Variation in the Incidence of Teratomas After the Transplantation of Nonhuman Primate ES Cells Into Immunodeficient Mice

Authors: Kishi, Yukiko; Tanaka, Yujiro; Shibata, Hiroaki; Nakamura, Shinichiro; Takeuchi, Koichi; Masuda, Shigeo; Ikeda, Tamako; Muramatsu, Shin-ichi; Hanazono, Yutaka

Source: Cell Transplantation, Volume 17, Number 9, 2008 , pp. 1095-1102(8)

Publisher: Cognizant Communication Corporation

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Abstract:

Embryonic stem (ES) cells have the ability to generate teratomas when transplanted into immunodeficient mice, but conditions affecting the generation remain to be elucidated. Nonhuman primate cynomolgus ES cells were transplanted into immunodeficient mice under different conditions; the number of transplanted cells, physical state (clumps or single dissociated cells), transplant site, differentiation state, and immunological state of recipient mice were all varied. The tumorigenicity was then evaluated. When cynomolgus ES cells were transplanted as clumps into the lower limb muscle in either nonobese diabetic/severe combined immunodeficiency (NOD/SCID) or NOD/SCID/γc^null (NOG) mice, teratomas developed in all the animals transplanted with 1 × 10⁵ or more cells, but were not observed in any mouse transplanted with 1 × 10³ cells. However, when the cells were transplanted as dissociated cells, the number of cells necessary for teratomas to form in all mice increased to 5 × 10⁵. When the clump cells were injected subcutaneously (instead of intramuscularly), the number also increased to 5 × 10⁵. When cynomolgus ES cell-derived progenitor cells (1 × 10⁶), which included residual pluripotent cells, were transplanted into the lower limb muscle of NOG or NOD/SCID mice, the incidence of teratomas differed between the strains; teratomas developed in five of five NOG mice but in only two of five NOD/SCID mice. The incidence of teratomas varied substantially depending on the transplanted cells and recipient mice. Thus, considerable care must be taken as to tumorigenicity.

Keywords: Nonhuman primate embryonic stem cells; NOD/SCID mouse; NOG mouse; Teratoma

Document Type: Research article

DOI: http://dx.doi.org/10.3727/096368908786991560

Publication date: 2008-09-01

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Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.

Variation in the Incidence of Teratomas After the Transplantation of Nonhuman Primate ES Cells Into Immunodeficient Mice

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