The tumorigenicity of diploid and aneuploid human pluripotent stem cells

Barak Blum*, Nissim Benvenisty

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

114 Scopus citations

Abstract

Human embryonic stem cells (HESCs) and induced pluripotent stem cells (HiPSCs) offer an immense potential as a source of cells for regenerative medicine. However, the ability of undifferentiated HESCs and HiPSCs to produce tumors in vivo presents a major obstacle for the translation of this potential into clinical reality. Therefore, characterizing the nature of HESC- and HiPSC-derived tumors, especially their malignant potential, is extremely important in order to evaluate the risk involved in their clinical use. Here we review recent observations on the tumorigenicity of human pluripotent stem cells. We argue that diploid, early passage, HESCs produce benign teratomas without undergoing genetic modifications. Conversely, HESCs that acquired genetic or epigenetic changes upon adaptation to in vitro culture can produce malignant teratocarcinomas. We discuss the molecular mechanisms of HESC tumorigenicity and suggest approaches to prevent tumor formation from these cells. We also discuss the differences in the tumorigenicity between mouse embryonic stem cells (MESCs) and HESCs, and suggest methodologies that may help to identify cellular markers for culture adapted HESCs.

Original languageAmerican English
Pages (from-to)3822-3830
Number of pages9
JournalCell Cycle
Volume8
Issue number23
DOIs
StatePublished - 1 Dec 2009

Bibliographical note

Funding Information:
We are grateful to all the members of the Benvenisty lab for their support, especially Tamar Golan-Lev for providing the karyotype of the cells, and Yoav Mayshar for countless discussions and suggestion. We thank Justin Annes for his help with the writing of the manuscript. B.B. also acknowledges Ittai Ben-Porath for unknowingly provoking ideas. This work was partially supported by funds from the European Community (ESTOOLS, Grant number 018739) and the Herbert Cohn Chair in Cancer Research. We gratefully acknowledge support for this project provided by a grant from Legacy Heritage Fund of New York.

Keywords

  • Culture adaptation
  • Human embryonic stem cells
  • Induced pluripotent stem cells
  • Teratocarcinoma
  • Teratoma

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