A novel mouse model that closely mimics human uterine leiomyomas

Capsule:
Ex vivo expanded myoma cells or transformed and immortalized by SV40ER lose in vivo tumorigenicity. Injections of uncultured primary myoma cells produce stable xenografts with unique similarity to human fibroids.

Authors:
Michael Drosch, M.Sc., Jörn Bullerdiek, XX, Thomas M. Zollner, M.D., Florian Prinz, M.D., Ph.D., Markus Koch, Ph.D., Nicole Schmidt, Ph.D.

Volume 99, Issue 3, Pages 927-935.e6, 1 March 2013

Abstract:

Objective:
To develop a predictive mouse model for uterine fibroids.

Design:
Human fibroid cells xenografted to immunodeficient mice.

Setting:
University and industrial research center.

Animals:
Immunodeficient scid/beige mice.

Interventions:
Subcutaneous and intra-uterine injection of fibroid-derived cells, SV40 transformation of primary cells by lentiviral transduction, proliferation determined by immunohistochemistry, FISH.

Main outcomes:
Characterization of primary and immortalized cells by Western blot and soft agar assay, determination of in vivo tumorigenicity, comparative histology and immunohistochemistry, FISH.

Results:
Tumorigenicity of primary myoma cells disappears upon in vitro culture. Transformation and immortalization does not restore or conserve the in vivo growth potential of cultured cells. Injection of primary cells into myometrium of mice leads to xenografts with a leiomyoma-like histology.

Conclusion:
Primary myoma cells are suited to generate fibroid-like xenografts for studying pathogenesis without genetic modifications. In contrast, in vitro culture abolishes transplantability and neither transformation nor immortalization is sufficient to restore tumorigenic capacity.

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