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Sufficiency for inducible Caspase-9 safety switch in human pluripotent stem cells and disease cells
- Source :
- Gene Therapy. 27:525-534
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have promising potential for opening new avenues in regenerative medicine. However, since the tumorigenic potential of undifferentiated pluripotent stem cells (PSCs) is a major safety concern for clinical transplantation, inducible Caspase-9 (iC9) is under consideration for use as a fail-safe system. Here, we used targeted gene editing to introduce the iC9 system into human iPSCs, and then interrogated the efficiency of inducible apoptosis with normal iPSCs as well as diseased iPSCs derived from patients with acute myeloid leukemia (AML-iPSCs). The iC9 system induced quick and efficient apoptosis to iPSCs in vitro. More importantly, complete eradication of malignant cells without AML recurrence was shown in disease mouse models by using AML-iPSCs. In parallel, it shed light on several limitations of the iC9 system usage. Our results suggest that careful use of the iC9 system will serve as an important countermeasure against posttransplantation adverse events in stem cell transplantation therapies.
- Subjects :
- 0301 basic medicine
Myeloid leukemia
Biology
Embryonic stem cell
Regenerative medicine
Transplantation
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Genome editing
Apoptosis
030220 oncology & carcinogenesis
Genetics
Cancer research
Molecular Medicine
Stem cell
Induced pluripotent stem cell
Molecular Biology
Subjects
Details
- ISSN :
- 14765462 and 09697128
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Gene Therapy
- Accession number :
- edsair.doi...........d39647f614defaddfa848b60cc1b6561