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Regenerative medicine aiming at therapy for chronic degenerative diseases (cancer and diabetes)

Grant number: 16/05311-2
Support type:Research Projects - Thematic Grants
Duration: February 01, 2018 - January 31, 2023
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Mari Cleide Sogayar
Grantee:Mari Cleide Sogayar
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators:Eleazar Chaib ; Irene de Lourdes Noronha
Assoc. researchers: Adriano Barreto Nogueira ; Aline Ramos Maia Lobba ; Ana Claudia Oliveira Carreira Nishiyama ; André Fujita ; Antonio Carlos Campos de Carvalho ; Carlos de Ocesano Pereira ; Christian Bowman-Colin ; Fernando Henrique Lojudice da Silva ; Fernando Janczur Velloso ; Isa Dietrich ; Jose Alexandre Marzagão Barbuto ; José Mauro Granjeiro ; Lauren Camargo ; Luciana Oliveira Cruz ; Luiz Augusto Carneiro D'Albuquerque ; Makoto Noda ; Marcos Angelo Almeida Demasi ; Maria Angelica Miglino ; Maria Emilia Zenteno ; Maria Lucia Cardillo Corrêa Giannella ; Marina Trombetta Lima ; Marluce da Cunha Mantovani ; Michael Weller ; Milton Yutaka Nishiyama Junior ; Miriam Lemos ; Patricia Rieken Macedo Rocco ; Pranela Rameshwar ; Ricardo Garcia Corrêa ; Rubens Belfort Mattos Junior ; Sandra Helena Poliselli Farsky ; Sheila Maria Brochado Winnischofer ; Suely Kazue Nagahashi Marie ; Tracy Cannon Grikscheit ; Vinicius Rocha Santos ; Vitor Antonio Fortuna ; William Stetler Stevenson


NUCEL was structured as a translational research Center, having as its mission to act in the Cell and Molecular Therapy area, starting from basic Science centered on molecular mechanisms of cell proliferation and differentiation control and the origin of malignancy to transform the knowledge generated on the bench into products and processes which may be utilized both in medical, odontological, veterinary and agro-business clinical practice, and in the pharmaceutical/biotechnological sector, aiming at the production of national biopharmaceuticals to be utilized in the management and cure of degenerative and non-degenerative diseases. The Team, composed of more than 50 members, actively works in the new Regenerative Medicine, which aims to repair, reconstruct, regenerate and remodel tissues and organs, being based on three main pillars: stem cells, extracellular matrix/scaffolds and peptide growth and differentiation factors. In the last few years, the incidence of chronic-degenerative diseases, such as cancer and diabetes mellitus, have significantly increased due to ageing of the Brazilian and World population, sedentarism, feeding habits, obesity and cardio-vascular diseases. Bone fractures and lesions have increased in the young population due to under-nutrition and urban violence. In this Project, two different types of cancer are focused, namely: glioblastoma multiform, due to its high degree of lethality and localization to the central nervous system, and mammary carcinoma, due to its high incidence and mortality rates in women. Utilizing a multiple approach (genomics, transcriptomics and functional genomics), we expect to find new molecular targets to be used as markers for early diagnosis and prognosis and as therapeutic tools for these neoplasia. Aiming at minimizing the risk of death and commitment of the quality of life of unstable/labile type 1 Diabetes mellitus (DM1) patients, the following strategic objectives are proposed: a) transplantation of isolated pancreatic islets; b) differentiation of embryonic stem cells into insulin-producing cells (IPCs); c) encapsulation of isolated islets and IPCs, thereby avoiding the use of immunossupressors; d) pancreas decellularization, generating a decellularized and functionalized pancreatic matrix/scaffold; e) final maturation of IPCs in the decellularized matrix prior to their implant into animals rendered diabetic. In consonance with the Research, Development and Innovation public policies of the Brazilian government, particularly in the areas of Biotechnology and Regenerative Medicine, we also propose to utilize last generation eukaryotic heterologous expression systems to produce recombinant human proteins of strategic therapeutic interest (Biopharmaceuticals), such as: PDGF-BB, TGF-²1 e TGF-²3, VEGF-A, R-Espondina1 and BMP-7, in agreement with the demand for serum-free and other animal components-free Regenerative Cell Therapy, in the most advanced state of the art. In pursuing these Goals, we hope to continue to form highly qualified people to act in the basic and clinical areas of Cell and Molecular Therapy, in the nascent field of Regenerative Medicine and in the long-sought bridge between the University and the Business Health sectors. (AU)

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)
VELLOSO, FERNANDO J.; TROMBETTA-LIMA, MARINA; ANSCHAU, VALESCA; SOGAYAR, MARI C.; CORREA, RICARDO G. NOD-like receptors: major players (and targets) in the interface between innate immunity and cancer. BIOSCIENCE REPORTS, v. 39, n. 4 APR 30 2019. Web of Science Citations: 0.
ASSIS-RIBAS, THAIS; FORNI, MARIA FERNANDA; BROCHADO WINNISCHOFER, SHEILA MARIA; SOGAYAR, MARI CLEIDE; TROMBETTA-LIMA, MARINA. Extracellular matrix dynamics during mesenchymal stem cells differentiation. Developmental Biology, v. 437, n. 2, p. 63-74, MAY 15 2018. Web of Science Citations: 7.

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