Human pluripotent stem cells are promising and potentially unlimited cell source for regenerative medicine;however, tumor formation is of major concern for cell therapy with pluripotent stem cells. Residual undifferentiated stem cells in preparations of stem cell derivatives, including cardiomyocyte differentiation cultures, have potential to proliferate and form teratoma upon transplantation, posing a major hurdle for safe cell therapy. Careful assessment of differentiation cultures and development of strategies to remove undifferentiated stem cells will facilitate qualification of final stem cell products for therapeutic use. In this study, we propose to develop sensitive, nanotechnology-based assays to detect residual undifferentiated cells, characterize cardiomyocyte differentiation cultures at various stages for their propensities to form teratomas, and evaluate strategies to selectively remove residual undifferentiated cells. Technology established in this study will be valuable for the development of novel cell therapy using human pluripotent stem cells.

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Human pluripotent stem cells have extensive proliferative capacity and can differentiate into many cell types including functional cardiomyocytes, representing promising cell source for regenerative medicine;however, teratoma formation is one of major safety concerns for clinical application. This study aims to develop sensitive nanotechnology-based assays to detect residual undifferentiated cells in differentiation cultures, characterize cardiomyocyte differentiation cells and evaluate strategies to prevent teratoma formation. Findings from this study will facilitate clinical translation of human pluripotent stem cells.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Exploratory/Developmental Grants (R21)
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Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
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Danthi, Narasimhan
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Emory University
Schools of Medicine
United States
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Rampoldi, Antonio; Crooke, Stephen N; Preininger, Marcela K et al. (2018) Targeted Elimination of Tumorigenic Human Pluripotent Stem Cells Using Suicide-Inducing Virus-like Particles. ACS Chem Biol 13:2329-2338
Jha, Rajneesh; Singh, Monalisa; Wu, Qingling et al. (2017) Downregulation of LGR5 Expression Inhibits Cardiomyocyte Differentiation and Potentiates Endothelial Differentiation from Human Pluripotent Stem Cells. Stem Cell Reports 9:513-527
Han, Jingjia; Wu, Qingling; Xia, Younan et al. (2016) Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation. Stem Cell Res 16:740-50
Preininger, Marcela K; Jha, Rajneesh; Maxwell, Joshua T et al. (2016) A human pluripotent stem cell model of catecholaminergic polymorphic ventricular tachycardia recapitulates patient-specific drug responses. Dis Model Mech 9:927-39
Han, Jingjia; Qian, Ximei; Wu, Qingling et al. (2016) Novel surface-enhanced Raman scattering-based assays for ultra-sensitive detection of human pluripotent stem cells. Biomaterials 105:66-76
Preininger, Marcela K; Singh, Monalisa; Xu, Chunhui (2016) Cryopreservation of Human Pluripotent Stem Cell-Derived Cardiomyocytes: Strategies, Challenges, and Future Directions. Adv Exp Med Biol 951:123-135
Jha, Rajneesh; Xu, Ren-He; Xu, Chunhui (2015) Efficient differentiation of cardiomyocytes from human pluripotent stem cells with growth factors. Methods Mol Biol 1299:115-31