The evaluation of a tissue-engineered cardiac patch seeded with hips derived cardiac progenitor cells in a rat left ventricular model

Yuichi, Matsuzaki, Shinka, Miyamoto, Hideki, Miyachi, Tadahisa, Sugiura, James W., Reinhardt, Chang, Yu-Chun, Jacob, Zbinden, Christopher K., Breuer, Toshiharu, Shinoka

PLOS ONE |

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-negligi- ble. 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 for- mation in biodegradable cardiac patches. Methods Human induced pluripotent stem cell-derived cardiac progenitor cells (hiPS-CPCs) were cul- tured onto biodegradable patches composed of polyglycolic acid and a 50:50 poly (l-lactide- co-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. Echocardi- ography 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 ven- tricular 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 sug- gests the presence of cell seeding early in the remodeling process might provide a pro- longed 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.