Effect of mesenchymal stem cell-derived extracellular vesicles on osteoblastic differentiation and bone repair

• Grant number: 24/22479-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2025
• End date: April 30, 2029
• Field of knowledge: Health Sciences - Dentistry - Oral and Maxillofacial Surgery
• Principal Investigator: Adalberto Luiz Rosa
• Grantee: Elisa Borges Taveira
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/08568-2 - Investigation of the extracellular vesicles (VEs) role in the initiation, propagation, regeneration, and modeling of biological mineralization, AP.TEM

Abstract

Extracellular vesicles (EVs) participate in complex intercellular communication mechanisms relevant to the field of Regenerative Medicine, particularly in cellular therapies utilizing mesenchymal stem cells (MSCs), as these cells can generate and release EVs into the extracellular environment. This investigation aims to examine the hypothesis that MSC-derived EVs in combination with MSCs enhance bone regeneration in rat calvaria defects and promote osteoblast differentiation of MSCs and osteoblasts, the cells responsible for bone regeneration, through modulation of the signaling pathways of bone morphogenetic proteins (BMPs), Wnts, and integrins. MSC-derived EVs will be isolated via ultracentrifugation and characterized based on size, morphology, and expression of EV marker proteins. Furthermore, the capacity of MSCs and osteoblasts to internalize EVs, as well as their effects on osteoblast differentiation of MSCs and osteoblasts will be assessed through the gene expression of bone markers and alkaline phosphatase activity. The involvement of BMP, Wnts, and integrin pathways will be evaluated through expression analysis of a panel of genes, followed by silencing of select genes. The efficacy of therapy with local injection of MSCs combined with EVs on bone formation in rat calvarial defects will be determined through microtomography and histological analyses. (AU)