Human Stem Cell–Derived Cardiomyocytes Integrate Into the Heart of Monkeys With Right Ventricular Pressure Overload

Autor: Jodi Scholz, Frank J. Secreto, Joan Wobig, Joe Kurian, Clint Hagen, Alexandra Zinnen, Don Vu, Steven J. Johnson, Frank Cetta, Yasir Qureshi, Rachel Reams, Bryan Cannon, Christina M. Heyer, Minhwang Chang, Numrah Fadra, Jennifer Coonen, Heather A. Simmons, Andres Mejia, Jennifer M. Hayes, Puja Basu, Saverio Capuano, Viktoriya Bondarenko, Jeanette M. Metzger, Timothy J. Nelson, Marina E. Emborg
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cell Transplantation, Vol 33 (2024)
Druh dokumentu: article
ISSN: 1555-3892
09636897
DOI: 10.1177/09636897241290367
Popis: Cardiac ventricular pressure overload affects patients with congenital heart defects and can cause cardiac insufficiency. Grafts of stem cell–derived cardiomyocytes are proposed as a complementary treatment to surgical repair of the cardiac defect, aiming to support ventricular function. Here, we report successful engraftment of human induced pluripotent stem cell–derived cardiac lineage cells into the heart of immunosuppressed rhesus macaques with a novel surgical model of right ventricular pressure overload. The human troponin+ grafts were detected in low-dose (2 × 10 6 cells/kg) and high-dose (10 × 10 6 cells/kg) treatment groups up to 12 weeks post-injection. Transplanted cells integrated and progressively matched the organization of the surrounding host myocardium. Ventricular tachycardia occurred in five out of 16 animals receiving cells, with episodes of incessant tachycardia observed in two animals; ventricular tachycardia events resolved within 19 days. Our results demonstrate that grafted cardiomyocytes mature and integrate into the myocardium of nonhuman primates modeling right ventricular pressure overload.
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