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Immature human engineered heart tissues engraft in a guinea pig chronic injury model

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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.

In: DIS MODEL MECH, Vol. 16, No. 5, dmm049834, 01.05.2023.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

von Bibra, C, Shibamiya, A, Bähr, A, Geertz, B, Köhne, M, Stuedemann, T, Starbatty, J, Horneffer-van der Sluis, V, Klostermeier, UC, Hornaschewitz, N, Li, X, Wolf, E, Klymiuk, N, Krane, M, Kupatt, C, Hiebl, B, Eschenhagen, T & Weinberger, F 2023, 'Immature human engineered heart tissues engraft in a guinea pig chronic injury model', DIS MODEL MECH, vol. 16, no. 5, dmm049834. https://doi.org/10.1242/dmm.049834

APA

von Bibra, C., Shibamiya, A., Bähr, A., Geertz, B., Köhne, M., Stuedemann, T., Starbatty, J., Horneffer-van der Sluis, V., Klostermeier, U. C., Hornaschewitz, N., Li, X., Wolf, E., Klymiuk, N., Krane, M., Kupatt, C., Hiebl, B., Eschenhagen, T., & Weinberger, F. (2023). Immature human engineered heart tissues engraft in a guinea pig chronic injury model. DIS MODEL MECH, 16(5), [dmm049834]. https://doi.org/10.1242/dmm.049834

Vancouver

von Bibra C, Shibamiya A, Bähr A, Geertz B, Köhne M, Stuedemann T et al. Immature human engineered heart tissues engraft in a guinea pig chronic injury model. DIS MODEL MECH. 2023 May 1;16(5). dmm049834. https://doi.org/10.1242/dmm.049834

Bibtex

@article{f04f2000e084484898c89b48cf714051,
title = "Immature human engineered heart tissues engraft in a guinea pig chronic injury model",
abstract = "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 (EHTIm) patches can be used for transplantation. Chronic myocardial injury was induced in a guinea pig model. EHTIm (15×106 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 EHTIm transplantation. In a small translational proof-of-concept study, human scale EHTIm patches (4.5×108 cells) were epicardially implanted on healthy pig hearts (n=2). In summary, we provide evidence that transplantation of EHTIm patches, i.e. without precultivation, is feasible, with similar engraftment results to those obtained using matured EHT.",
keywords = "Humans, Guinea Pigs, Animals, Heart, Myocytes, Cardiac, Heart Ventricles, Echocardiography, Tissue Engineering/methods, Cell Differentiation, Myocardium",
author = "{von Bibra}, Constantin and Aya Shibamiya and Andrea B{\"a}hr and Birgit Geertz and Maria K{\"o}hne and Tim Stuedemann and Jutta Starbatty and {Horneffer-van der Sluis}, Verena and Klostermeier, {Ulrich C} and Nadja Hornaschewitz and Xinghai Li and Eckhard Wolf and Nikolai Klymiuk and Markus Krane and Christian Kupatt and Bernhard Hiebl and Thomas Eschenhagen and Florian Weinberger",
note = "{\textcopyright} 2023. Published by The Company of Biologists Ltd.",
year = "2023",
month = may,
day = "1",
doi = "10.1242/dmm.049834",
language = "English",
volume = "16",
journal = "DIS MODEL MECH",
issn = "1754-8403",
publisher = "Company of Biologists Ltd",
number = "5",

}

RIS

TY - JOUR

T1 - Immature human engineered heart tissues engraft in a guinea pig chronic injury model

AU - von Bibra, Constantin

AU - Shibamiya, Aya

AU - Bähr, Andrea

AU - Geertz, Birgit

AU - Köhne, Maria

AU - Stuedemann, Tim

AU - Starbatty, Jutta

AU - Horneffer-van der Sluis, Verena

AU - Klostermeier, Ulrich C

AU - Hornaschewitz, Nadja

AU - Li, Xinghai

AU - Wolf, Eckhard

AU - Klymiuk, Nikolai

AU - Krane, Markus

AU - Kupatt, Christian

AU - Hiebl, Bernhard

AU - Eschenhagen, Thomas

AU - Weinberger, Florian

N1 - © 2023. Published by The Company of Biologists Ltd.

PY - 2023/5/1

Y1 - 2023/5/1

N2 - 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 (EHTIm) patches can be used for transplantation. Chronic myocardial injury was induced in a guinea pig model. EHTIm (15×106 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 EHTIm transplantation. In a small translational proof-of-concept study, human scale EHTIm patches (4.5×108 cells) were epicardially implanted on healthy pig hearts (n=2). In summary, we provide evidence that transplantation of EHTIm patches, i.e. without precultivation, is feasible, with similar engraftment results to those obtained using matured EHT.

AB - 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 (EHTIm) patches can be used for transplantation. Chronic myocardial injury was induced in a guinea pig model. EHTIm (15×106 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 EHTIm transplantation. In a small translational proof-of-concept study, human scale EHTIm patches (4.5×108 cells) were epicardially implanted on healthy pig hearts (n=2). In summary, we provide evidence that transplantation of EHTIm patches, i.e. without precultivation, is feasible, with similar engraftment results to those obtained using matured EHT.

KW - Humans

KW - Guinea Pigs

KW - Animals

KW - Heart

KW - Myocytes, Cardiac

KW - Heart Ventricles

KW - Echocardiography

KW - Tissue Engineering/methods

KW - Cell Differentiation

KW - Myocardium

U2 - 10.1242/dmm.049834

DO - 10.1242/dmm.049834

M3 - SCORING: Journal article

C2 - 37272385

VL - 16

JO - DIS MODEL MECH

JF - DIS MODEL MECH

SN - 1754-8403

IS - 5

M1 - dmm049834

ER -