TY - JOUR
T1 - The evaluation of a tissue-engineered cardiac patch seeded with hips derived cardiac progenitor cells in a rat left ventricular model
AU - Matsuzaki, Yuichi
AU - Miyamoto, Shinka
AU - Miyachi, Hideki
AU - Sugiura, Tadahisa
AU - Reinhardt, James W.
AU - Yu-Chun, Chang
AU - Zbinden, Jacob
AU - Breuer, Christopher K.
AU - Shinoka, Toshiharu
N1 - Funding Information:
Funding:ThisresearchissupportedbyUS NationalInstitutesofHealth(NIH)grants: R01HL098228andGUNZEcoltd.Specifically GUNZEcoltdprovidedmaterialsupportthrough thecreationofthebiodegradablepatch.YMwas supportedbyDepartmentofDefence(DoD)and FundingawardfromUeharaMemorialFoundation (TokyoJapan)in2019.JWRwassupportedinpart bytheAmericanHeartAssociationunderAward Number18POST33990231.Thespecificrolesof theseauthorsarearticulatedinthe’author contributions’section.
Funding Information:
This research is supported by US National Institutes of Health (NIH) grants: R01HL098228 and GUNZE co ltd. Specifically GUNZE co ltd provided material support through the creation of the biodegradable patch. YM was supported by Department of Defence (DoD) and Funding award from Uehara Memorial Foundation (Tokyo Japan) in 2019. JWR was supported in part by the American Heart Association under Award Number 18POST33990231. The specific roles of these authors are articulated in the’author contributions’ section.
Publisher Copyright:
© 2020 Matsuzaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/6
Y1 - 2020/6
N2 - Background Ventricular septal perforation and left ventricular aneurysm are examples of potentially fatal complications of myocardial infarction. While various artificial materials are used in the repair of these issues, the possibility of associated infection and calcification is non-negligible. Cell-seeded biodegradable tissue-engineered patches may be a potential solution. This study evaluated the feasibility of a new left ventricular patch rat model to study neotissue formation in biodegradable cardiac patches. Methods Human induced pluripotent stem cell-derived cardiac progenitor cells (hiPS-CPCs) were cultured onto biodegradable patches composed of polyglycolic acid and a 50:50 poly (l-lactideco-ε-caprolactone) copolymer for one week. After culturing, patches were implanted into left ventricular walls of male athymic rats. Unseeded controls were also used (n = 10/group). Heart conditions were followed by echocardiography and patches were subsequently explanted at 1, 2, 6, and 9 months post-implantation for histological evaluation. Result Throughout the study, no patches ruptured demonstrating the ability to withstand the high pressure left ventricular system. One month after transplantation, the seeded patch did not stain positive for human nuclei. However, many new blood vessels formed within patches with significantly greater vessels in the seeded group at the 6 month time point. Echocardiography showed no significant difference in left ventricular contraction rate between the two groups. Calcification was found inside patches after 6 months, but there was no significant difference between groups. Conclusion We have developed a surgical method to implant a bioabsorbable scaffold into the left ventricular environment of rats with a high survival rate. Seeded hiPS-CPCs did not differentiate into cardiomyocytes, but the greater number of new blood vessels in seeded patches suggests the presence of cell seeding early in the remodeling process might provide a prolonged effect on neotissue formation. This experiment will contribute to the development of a treatment model for left ventricular failure using iPS cells in the future.
AB - Background Ventricular septal perforation and left ventricular aneurysm are examples of potentially fatal complications of myocardial infarction. While various artificial materials are used in the repair of these issues, the possibility of associated infection and calcification is non-negligible. Cell-seeded biodegradable tissue-engineered patches may be a potential solution. This study evaluated the feasibility of a new left ventricular patch rat model to study neotissue formation in biodegradable cardiac patches. Methods Human induced pluripotent stem cell-derived cardiac progenitor cells (hiPS-CPCs) were cultured onto biodegradable patches composed of polyglycolic acid and a 50:50 poly (l-lactideco-ε-caprolactone) copolymer for one week. After culturing, patches were implanted into left ventricular walls of male athymic rats. Unseeded controls were also used (n = 10/group). Heart conditions were followed by echocardiography and patches were subsequently explanted at 1, 2, 6, and 9 months post-implantation for histological evaluation. Result Throughout the study, no patches ruptured demonstrating the ability to withstand the high pressure left ventricular system. One month after transplantation, the seeded patch did not stain positive for human nuclei. However, many new blood vessels formed within patches with significantly greater vessels in the seeded group at the 6 month time point. Echocardiography showed no significant difference in left ventricular contraction rate between the two groups. Calcification was found inside patches after 6 months, but there was no significant difference between groups. Conclusion We have developed a surgical method to implant a bioabsorbable scaffold into the left ventricular environment of rats with a high survival rate. Seeded hiPS-CPCs did not differentiate into cardiomyocytes, but the greater number of new blood vessels in seeded patches suggests the presence of cell seeding early in the remodeling process might provide a prolonged effect on neotissue formation. This experiment will contribute to the development of a treatment model for left ventricular failure using iPS cells in the future.
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U2 - 10.1371/journal.pone.0234087
DO - 10.1371/journal.pone.0234087
M3 - Article
C2 - 32511282
AN - SCOPUS:85086253718
VL - 15
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e0234087
ER -