Citations 2
Human Stem Cell–Derived Cardiomyocytes Integrate Into the Heart of Monkeys With Right Ventricular Pressure Overload
Scholz, Jodi A. , Secreto, Frank J., Wobig, Joan, Kurian, Joe R, Hagen, Clint , Zinnen, Alexandra D. , Vu, Don, Johnson, Steven J., Cetta, Frank , Qureshi, M. Yasir , Reams, Rachel Y., Cannon, Bryan C. , Heyer, Christina M., Chang, Min‐Hwang , Fadra, Numrah, Coonen, Jennifer , Simmons, Heather A. , Mejía, Andrés , Hayes, Jennifer M. , Basu, Puja , Capuano, Saverio , Bondarenko, Viktoriya, Metzger, Jeanette M. , Nelson, Timothy J., Scholz, Jodi, Qureshi, Muhammad Y , Cannon, Bryan, Emborg, Marina E , Vu, Don, Johnson, Steven J., Nelson, Timothy J.
Cell Transplantation | November 2, 2024 | Volume: 33 | Issue: No issue available | Pages: No page available
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.
Biomarkers for Predicting Abiraterone Treatment Outcome and Selecting Alternative Therapies in Castration‐Resistant Prostate Cancer
Gao, Huanyao , Kim, Wootae , Scholz, Jodi A. , Yu, Jia , Qin, Bo , Zhuang, Yongxian , Tan, Winston , Bryce, Alan H. , Weinshilboum, Richard M. , Wang, Liewei , Xie, Fang , Bryce, Alan H , Kim, Wootae , Qin, Sisi , Zhang, Huan , Gu, Yayun , Kalari, Krishna R. , Sinnwell, Jason P. , Xie, Fang , Yin, Ping , Wei, Lixuan , Weinshilboum, Richard M.
Clinical Pharmacology & Therapeutics | March 15, 2022 | Volume: 111 | Issue: 6 | Pages: 1296-1306
Approximately one‐third of patients with metastatic castration‐resistant prostate cancer (CRPC) exhibited primary abiraterone resistance. To identify alternative treatment for abiraterone nonresponders, we performed drug discovery analyses using the L1000 database using differentially expressed genes identified in tumor biopsies and patient‐derived xenograft (PDX) tumors between abiraterone responders and nonresponders enrolled in PROMOTE trial. This approach identified 3 drugs, including topoisomerase II (TOP2) inhibitor mitoxantrone, CDK4/6 inhibitor palbociclib, and pan‐CDK inhibitor PHA‐793887. These drugs significantly suppressed the growth of abiraterone‐resistant cell lines and PDX models. Moreover, we identified 11 genes targeted by all 3 drugs that were associated with worse outcomes in both the PROMOTE and Stand Up To Cancer cohorts. This 11‐gene panel might also function as biomarkers to select the 3 alternative therapies for this subgroup of patients with CRPC, warranting further clinical investigation.