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KMID : 0624620220550030142
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BMB Reports
2022 Volume.55 No. 3 p.142 ~ p.147
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Monoclonal antibody K312-based depletion of pluripotent cells from differentiated stem cell progeny prevents teratoma formation
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Park Jong-Jin
Lee Dong-Gwang
Lee Na-Geum
Kwon Min-Gi
Son Yeon-Sung
Son Mi-Young
Bae Kwang-Hee
Lee Jang-Wook
Park Jong-Gil
Lee Nam-Kyung
Min Jeong-Ki
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Abstract
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Human pluripotent stem cells (PSCs) have been utilized as a promising source in regenerative medicine. However, the risk of teratoma formation that comes with residual undifferentiated PSCs in differentiated cell populations is most concerning in the clinical use of PSC derivatives. Here, we report that a monoclonal antibody (mAb) targeting PSCs could distinguish undifferentiated PSCs, with potential teratoma-forming activity, from differentiated PSC progeny. A panel of hybridomas generated from mouse immunization with H9 human embryonic stem cells (hESCs) was screened for ESC-specific binding using flow cytometry. A novel mAb, K312, was selected considering its high stem cell-binding activity, and this mAb could bind to several human induced pluripotent stem cells and PSC lines. Cell-binding activity of K312 was markedly decreased as hESCs were differentiated into embryoid bodies or by retinoic acid treatment. In addition, a cell population negatively isolated from undifferentiated or differentiated H9 hESCs via K312 targeting showed a significantly reduced expression of pluripotency markers, including Oct4 and Nanog. Furthermore, K312-based depletion of pluripotent cells from differentiated PSC progeny completely prevented teratoma formation. Therefore, our findings suggest that K312 is utilizable in improving stem cell transplantation safety by specifically distinguishing residual undifferentiated PSCs.
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KEYWORD
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Cell-surface marker, Monoclonal antibody, Pluripotent stem cells, Stem cell differentiation, Teratoma
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