Tumorigenicity risk of iPSCs in vivo: nip it in the bud


Review

. 2022 Feb 3;5(1):pbac004.


doi: 10.1093/pcmedi/pbac004.


eCollection 2022 Mar.

Affiliations

Item in Clipboard

Review

Chaoliang Zhong et al.


Precis Clin Med.


.

Abstract

In 2006, Takahashi and Yamanaka first created induced pluripotent stem cells from mouse fibroblasts via the retroviral introduction of genes encoding the transcription factors Oct3/4, Sox2, Klf44, and c-Myc. Since then, the future clinical application of somatic cell reprogramming technology has become an attractive research topic in the field of regenerative medicine. Of note, considerable interest has been placed in circumventing ethical issues linked to embryonic stem cell research. However, tumorigenicity, immunogenicity, and heterogeneity may hamper attempts to deploy this technology therapeutically. This review highlights the progress aimed at reducing induced pluripotent stem cells tumorigenicity risk and how to assess the safety of induced pluripotent stem cells cell therapy products.


Keywords:

chemical-induced reprogramming; drug-inducible suicide system; induced pluripotent stem cells (iPSCs); regenerative medicine; reprogramming transcription factors; tumorigenicity.

Figures


Figure 1.



Figure 1.

Mechanism of iCASP9’s safety switch. The AAVS1 TALEN and the donor constructs are delivered to cells via plasmid transfection. Then, the antibiotic-resistant cells are selected. Next, the administration of APs leads to the dimerization of FKBP12-F36V. As a result, caspase9 and the downstream effector caspases, such as caspase-3 and caspase-7, are activated, which leads to cell apoptosis.


Figure 2.



Figure 2.

Schematic diagram of methods for purifying iPSC samples. (A) LCST behavior of PDEGMA. iPSCs are cultured on the polymer at 37°C for 5 days and grow into colonies on the layer. By cooling the temperature to 22°C, iPSC colonies detach from the layer while differentiated cells remain on the layer. (B) After incubation with SpheriTech beads coated with affinity antibody, the target cells in a hetergenous cell suspension bind to the beads. Label-free target cells are eluted from the beads by trypsin and affinity antibodies still stay attached to the beads. (C) Compared with SpheriTech beads, antibodies or magnetic particles attached to the target cells may influence the cells for positive selection by MACS. HCS: heterogeneous cell suspension; TCs: target cells.


Figure 3.



Figure 3.

Strategies for reducing tumorigenesis risk.

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