Keun-Tae Kim1, Ho-Chang Jeong1, C-Yoon Kim2, Eun-Young Kim3, Si-Hyun Heo2, Seung-Ju Cho1, Ki-Sung Hong4, Hyuk-Jin Cha5. 1. Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, Republic of Korea. 2. Department of Medicine, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea. 3. Stem cell Research Center, Jeju National University, Jeju, Jeju Special Self-Governing Province, Republic of Korea; Mirae Cell Bio Co. LTD, Seoul, Republic of Korea. 4. Department of Medicine, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea. Electronic address: stemness@gmail.com. 5. Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, Republic of Korea. Electronic address: hjcha@sogang.ac.kr.
Abstract
BACKGROUND: Risk of teratoma formation during human pluripotent stem cell (hPSC)-based cell therapy is one of the technical hurdles that must be resolved before their wider clinical application. To this end, selective ablation of undifferentiated hPSCs has been achieved using small molecules whose application should be safe for differentiated cells derived from the hPSCs. OBJECTIVE: However, the functional safety of such small molecules in the cells differentiated from hPSCs has not yet been extensively validated. METHOD: We used the survivin inhibitor YM155, which induced highly selective cell death of hPSCs for ablating undifferentiated hESCs after differentiation to human mesenchymal stem cells (hMSCs) and examined whether hMSCs remained fully functional after being exposed by YM155. RESULTS: We demonstrated that human mesenchymal stem cells (hMSCs) derived from human embryonic stem cells (hESCs) remained fully functional in vitro and in vivo, while hESCs were selectively ablated. CONCLUSION: These results suggest that a single treatment with YM155 after differentiation of hMSCs would be a valid approach for teratoma-free cell therapy.
BACKGROUND: Risk of teratoma formation during human pluripotent stem cell (hPSC)-based cell therapy is one of the technical hurdles that must be resolved before their wider clinical application. To this end, selective ablation of undifferentiated hPSCs has been achieved using small molecules whose application should be safe for differentiated cells derived from the hPSCs. OBJECTIVE: However, the functional safety of such small molecules in the cells differentiated from hPSCs has not yet been extensively validated. METHOD: We used the survivin inhibitor YM155, which induced highly selective cell death of hPSCs for ablating undifferentiated hESCs after differentiation to human mesenchymal stem cells (hMSCs) and examined whether hMSCs remained fully functional after being exposed by YM155. RESULTS: We demonstrated that human mesenchymal stem cells (hMSCs) derived from human embryonic stem cells (hESCs) remained fully functional in vitro and in vivo, while hESCs were selectively ablated. CONCLUSION: These results suggest that a single treatment with YM155 after differentiation of hMSCs would be a valid approach for teratoma-free cell therapy.