Gene and cell therapy via alginate microgels for muscle injuries

• Grant number: 19/10922-9
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: October 01, 2020 - September 30, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Roberta Sessa Stilhano Yamaguchi
• Grantee: Roberta Sessa Stilhano Yamaguchi
• Host Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil
• Associated researchers: Ariadiny de Lima Caetano ; Eduardo Alexandre Barros e Silva ; Gustavo José da Silva Pereira ; Ricardo Jorge Espanhol Andrade
• Associated grant(s): 21/00168-5 - Multi-user equipamento approved in grants 201//10922-9: QuantStudio" 5 Real-Time PCR System, AP.EMU
• Associated scholarship(s): 24/00290-3 - Muscle Repair in Focus: A Scientific Dissemination Project on Gene and Cell Therapy for the Treatment of Muscle Injuries, BP.JC; 24/00298-4 - Muscle Repair in Focus: A Scientific Dissemination Project on Gene and Cell Therapy for the Treatment of Muscle Injuries, BP.JC; 22/12769-6 - Alginate hydrogel encapsulated MDSC cell spheroids delivery as a regenerative therapy to muscle injury in vivo, BP.IC; 21/02446-2 - Vectors engineering expressing TGFb1 type II soluble receptor under control of NF-kB promoter and expression analysis in 2D and 3D muscle cultures, BP.MS; 21/02645-5 - Cell therapy with murine muscle derived stem cells encapsulated by alginate microgels for muscle injuries treatment, BP.MS

Abstract

Injuries and diseases of the musculoskeletal system are extremely common and account for over 6 million visits to emergency departments each year. After injury, muscle tissue needs to be repaired and allowed to regenerate. During this process, the formation of fibrous tissue makes adequate muscle contraction extremely difficult, and can lead to muscle contractures and chronic pain. Gene (GT) and cellular therapies associated with biomaterials such as alginate hydrogels emerge as innovative forms of treatment to reduce fibrosis. However, they are unable to act only when tissue regeneration is necessary. In this sense, it is suggested that modulation of the main cytokine involved during the fibrosis process, TGFb1, via GT and cell therapy may confer great clinical relevance in cases of tissue regeneration. Therefore, this project has two major parts. The first part investigates a GT procedure for muscle regeneration based on the modulation of TGFb1 level. For this, a lentivector (Lv) will be constructed that will express the soluble TGFb1 type II receptor (sTbRII) under the control of the NF-kB-inducible promoter. The Lv will be encapsulated in alginate microgels, which will serve as carriers to obtain a controlled release of the vectors in target tissue. The second part of the project will involve cell therapy with muscle-derived stem cell-like cells (MDSCs) and injury induced muscle-derived stem cell-like cells (iMDSCs), which have a high capacity for differentiation, including the formation of blood vessels. MDSCs and iMDSCs will be encapsulated in alginate microgels to create a therapeutic flap, containing stem cells and endothelial cells for the treatment of muscle damage in a murine model in vivo. These results are expected to reduce muscle fibrosis, increase tissue regeneration, and promote functional recovery of skeletal muscle. (AU)

Scientific publications

(4)

(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)

COSTA, ANGELICA JARDIM; LEMES, ROBERTHA MARIANA RODRIGUES; BARTOLOMEO, CYNTHIA SILVA; NUNES, TAMIRES ALVES; PEREIRA, GABRIELA CRUZ; OLIVEIRA, RAFAELA BRITO; GOMES, ALEXANDRE LOPES; SMAILI, SORAYA SOUBHI; MACIEL, RUI MONTEIRO DE BARROS; NEWSON, LOUISE; et al. Overexpression of estrogen receptor GPER1 and G1 treatment reduces SARS-CoV-2 infection in BEAS-2B bronchial cells. Molecular and Cellular Endocrinology, v. 558, p. 8-pg., 2022-12-01. (20/04709-8, 06/60402-1, 18/06088-0, 20/13480-4, 20/06153-7, 18/02762-9, 16/20796-2, 19/10922-9)

RODRIGUES LEMES, ROBERTHA MARIANA; COSTA, ANGELICA JARDIM; BARTOLOMEO, CYNTHIA SILVA; BASSANI, TAYSA BERVIAN; NISHINO, MICHELLE SAYURI; DA SILVA PEREIRA, GUSTAVO JOSE; SMAILI, SORAYA SOUBHI; DE BARROS MACIEL, RUI MONTEIRO; BRACONI, CARLA TORRES; DA CRUZ, EDGAR FERREIRA; et al. 17 beta-estradiol reduces SARS-CoV-2 infection in vitro. PHYSIOLOGICAL REPORTS, v. 9, n. 2, JAN 2021. (16/20796-2, 06/60402-1, 18/06088-0, 20/06153-7, 19/10922-9, 20/04709-8)

BARTOLOMEO, CYNTHIA SILVA; LEMES, ROBERTHA MARIANA RODRIGUES; MORAIS, RAFAEL LEITE; PERERIA, GABRIELA CRUZ; NUNES, TAMIRES ALVES; COSTA, ANGELICA JARDIM; MACIEL, RUI MONTEIRO DE BARROS; BRACONI, CARLA TORRES; MARICATO, JULIANA TERZI; JANINI, LUIZ MARIO RAMOS; et al. SARS-CoV-2 infection and replication kinetics in different human cell types: The role of autophagy, cellular metabolism and ACE2 expression. Life Sciences, v. 308, p. 13-pg., 2022-09-07. (20/04709-8, 06/60402-1, 20/06153-7, 20/13480-4, 20/08943-5, 16/20796-2, 19/10922-9)

SEIXAS, MARIA LUIZA G. A.; MITRE, LUCAS PARI; SHAMS, SHAHIN; LANZUOLO, GABRIEL BARBUGIAN; BARTOLOMEO, CYNTHIA SILVA; SILVA, EDUARDO A.; PRADO, CARLA MAXIMO; URESHINO, RODRIGO; STILHANO, ROBERTA SESSA. Unraveling Muscle Impairment Associated With COVID-19 and the Role of 3D Culture in Its Investigation. FRONTIERS IN NUTRITION, v. 9, p. 20-pg., 2022-02-10. (20/04709-8, 18/06088-0, 16/20796-2, 19/10922-9)