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Migration and effect of human mesenchymal stem cells transfected with murine IL-12 gene in the tumoral microenvironment of murine melanoma and breast cancer

Abstract

Mesenchymal Stem Cells (MSCs) are defined as multipotent stem cells with the ability of self-renew and the potential to differentiate in vitro into at least three distinct lineages with embryonic mesodermal origin. Constitute a reservoir found in the connective tissue of most organs and are involved in maintenance and repair of tissues throughout the life of an individual. Umbilical cord, dental pulp, orbicular oris muscle, adipose tissue, endometrium, menstrual blood and fallopian tubes are very rich sources of MSCs. The immunomodulatory effect of MSCs and the absence of rejection in transplantation, including xenotransplantation, corroborates with the idea that these cells can be used in heterologous transplants in the future. It is known that MSCs secrete a number of factors that can have angiogenic and immunomodulatory effects, including xenograft transplants of human MSCs in animal models. They also have the ability to recognize and inflammatory processes and to direct themselves to a tissue that needs to be repaired - a process called "homing". The lack of basic knowledge about the biology of MSCs, including survival, migration, differentiation and integration when transplanted remains an poorly understood. The role of MSCs in cancer is still controversial; however, it has been shown that stem cells migrate specifically to the tumor tissues when transferred to animals developing tumors Besides that, these cells may have immunomodulatory effect and secrete bioactive factors that can be amplified with transfection of specific genes. Studies show that Interleukin 12 (IL-12) in systemic treatment has powerful antitumor effect in vivo, activating cells of the immune response and inducing a protective antitumor response, but at the same time, inducing strong undesirable side effects due to high doses in an attempt counter the intense and rapid degradation of this cytokine that occurs in vivo. Intratumoral expression of IL-12 has shown good effects in some experimental models. The combination of cell therapy based on MSCs, along with gene therapy, can result in a good therapeutic trial against tumor growth. Transfecting MSCs isolated from the human female reproductive tract with the plasmid containing the murine IL-12 gene, we expect to see the overexpression of this molecule in the tumor microenvironment, and control the development of melanoma and syngeneic murine adenocarcinoma. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
JAZEDJE, T.; RIBEIRO, A. L.; PELLATI, M.; DE SIQUEIRA BUENO, H. M.; NAGATA, G.; TRIERVEILER, M.; RODRIGUES, E. G.; ZATZ, M.. Human Mesenchymal Stromal Cells Transplantation May Enhance or Inhibit 4T1 Murine Breast Adenocarcinoma through Different Approaches. STEM CELLS INTERNATIONAL, v. 2015, p. 11-pg., . (11/51648-5)
JAZEDJE, T.; RIBEIRO, A. L.; PELLATI, M.; DE SIQUEIRA BUENO, H. M.; NAGATA, G.; TRIERVEILER, M.; RODRIGUES, E. G.; ZATZ, M.. Human Mesenchymal Stromal Cells Transplantation May Enhance or Inhibit 4T1 Murine Breast Adenocarcinoma through Different Approaches. STEM CELLS INTERNATIONAL, . (11/51648-5)

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