Therapeutic potential evaluation of soluble factors released by mesenchymal stem cells on progressive muscular dystrophies

• Grant number: 12/50199-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2012
• End date: September 30, 2014
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mayana Zatz
• Grantee: Mariane Secco
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Progressive Muscular Dystrophies (PMDs) are a group of genetic diseases characterized by progressive and irreversible degeneration of skeletal muscles. Mesenchymal stem cells (MSCs) are among the latest therapeutic strategies currently under investigation for PMDs. However, the variables responsible for the successful transplantation of MSCs have not been established yet and the results obtained are somewhat controversial. The first hypothesis studied to justify the beneficial effects of cell therapy is myogenic differentiation of MSCs and the restore of the protein expression in the dystrophic muscle. Another hypothesis to explain the therapeutic effects of MSCs in experimental models is the indirect effect as a result of the secretion of cytokines and growth factors with anti-apoptotic, anti-fibrogenic and anti-inflammatory effects, which contribute to alleviate the dystrophic muscle symptoms. In order to investigate whether soluble factors released by MSCs can promote improved muscle function, we will proceed with the administration of the conditioned medium from MSCs in animal models for muscular dystrophy. Since understanding the action mechanisms involved in the therapeutic effects promoted by MSCs is essential to optimize the clinical benefits of cell therapy, the results obtained here will be of extreme importance and may represent an important step for the start of clinical trials in patients. (AU)