Immunologic targeting of CD30 eliminates tumourigenic human pluripotent stem cells, allowing safer clinical application of hiPSC-based cell therapy

Scientific Reports
Nagako SougawaYoshiki Sawa

Abstract

Induced pluripotent stem cells (iPSCs) are promising candidate cells for cardiomyogenesis in the failing heart. However, teratoma/tumour formation originating from undifferentiated iPSCs contaminating the graft is a critical concern for clinical application. Here, we hypothesized that brentuximab vedotin, which targets CD30, induces apoptosis in tumourigenic cells, thus increasing the safety of iPSC therapy for heart failure. Flow cytometry analysis identified consistent expression of CD30 in undifferentiated human iPSCs. Addition of brentuximab vedotin in vitro for 72 h efficiently induced cell death in human iPSCs, associated with a significant increase in G2/M phase cells. Brentuximab vedotin significantly reduced Lin28 expression in cardiomyogenically differentiated human iPSCs. Transplantation of human iPSC-derived cardiomyocytes (CMs) without treatment into NOG mice consistently induced teratoma/tumour formation, with a substantial number of Ki-67-positive cells in the graft at 4 months post-transplant, whereas iPSC-derived CMs treated with brentuximab vedotin prior to the transplantation did not show teratoma/tumour formation, which was associated with absence of Ki-67-positive cells in the graft over the same period. Th...Continue Reading

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Citations

Nov 17, 2019·International Journal of Molecular Sciences·Heng Liang Tan, Andre Choo
Sep 21, 2018·Tissue Engineering. Part C, Methods·Katsuhisa MatsuuraTatsuya Shimizu
Jun 7, 2018·Nature Reviews. Cardiology·Hisayuki HashimotoRhonda Bassel-Duby
Jun 26, 2020·Scientific Reports·Keisuke SekineHideki Taniguchi
Mar 15, 2019·Stem Cell Research & Therapy·Jolanta GoreckaAlan Dardik
Jul 3, 2021·Journal of Personalized Medicine·Julia DahlkeAxel Schambach
Aug 10, 2021·Frontiers in Immunology·Olga ZimmermannovaCarlos-Filipe Pereira
Oct 3, 2020·Cell Stem Cell·Shinya Yamanaka
Nov 18, 2021·Bioengineered·Li ZengSheng-Kang Luo

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Methods Mentioned

BETA
transfection
FACS
flow cytometry
PCR

Software Mentioned

BD FACSDiva

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis