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

• Grant number: 16/05311-2
• Support Opportunities: Research Projects - Thematic Grants
• Duration: February 01, 2018 - January 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Mari Cleide Sogayar
• Grantee: Mari Cleide Sogayar
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Eleazar Chaib ; Irene de Lourdes Noronha
• Associated researchers: Adriano Barreto Nogueira ; Aline Ramos Maia Lobba ; Ana Claudia Oliveira Carreira Nishiyama ; André Fujita ; Antonio Carlos Campos de Carvalho ; Carlos Deocesano-Pereira ; Christian Bowman-Colin ; Fernando Henrique Lojudice da Silva ; Fernando Janczur Velloso ; Isa Dietrich ; Jose Alexandre Marzagão Barbuto ; José Mauro Granjeiro ; Juliana de Sá da Silva ; 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
• Associated grant(s): 22/10658-2 - 9th Latin American Symposium on Cell Culture Technology - SLATCC 2022, AR.EXT
• Associated scholarship(s): 24/01156-9 - Comparative analysis of molecular and cellular mechanisms related to tumour evasion in the triple negative Hs578T breast cancer cell lineage via the PD-1/PDL-1 axis., BP.IC; 23/09475-3 - Biomaterial containing extracellular matrix for pancreatic islet microencapsulation and reversion of Diabetes induced in animals., BP.IC; 23/00684-9 - Proteolytic processing of recombinant anti-PD-1 monoclonal antibody through ectopic expression of the PACE enzyme in CHO-DG44 cells., BP.IC; + associated scholarships 22/01906-2 - Glycoengineering of CHO-DG44 cells for the production of recombinant human R-Spondin 1 (rhRSPO1) with high content of terminally sialylated N-linked glycan chains, BP.DD; 22/08841-3 - Regenerative Medicine aiming at therapy for chronic degenerative diseases (cancer and diabetes)., BP.TT; 21/07975-3 - Regenerative Medicine aiming at therapy for chronic degenerative diseases (cancer and diabetes)., BP.TT; 20/11005-7 - Research on depressive behavior development in mice with Type 1 Diabetes Mellitus, BP.IC; 20/15660-0 - Regenerative medicine aiming at therapy for chronic degenerative diseases (cancer and diabetes), BP.TT; 19/21935-4 - Characterization of embryonic stem cell transcriptome during its differentiation into insulin-producing cells in the absence and presence of growth/differentiation peptide factors, BP.DR; 20/03278-3 - Regenerative medicine aiming at therapy for chronic degenerative diseases (cancer and diabetes), BP.TT; 19/22267-5 - Influence of peptide growth/differentiation factors in the process of murine embryonic stem cells (mESCs) differentiation into insulin-producing cells (IPCs), BP.IC; 20/01141-0 - Isolation and characterization of pancreatic islets., BP.TT; 19/03893-2 - Systems biology approaches for the study of signaling pathways by RNA-seq in triple-negative breast cancer cell lines, BP.IC - associated scholarships

Abstract

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

(19)

(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. (16/05311-2)

TROMBETTA-LIMA, MARINA; ASSIS-RIBAS, THAIS; CINTRA, RICARDO C.; CAMPEIRO, JOANA D.; GUERREIRO, JULIANO R.; WINNISCHOFER, SHEILA M. B.; NASCIMENTO, ISIS C. C.; ULRICH, HENNING; HAYASHI, MIRIAN A. F.; SOGAYAR, MARI C.. Impact of Reck expression and promoter activity in neuronal in vitro differentiation. MOLECULAR BIOLOGY REPORTS, v. 48, n. 2, FEB 2021. (18/20014-0, 16/05311-2, 18/07366-4, 14/50891-1, 19/13112-8, 15/26328-8, 16/18277-7, 12/50880-4, 17/02413-1)

