Sufficiency for inducible Caspase-9 safety switch in human pluripotent stem cells and disease cells

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, inducib...

Full description

Saved in:
Bibliographic Details
Published in:Gene therapy 2019-11, Vol.27 (10-11), p.525-534
Main Authors: Nishimura, Toshinobu, Xu, Haojun, Iwasaki, Masayuki, Karigane, Daiki, Saavedra, Brandon, Takahashi, Yusuke, Suchy, Fabian P., Monobe, Shinichiro, Martin, Renata M., Ohtaka, Manami, Nakanishi, Mahito, Burrows, Scott R., Cleary, Michael L., Majeti, Ravindra, Shibuya, Akira, Nakauchi, Hiromitsu
Format: Article
Language:English
Subjects:
13/2
42/100
42/41
59/5
631/532/1542
631/61/201/2110
Acute myeloid leukemia
Adverse events
Animal models
Apoptosis
Biomedical and Life Sciences
Biomedicine
Brief Communication
Caspase-9
Cell Biology
Embryo cells
Embryonic stem cells
Gene Expression
Gene Therapy
Genetic aspects
Genome editing
Health aspects
Human Genetics
Myeloid leukemia
Nanotechnology
Pluripotency
Proteases
Regenerative medicine
Stem cell transplantation
Stem cells
Transplantation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0969-7128
1476-5462
DOI:10.1038/s41434-020-0179-z