The Tumorigenicity of Human Embryonic Stem Cells

Barak Blum*, Nissim Benvenisty

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

363 Scopus citations


Human embryonic stem cells (HESCs) are the in vitro descendants of the pluripotent inner cell mass (ICM) of human blastocyst stage embryos. HESCs can be kept undifferentiated in culture or be differentiated to tissues representing all three germ layers, both in vivo and in vitro. These properties make HESC-based therapy remarkably appealing for the treatment of various disorders. Upon transplantation in vivo, undifferentiated HESCs rapidly generate the formation of large tumors called teratomas. These are benign masses of haphazardly differentiated tissues. Teratomas also appear spontaneously in humans and in mice. When they also encompass a core of malignant undifferentiated cells, these tumors are defined as teratocarcinomas. These malignant undifferentiated cells are termed embryonic carcinoma (EC), and are the malignant counterparts of embryonic stem cells. Here we review the history of experimental teratomas and teratocarcinomas, from spontaneous teratocarcinomas in mice to induced teratomas by HESC transplantation. We then discuss cellular and molecular aspects of the tumorigenicity of HESCs. We also describe the utilization of HESC-induced teratomas for the modeling of early human embryogenesis and for modeling developmental diseases. The problem of HESC-induced teratomas may also impede or prevent future HESC-based therapies. We thus conclude with a survey of approaches to evade HESC-induced tumor formation.

Original languageAmerican English
Title of host publicationAdvances in Cancer Research
EditorsGeorge Woude, George Klein
Number of pages26
StatePublished - 2008

Publication series

NameAdvances in Cancer Research
ISSN (Print)0065-230X

Bibliographical note

Funding Information:
We thank Yoav Mayshar and Rina Klinov for critically reading the manuscript and Tamar Golan‐Lev for assistance with preparation of the figures. This work was partially supported by funds from Bereshit Consortium, the Israeli Ministry of Trade and Industry (Grant number 37675), and by the European Community (ESTOOLS, Grant number 018739).


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