JACOMASSO, THIAGO; RIBAS, HENNRIQUE TABORDA; TROMBETTA-LIMA, MARINA; KONIG, MICHELLE SILBERSPITZ; TRINDADE, EDVALDO SILVA; MARTINEZ, GLAUCIA REGINA; SOGAYAR, MARI CLEIDE; WINNISCHOFER, SHEILA MARIA BROCHADO. The alternatively spliced RECK transcript variant 3 is a predictor of poor survival for melanoma patients being upregulated in aggressive cell lines and modulating MMP gene expression in vitro. Melanoma Research, v. 30, n. 3, p. 223-234, JUN 2020. (16/18277-7, 16/05311-2, 15/26328-8)

FACIOLI, ROBERTA; LOJUDICE, FERNANDO HENRIQUE; ANAUATE, ANA CAROLINA; MAQUIGUSSA, EDGAR; NISHIURA, JOSE LUIZ; HEILBERG, ITA PFEFERMAN; SOGAYAR, MARI CLEIDE; BOIM, MIRIAN APARECIDA. Kidney organoids generated from erythroid progenitors cells of patients with autosomal dominant polycystic kidney disease. PLoS One, v. 16, n. 8, 2021. (16/05311-2, 15/23345-9)

LEAL-LOPES, CAMILA; GRAZIOLI, GISELLA; MARES-GUIA, THIAGO R.; COELHO-SAMPAIO, TATIANA; SOGAYAR, MARI CLEIDE. Polymerized laminin incorporation into alginate-based microcapsules reduces pericapsular overgrowth and inflammation. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, v. 13, n. 10, AUG 2019. (16/05311-2, 13/00664-6)

LEVIN, GABRIEL; KOGA, BRUNA ANDRADE AGUIAR; BELCHIOR, GUSTAVO GROSS; CARREIRA, ANA CLAUDIA OLIVEIRA; SOGAYAR, MARI CLEIDE. Production, purification and characterization of recombinant human R-spondin1 (RSPO1) protein stably expressed in human HEK293 cells. BMC Biotechnology, v. 20, n. 1, JAN 20 2020. (17/01072-6, 15/11128-3, 16/05311-2)

KOGA, BRUNA ANDRADE AGUIAR; FERNANDES, LETICIA ALVES; FRATINI, PAULA; SOGAYAR, MARI CLEIDE; CARREIRA, ANA CLAUDIA OLIVEIRA. Role of MSC-derived small extracellular vesicles in tissue repair and regeneration. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 10, p. 16-pg., 2023-03-01. (16/05311-2)

PEREIRA, TULIO FELIPE; LEVIN, GABRIEL; DEOCESANO-PEREIRA, CARLOS; CAODAGLIO, AMANDA SCHIERSNER; FUJITA, ANDRE; TONSO, ALDO; SOGAYAR, MARI CLEIDE. Fluorescence-based method is more accurate than counting-based methods for plotting growth curves of adherent cells. BMC RESEARCH NOTES, v. 13, n. 1, p. 7-pg., 2020-02-04. (16/05311-2, 16/01626-9)

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, p. 21-pg., 2019-04-30. (16/05311-2)

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. (15/26328-8, 16/05311-2, 16/22298-0, 16/18277-7, 15/25776-7)

LEVIN, GABRIEL; ZUBER, SAMUEL M.; SQUILLARO, I, ANTHONY; SOGAYAR, MARI CLEIDE; GRIKSCHEIT, TRACY C.; CARREIRA, ANA CLAUDIA O.. R-Spondin 1 (RSPO1) Increases Mouse Intestinal Organoid Unit Size and Survivalin vitroand Improves Tissue-Engineered Small Intestine Formationin vivo. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, v. 8, JUN 5 2020. (17/01072-6, 16/05311-2)

