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Immature human engineered heart tissues engraft in a guinea pig chronic injury model
Engineered heart tissue (EHT) transplantation represents an innovative, regenerative approach for heart failure patients. Late preclinical trials are underway, and a first clinical trial started recently. Preceding studies revealed functional recovery after implantation of in vitro-matured EHT in th...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259837/ https://www.ncbi.nlm.nih.gov/pubmed/37272385 http://dx.doi.org/10.1242/dmm.049834 |
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author | von Bibra, Constantin Shibamiya, Aya Bähr, Andrea Geertz, Birgit Köhne, Maria Stuedemann, Tim Starbatty, Jutta Horneffer-van der Sluis, Verena Klostermeier, Ulrich C. Hornaschewitz, Nadja Li, Xinghai Wolf, Eckhard Klymiuk, Nikolai Krane, Markus Kupatt, Christian Hiebl, Bernhard Eschenhagen, Thomas Weinberger, Florian |
author_facet | von Bibra, Constantin Shibamiya, Aya Bähr, Andrea Geertz, Birgit Köhne, Maria Stuedemann, Tim Starbatty, Jutta Horneffer-van der Sluis, Verena Klostermeier, Ulrich C. Hornaschewitz, Nadja Li, Xinghai Wolf, Eckhard Klymiuk, Nikolai Krane, Markus Kupatt, Christian Hiebl, Bernhard Eschenhagen, Thomas Weinberger, Florian |
author_sort | von Bibra, Constantin |
collection | PubMed |
description | Engineered heart tissue (EHT) transplantation represents an innovative, regenerative approach for heart failure patients. Late preclinical trials are underway, and a first clinical trial started recently. Preceding studies revealed functional recovery after implantation of in vitro-matured EHT in the subacute stage, whereas transplantation in a chronic injury setting was less efficient. When transplanting matured EHTs, we noticed that cardiomyocytes undergo a dedifferentiation step before eventually forming structured grafts. Therefore, we wanted to evaluate whether immature EHT (EHT(Im)) patches can be used for transplantation. Chronic myocardial injury was induced in a guinea pig model. EHT(Im) (15×10(6) cells) were transplanted within hours after casting. Cryo-injury led to large transmural scars amounting to 26% of the left ventricle. Grafts remuscularized 9% of the scar area on average. Echocardiographic analysis showed some evidence of improvement of left-ventricular function after EHT(Im) transplantation. In a small translational proof-of-concept study, human scale EHT(Im) patches (4.5×10(8) cells) were epicardially implanted on healthy pig hearts (n=2). In summary, we provide evidence that transplantation of EHT(Im) patches, i.e. without precultivation, is feasible, with similar engraftment results to those obtained using matured EHT. |
format | Online Article Text |
id | pubmed-10259837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-102598372023-06-13 Immature human engineered heart tissues engraft in a guinea pig chronic injury model von Bibra, Constantin Shibamiya, Aya Bähr, Andrea Geertz, Birgit Köhne, Maria Stuedemann, Tim Starbatty, Jutta Horneffer-van der Sluis, Verena Klostermeier, Ulrich C. Hornaschewitz, Nadja Li, Xinghai Wolf, Eckhard Klymiuk, Nikolai Krane, Markus Kupatt, Christian Hiebl, Bernhard Eschenhagen, Thomas Weinberger, Florian Dis Model Mech Research Article Engineered heart tissue (EHT) transplantation represents an innovative, regenerative approach for heart failure patients. Late preclinical trials are underway, and a first clinical trial started recently. Preceding studies revealed functional recovery after implantation of in vitro-matured EHT in the subacute stage, whereas transplantation in a chronic injury setting was less efficient. When transplanting matured EHTs, we noticed that cardiomyocytes undergo a dedifferentiation step before eventually forming structured grafts. Therefore, we wanted to evaluate whether immature EHT (EHT(Im)) patches can be used for transplantation. Chronic myocardial injury was induced in a guinea pig model. EHT(Im) (15×10(6) cells) were transplanted within hours after casting. Cryo-injury led to large transmural scars amounting to 26% of the left ventricle. Grafts remuscularized 9% of the scar area on average. Echocardiographic analysis showed some evidence of improvement of left-ventricular function after EHT(Im) transplantation. In a small translational proof-of-concept study, human scale EHT(Im) patches (4.5×10(8) cells) were epicardially implanted on healthy pig hearts (n=2). In summary, we provide evidence that transplantation of EHT(Im) patches, i.e. without precultivation, is feasible, with similar engraftment results to those obtained using matured EHT. The Company of Biologists Ltd 2023-06-05 /pmc/articles/PMC10259837/ /pubmed/37272385 http://dx.doi.org/10.1242/dmm.049834 Text en © 2023. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article von Bibra, Constantin Shibamiya, Aya Bähr, Andrea Geertz, Birgit Köhne, Maria Stuedemann, Tim Starbatty, Jutta Horneffer-van der Sluis, Verena Klostermeier, Ulrich C. Hornaschewitz, Nadja Li, Xinghai Wolf, Eckhard Klymiuk, Nikolai Krane, Markus Kupatt, Christian Hiebl, Bernhard Eschenhagen, Thomas Weinberger, Florian Immature human engineered heart tissues engraft in a guinea pig chronic injury model |
title | Immature human engineered heart tissues engraft in a guinea pig chronic injury model |
title_full | Immature human engineered heart tissues engraft in a guinea pig chronic injury model |
title_fullStr | Immature human engineered heart tissues engraft in a guinea pig chronic injury model |
title_full_unstemmed | Immature human engineered heart tissues engraft in a guinea pig chronic injury model |
title_short | Immature human engineered heart tissues engraft in a guinea pig chronic injury model |
title_sort | immature human engineered heart tissues engraft in a guinea pig chronic injury model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259837/ https://www.ncbi.nlm.nih.gov/pubmed/37272385 http://dx.doi.org/10.1242/dmm.049834 |
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