Role of GM-CSF in the repair of muscule injury: gene therapy for muscle injuries

• Grant number: 11/00859-6
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2011
• End date: October 31, 2013
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Sang Won Han
• Grantee: Sang Won Han
• Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Valderez Bastos Valero-Lapchik

Abstract

Muscle injury is one that occurs most often among athletes and is the main reason for the abandonment of their activities. Repair of the damaged muscle tissue is a slow process and often incomplete due to exacerbated fibrosis. For tissue repair needs of angiogenesis (also arteriogenesis and vasculogenesis), myogenesis and fibrogenesis in sync, and these processes are regulated by several growth and angiogenic factors. GM-CSF is a hematopoietic factor responsible for proliferation and differentiation of myeloblasts and monoblasts. Recently, our group and others have demonstrated that this factor promotes remodeling and formation of blood vessels in animal ischemic limbs leading to almost full recovery of these limbs. Besides these effects, we also observed an increase in muscle mass and strength, and drastic reduction of fibrosis, which are necessary consequences for a good muscle repair. From these observations, we propose a hypothesis that GM-CSF may act as a master factor in the repair process of damaged muscle tissue, where this factor should regulate directly or indirectly the factors responsible for angiogenesis, myogenesis and fibrogenesis. The main objective of this project is to validate this hypothesis through in vivo experiments with mice with injured muscles and in vitro with cells that make up the skeletal muscle tissue. After these studies, the project should end with the establishment of a protocol for gene therapy for muscle injuries with GM-CSF. (AU)

Scientific publications

(5)

(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)

CUNHA, FLAVIA FRANCO; MARTINS, LEONARDO; MATSUMOTO MARTIN, PRISCILA KEIKO; STILHANO, ROBERTA SESSA; HAN, SANG WON. A comparison of the reparative and angiogenic properties of mesenchymal stem cells derived from the bone marrow of BALB/c and C57/BL6 mice in a model of limb ischemia. STEM CELL RESEARCH & THERAPY, v. 4, JUL 26 2013. (11/00859-6)

MCNEILL INGHAM, SHEILA JEAN; POCHINI, ALBERTO DE CASTRO; DE OLIVEIRA, DANIEL ANTONIO; GARCIA LISBOA, BIANCA CRISTINA; BEUTEL, ABRAM; VALERO-LAPCHIK, VALDEREZ BASTOS; FERREIRA, ANA MARIA; ABDALLA, RENE JORGE; COHEN, MOISES; HAN, SANG WON. Bupivacaine Injection Leads to Muscle Force Reduction and Histologic Changes in a Murine Model. PM&R, v. 3, n. 12, p. 1106-1109, DEC 2011. (11/00859-6)

DA CUNHA, FLAVIA FRANCO; MARTINS, LEONARDO; MATSUMOTO MARTIN, PRISCILA KEIKO; STILHANO, ROBERTA SESSA; PAREDES GAMERO, EDGAR JULIAN; HAN, SANG WON. Comparison of treatments of peripheral arterial disease with mesenchymal stromal cells and mesenchymal stromal cells modified with granulocyte and macrophage colony-stimulating factor. CYTOTHERAPY, v. 15, n. 7, p. 820-829, JUL 2013. (11/00859-6)

YASUMURA, EDUARDO GALLATTI; STILHANO, ROBERTA SESSA; SAMOTO, VIVIAN YOCHIKO; MATSUMOTO, PRISCILA KEIKO; DE CARVALHO, LEONARDO PINTO; VALERO LAPCHIK, VALDEREZ BASTOS; HAN, SANG WON. Treatment of Mouse Limb Ischemia with an Integrative Hypoxia-Responsive Vector Expressing the Vascular Endothelial Growth Factor Gene. PLoS One, v. 7, n. 3, p. e33944, 2012. (11/00859-6)

ROSEGUINI, BRUNO T.; SILVA, LEONARDO M.; POLOTOW, TATIANA G.; BARROS, MARCELO P.; SOUCCAR, CADEN; HAN, SANG W.. Effects of N-acetylcysteine on skeletal muscle structure and function in a mouse model of peripheral arterial insufficiency. JOURNAL OF VASCULAR SURGERY, v. 61, n. 3, p. 777-786, MAR 2015. (11/00859-6, 10/51344-3, 11/18197-0)