Inducible Caspase-9 Suicide Gene Under Control of Endogenous Oct4 to Safeguard Mouse and Human Pluripotent Stem Cell Therapy

Overview

Journal Mol Ther Methods Clin Dev

Publisher Cell Press

Date 2022 Mar 1

PMID 35229007

Authors

Yang Liu

Yang Yang

Yangyang Suo

Chuan Li

Min Chen

Shuwen Zheng

Hao Li

Chengcheng Tang

Nana Fan

Ting Lan

Jizeng Zhou

Yingying Li

Jiaowei Wang

Huangyao Chen

Qingjian Zou

Liangxue Lai

Affiliations

Soon will be listed here.

Abstract

Pluripotent stem cells (PSCs) are promising in regenerative medicine. A major challenge of PSC therapy is the risk of teratoma formation because of the contamination of undifferentiated stem cells. Constitutive promoters or endogenous SOX2 promoters have been used to drive inducible caspase-9 () gene expression but cannot specifically eradicate undifferentiated PSCs. Here, we inserted gene into the endogenous OCT4 locus of human and mouse PSCs without affecting their pluripotency. A chemical inducer of dimerization (CID), AP1903, induced activation, which led to the apoptosis of specific undifferentiated PSCs and . Differentiated cell lineages survived because of the silence of the endogenous gene. Human and mouse PSCs were controllable when CID was administrated within 2 weeks after PSC injection in immunodeficient mice. However, an interval longer than 2 weeks caused teratoma formation and mouse death because a mass of somatic cells already differentiated from the PSCs. In conclusion, we have developed a specific and efficient PSC suicide system that will be of value in the clinical applications of PSC-based therapy.

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