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Research training in characterization, cryopreservation, sorting, homing and gene therapy using MSCs in experimental models: evaluation of cytokine therapy using TRAIL associated to MSCs for the treatment of glioblastoma on animal model

Grant number: 15/18964-1
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): January 11, 2016
Effective date (End): December 10, 2016
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Reproduction
Principal Investigator:Eunice Oba
Grantee:Carolina Nogueira de Moraes Maia
Supervisor: Jerónimo Blanco Fernández
Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Research place: Instituto de Química Avanzada de Cataluña (IQAC), Spain  
Associated to the scholarship:14/20447-2 - Comparative study of the immunophenotypic profile, differentiation potential, capacity of production of cytocines and cryopreservation of endometrial stromal cells of cattle during the oestrous cycle, BP.DR


Stem cells have attracted great interest because of their migratory capacity (homing) and previous researches were done focusing on their use for drug delivery associated with gene therapy, mainly on anticancer therapy and regenerative medicine. The use of stem cells for delivery of tumor necrosis factor-related apoptosis-inducing ligant (TRAIL) is a new and promising approach in animal models for the treatment of brain tumors resistant to chemotherapy and radiotherapy. In this context, Dr. Jeronimo Blanco accumulated considerable experience on the use of mesenchymal stromal cells for, tumor therapy and advanced techniques to evaluate their effect on tumor regression. Dr. Blanco has been leading a research group on the Department of Chemical and Biomolecular Nanotechnology at the Institute of Advanced Chemistry of Catalonia (iQAC), Barcelona, Spain since 1990, with scientific publication in journals of great JCR. In addition, the researcher headed a lot of projects with financial support related to the use o stem cells on the delivery of drugs that affect tumor growth. The supervision of the research in this collaboration will help provide additional learning opportunities and improvement to the PhD candidate in the areas of (1) Cell culture (MSCs and tumor cells), (2) Characterization of MSCs (cellular differentiation and immunophenotyping by flow cytometry (FC), (3) Cryopreservation, (4) Construction and validation of lentiviral vectors for gene therapy, (5) FC based cell sorting (6) Detection of factors soluble in the conditioned medium (8), study of cell homing in an animal model using advanced bioluminescence techniques. It is noteworthy that some of these techniques such as, cellular characterization, cryopreservation, sorting and detection of factors soluble in the conditioned medium will be extremely valuable for use in the current PhD proposal as they overlap with the thesis experimental strategy and will help resolve some technical difficulties encountered. The experience with research training will contribute to improvement quality and internationalization of our current and future work. In addition, the supervision of Dr Jeronimo Blanco, the collaboration of his team and the excellent infrastructure of the (iQAC) will contribute directly to improve the technical skills of the doctoral student which hopes to obtain more accurate results in the current research in Brazil. In addition, learning the use of genetic modification of MSCs (recombinant DNA technique with genes of interest, e.g., TRAIL) and procedures for accurate assessment of their migratory potential ex vivo and in vivo will open new perspectives for the realization of numerous studies in our laboratory, with direct collaborations with other research groups particularly in the state of São Paulo, for therapy of numerous disorders in Veterinary Medicine, with future possibility of extrapolation of results, including Human Medicine. (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)
NOGUEIRA DE MORAES, CAROLINA; MAIA, LEANDRO; DE OLIVEIRA, ELIANDRE; DE PAULA FREITAS DELL'AQUA, CAMILA; CHAPWANYA, ASPINAS; DA CRUZ LANDIM-ALVARENGA, FERNANDO; OBA, EUNICE. Shotgun proteomic analysis of the secretome of bovine endometrial mesenchymal progenitor/stem cells challenged or not with bacterial lipopolysaccharide. VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, v. 187, p. 42-47, . (15/01057-1, 15/18964-1, 14/20447-2)

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