EVALUATION OF THE MYOGENIC AND FIBROGENIC POTENTIAL OF THE SECRETOME FROM MESENCHYMAL STEM CELLS THROUGH THE OVEREXPRESSION OF TGF¿-1RII AND SDF-1.

• Grant number: 25/10443-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Roberta Sessa Stilhano Yamaguchi
• Grantee: Yollanda Chan Câmara
• Host Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). São Paulo , SP, Brazil

Abstract

Skeletal muscle tissue, responsible for approximately 40% of body weight, is essential for mobility and protein metabolism, but its regeneration can be compromised by fibrotic processes. These events are regulated by dynamic interactions between satellite cells (responsible for repair), extracellular matrix (ECM), and factors such as TGF-¿1, which, when dysregulated, promotes fibrosis via fibroblast activation and excessive collagen deposition. Inflammation plays a dual role in the process: M1 macrophages initiate the injury response, while M2 macrophages assist in repair; however, an imbalance in this polarization can worsen fibrosis.In this context, mesenchymal stem cells (MSCs) emerge as a promising therapeutic strategy due to their secretome - a set of bioactive factors (cytokines, exosomes, growth factors) that modulate inflammation, angiogenesis and regeneration. Studies highlight their potential to reduce fibrosis via suppression of TGF-¿1 and stimulation of ECM degradation by metalloproteinases (MMPs). Furthermore, secretome-based therapies offer advantages over cell transplants, such as lower immunogenic risk and greater ease of standardization.The expected results are: characterization of a unique secretomic profile with higher concentration of pro-regenerative factors and lower proportion of pro-fibrotic mediators; demonstration of this secretome's ability to promote myogenic differentiation while inhibiting fibroblast activation; and evidence that combined overexpression of sTGF-¿1 and SDF-1 enhances the therapeutic effects of MSCs. This approach may offer an effective alternative to conventional cell therapies, with advantages such as lower risk of fibrosis formation.