The role of tissue niche in muscle regeneration and homeostasis

• Grant number: 12/21659-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 01, 2013
• End date: February 28, 2013
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Maeli Dal Pai
• Grantee: Raquel Santilone Bertaglia de Almeida
• Supervisor: Antonio Musarò
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: Università degli Studi di Roma La Sapienza, Italy
• Associated to the scholarship: 11/08603-0 - Expression of microRNAs and myogenic factors in skeletal muscle of rats submitted to atrophy and physical training, BP.DR

Abstract

Muscular dystrophies are a group of diseases that primarily affect skeletal muscle and are characterized by progressive muscle wasting and weakness. One the most important form is Duchenne Muscular Dystrophy (DMD) caused by a mutation in the gene encoding the protein dystrophin, resulting in loss of sarcolemma integrity of muscle fiber. In an attempt to restore dystrophin in the muscle fiber sarcolemma, several treatments have been studied, including the use of stem cell. Furthermore, preliminary evidence demonstrates that Insulin-like Growth Factor-1 (mIGF-1) sustains muscle hypertophy and skeletal muscle regeneration, enhances the recruitment of circulating stem cells in injured muscle and counteracts muscle wasting in mdx dystrophic mice, reducing the inflammatory response and improving muscle mass and strength and elevating pathways associated with muscle survival and regeneration.Thus, a combination of therapies to improve muscle regeneration capacity and to prevent necrosis of the muscle tissue can be an effective treatment to reduce the symptoms caused by DMD. The hypothesis of our study is that modifying the satellite cell niche in DMD, by overexpression of muscle IGF-1, can improve the effectiveness of therapy mediated by such cells. The objective of this study are to approaches of stem cell therapy to counteract muscle decline associated with Duchene Muscular Dystrophy; to verify whether combinated therapeutic approach (transplanted mdx and mdx/mIGF-1) ensures the long-term phenotype recovered , defining the role of mIGF-1 and other factors involved in regeneration and homeostasis of injured muscles at different stages of the disease. To thus be used mdx/mIGF-1 mdx mice and aged 3 and 18 months graft undergoing stem cell isolated from bone marrow. After treatment, the animals are sacrificed and the diaphragm and EDL muscles removed for analysis of morphological, functional and molecular. (AU)