermel, Alexander Baraki, Hassina Kutschka, Ingo Zweigerdt, Robert Martin, Ulrich Haverich, Axel Gruh, Ina Martens, Andreas PLoS One Research Article BACKGROUND: Induced pluripotent stem cells (iPSC) can be differentiated into cardiomyocytes and represent a possible autologous cell source for myocardial repair. We analyzed the engraftment and functional effects of murine iPSC-derived cardiomyocytes (iPSC-CMs) in a murine model of myocardial infarction. METHODS AND RESULTS: To maximize cardiomyocyte yield and purity a genetic purification protocol was applied. Murine iPSCs were genetically modified to express a Zeocin(™) resistance gene under control of the cardiac-specific α-myosin heavy chain (α-MHC, MYH6) promoter. Thus, CM selection was performed during in vitro differentiation. iPSC-CM aggregates (“cardiac bodies”, CBs) were transplanted on day 14 after LAD ligation into the hearts of previously LAD-ligated mice (800 CBs/animal; 2-3x10(6) CMs). Animals were treated with placebo (PBS, n = 14) or iPSC-CMs (n = 35). Myocardial remodeling and function were evaluated by magnetic resonance imaging (MRI), conductance catheter (CC) analysis and histological morphometry. In vitro and in vivo differentiation was investigated. Follow up was 28 days (including histological assessment and functional analysis). iPSC-CM purity was >99%. Transplanted iPSC-CMs formed mature grafts within the myocardium, expressed cardiac markers and exhibited sarcomeric structures. Intramyocardial transplantation of iPSC-CMs significantly improved myocardial remodeling and left ventricular function 28 days after LAD-ligation. CONCLUSIONS: We conclude that iPSCs can effectively be differentiated into cardiomyocytes and genetically enriched to high purity. iPSC derived cardiomyocytes engraft within the myocardium of LAD-ligated mice and contribute to improve left ventricular function. Public Library of Science 2017-05-11 /pmc/articles/PMC5426598/ /pubmed/28493867 http://dx.doi.org/10.1371/journal.pone.0173222 Text en © 2017 Rojas et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rojas, Sebastian V.
Kensah, George
Rotaermel, Alexander
Baraki, Hassina
Kutschka, Ingo
Zweigerdt, Robert
Martin, Ulrich
Haverich, Axel
Gruh, Ina
Martens, Andreas
Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction
title Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction
title_full Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction
title_fullStr Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction
title_full_unstemmed Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction
title_short Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction
title_sort transplantation of purified ipsc-derived cardiomyocytes in myocardial infarction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426598/
https://www.ncbi.nlm.nih.gov/pubmed/28493867
http://dx.doi.org/10.1371/journal.pone.0173222
work_keys_str_mv AT rojassebastianv transplantationofpurifiedipscderivedcardiomyocytesinmyocardialinfarction
AT kensahgeorge transplantationofpurifiedipscderivedcardiomyocytesinmyocardialinfarction
AT rotaermelalexander transplantationofpurifiedipscderivedcardiomyocytesinmyocardialinfarction
AT barakihassina transplantationofpurifiedipscderivedcardiomyocytesinmyocardialinfarction
AT kutschkaingo transplantationofpurifiedipscderivedcardiomyocytesinmyocardialinfarction
AT zweigerdtrobert transplantationofpurifiedipscderivedcardiomyocytesinmyocardialinfarction
AT martinulrich transplantationofpurifiedipscderivedcardiomyocytesinmyocardialinfarction
AT haverichaxel transplantationofpurifiedipscderivedcardiomyocytesinmyocardialinfarction
AT gruhina transplantationofpurifiedipscderivedcardiomyocytesinmyocardialinfarction
AT martensandreas transplantationofpurifiedipscderivedcardiomyocytesinmyocardialinfarction