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 - der Sluis, Verena Horneffer Van
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 - Publisher Copyright:
© 2023. Published by The Company of Biologists Ltd.
PY - 2023/5
Y1 - 2023/5
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 - Cardiac repair
KW - Cell transplantation
KW - Chronic injury model
KW - Engineered heart tissue
KW - Heart failure
KW - Tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=85162288149&partnerID=8YFLogxK
U2 - 10.1242/dmm.049834
DO - 10.1242/dmm.049834
M3 - Article
C2 - 37272385
AN - SCOPUS:85162288149
SN - 1754-8403
VL - 16
JO - DMM Disease Models and Mechanisms
JF - DMM Disease Models and Mechanisms
IS - 5
M1 - dmm049834
ER -
