2010. Vol. 52, N 10, p. 853–857
CHARACTERISTIC OF TUMORS DEVELOPED AFTER TRANSPLANTATION OF TRANSGENIC GFP-POSITIVE C57BL/6 MICE BONE-MARROW MESENCHYMAL STEM SELLS TO mdx MICE MUSCLE

V. M. Mikhailov,1 E. V. Kaminskaja,1 V. B. Popov,1 S. N. Kuzovatov,1 N. S. Skripkina,2
G. B. Kosjakova,3 A. M. Zaichik,4 T. M. Grinchuk,1 N. N. Nikolsky 1

1 Institute of Cytology RAS, St. Petersburg, 2 St. Petersburg’s Pathologic-Anatomical Bureau, 3 Research Institute of Agree-Cultural Animals Genetics, and 4 Postgraduate Medical Academy, St. Petersburg;
e-mail: vmikhailov@mail.cytspb.rssi.ru

The purpose of the study was the morphological and histochemical characteristies of differentiation of tumors developed after transplantation of GFP-positive mesenchymal bone-marrow stem cells (MSC) of transgenic mice C57BL/6 into M. quadriceps femoris of mdx mice. The tumors occurred only after transplantation of MSCs of 43—45th passages and did not arise after transplantation of MSCs of the 15th passage. No tumors developed also after transplantation of MSCs of 43—45th passages into muscle of C57BL/6 mice. The average weight of tumors appeared in 4 mdx mice studied was 1.3 ± 0.5 g. All four tumors were classified as mesenchymomas because they originated from mesenchymal stem cells. Most of the periphery of the tumors was classified as fibrosarcomas with mitotic index 0.9 ± 0.1 %. The central parts of tumors had areas with epithelial like morphology of cells. Such cells showed positive reactivity for alcyan blue staining at pH 2.5, which indicated chondrocyte nature of the cells. No mitosis was observed in epithelial like cells. In the tumors, there were also areas with bone trabeculae containing megacaryocytes and foci of myeloid and erythrocyte hematopoiesis. There were also areas with neuronal and glial cells, and accumulations of adipocytes. One of the tumors was classified as a round cells sarcoma. The observed types of tumor cell differentiation in vivo were in accordance with described in literature types of MSCs differentiation after induction in vitro with special inductors. The spectrum of in vivo differentiation of transgenic GFP-positive MSCs after transplantation to mdx mice was broader than the spectrum of in vivo differentiation of transfected or transformed in vitro adult MSCs after transplantation to immunodeficient mice and mdx mice.

Key words:  GFP-positive mesenchymal stem cells, transplantation, mdx mice, tumors, differentiation


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