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Evaluation of the bystander effects in both mesenchymal stem cells and immunomodulation

Grant number: 13/23285-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2014
Effective date (End): January 31, 2017
Field of knowledge:Biological Sciences - Biology
Principal Investigator:Ricardo Ambrósio Fock
Grantee:Amanda Nogueira Pedro
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):15/18366-7 - Evaluation of the DNA damage in response to radiation-induced bystander effects on mesenchymal stem cells, BE.EP.PD

Abstract

Both in therapeutically strategies and in the accidental exposition to ionizing radiation, it has been dedicating efforts for the comprehension of the incident bystander effects. This effect translates the cellular responses received by the non-irradiated cells adjacent to directly irradiated cells. The signals from target cells can lead to decreasing of cell survival, causing cytogenetic damages, cell death, biochemical alterations and also modulating cellular differentiation, thus enabling the non-irradiated cells close to irradiated cells to develop adaptive responses, once in the absence of irradiated target cells, these responses would not occur. In general, these effects occur through both soluble factors releasing and cell-to-cell communication via gap-junctions, and they vary according to cell type, radiation dose, cellular microenvironment and immune responses under these conditions. The use of mesenchymal stem cells (MSC) has been clinically explored due to its differentiation capacity of forming cells from different tissues (reconstituting tissues after injury) and also because of its immunoregulatory ability that is involved mainly in T cell suppression, while its role in B cell modulation is still contradictory. Releasing of such soluble factors as interleukines, tumoral growth factor, gamma interferon, as well as intracellular calcium alterations and enzymatic production (e.g. metalloproteinases) have been identified as factors involved in the functions exerted by MSC. Therefore, considering the importance of a better comprehension related to the bystander effects, especially in vivo, and taking into consideration the current scenery of cellular therapies, where CTM derived from different tissues are being used as therapeutically co-adjuvants, the bystander effect in CTM in vitro and in vivo aims to add knowledge for the bystander mechanism generated from them, identifying its correlation to the immune system, inflammation process or radio induced damage, so that it can be clinically explored in order to modulated survival, differentiation or cell death.