SPINDOLA, ADAUTO; TARGA, ADRIANO D. S.; RODRIGUES, LAIS SOARES; WINNISCHOFER, SHEILA MARIA BROCHADO; LIMA, MARCELO M. S.; SOGAYAR, MARI CLEIDE; TROMBETTA-LIMA, MARINA. Increased Mmp/Reck Expression Ratio Is Associated with Increased Recognition Memory Performance in a Parkinson's Disease Animal Model. Molecular Neurobiology, v. 57, n. 2, p. 837-847, FEB 2020. (16/18277-7, 16/05311-2, 15/26328-8)

DEOCESANO-PEREIRA, CARLOS; MACHADO, RAQUEL A. C.; CHUDZINSKI-TAVASSI, ANA MARISA; SOGAYAR, MARI CLEIDE. Emerging Roles and Potential Applications of Non-Coding RNAs in Glioblastoma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 7, APR 2020. (15/50040-4, 16/05311-2)

BONATO, RAFAEL SILVA; FERNANDES, GUSTAVO VICENTIS DE OLIVEIRA; CALASANS-MAIA, MONICA DIUANA; MELLO, ALEXANDRE; ROSSI, ALEXANDRE MALTA; OLIVEIRA CARREIRA, ANA CLAUDIA; SOGAYAR, MARI CLEIDE; GRANJEIRO, JOSE MAURO. The Influence of rhBMP-7 Associated with Nanometric Hydroxyapatite Coatings Titanium Implant on the Osseointegration: A Pre-Clinical Study. POLYMERS, v. 14, n. 19, p. 11-pg., 2022-10-01. (16/05311-2)

BORGES SILVA, ISAURA BEATRIZ; KIMURA, CAMILA HARUMI; COLANTONI, VITOR PRADO; SOGAYAR, MARI CLEIDE. Stem cells differentiation into insulin-producing cells (IPCs): recent advances and current challenges. STEM CELL RESEARCH & THERAPY, v. 13, n. 1, p. 24-pg., 2022-07-15. (16/05311-2, 19/21935-4, 19/22267-5)

MASELLI, KATHRYN M.; LEVIN, GABRIEL; GEE, KRISTIN M.; LEEFLANG, ELISABETH J.; CARREIRA, ANA CLAUDIA O.; SOGAYAR, MARI CLEIDE; GRIKSCHEIT, TRACY C.. R-Spondin1 enhances wnt signaling and decreases weight loss in short bowel syndrome zebrafish. BIOCHEMISTRY AND BIOPHYSICS REPORTS, v. 25, MAR 2021. (16/05311-2, 15/11128-3, 17/01072-6)

MANTOVANI, MARLUCE DA CUNHA; GABANYI, ILANA; PANTANALI, CARLOS ANDRES; SANTOS, VINICIUS ROCHA; CORREA-GIANNELLA, MARIA LUCIA CARDILLO; SOGAYAR, MARI CLEIDE. Islet transplantation: overcoming the organ shortage. DIABETOLOGY & METABOLIC SYNDROME, v. 15, n. 1, p. 8-pg., 2023-07-01. (16/05311-2)

M.S. MORAES-ALMEIDA; M.C. SOGAYAR; M.A.A. DEMASI. Evidence of a synthetic lethality interaction between SETDB1 histone methyltransferase and CHD4 chromatin remodeling protein in a triple negative breast cancer cell line. Brazilian Journal of Medical and Biological Research, v. 56, 2023-11-13. (16/05311-2)

L. ANDREONE; A.F. DOS SANTOS; R.A.M. WAILEMANN; L.F. TERRA; V.M. GOMES; J. MACEDO DA SILVA; L. ROSA-FERNANDES; M.C. SOGAYAR; G. PALMISANO; L. LABRIOLA; et al. Cotransplantation of marginal mass allogeneic islets with 3D culture-derived adult human skin cells improves glycemia in diabetic mice. Brazilian Journal of Medical and Biological Research, v. 56, 2023-09-22. (12/50680-5, 16/05311-2, 13/07937-8, 13/07029-4, 12/16785-4)