Effect of the secretome from mesenchymal stem cells overexpressing vascular endothelial growth factor A on bone repair

• Grant number: 23/06099-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: July 31, 2024
• Field of knowledge: Health Sciences - Dentistry - Oral and Maxillofacial Surgery
• Principal Investigator: Adalberto Luiz Rosa
• Grantee: Vinícius Ardenghi Cabral
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/12622-7 - Cell therapy: potential of mesenchymal stem cells, VEGF-A and BMP-9 to regenerate bone tissue, AP.TEM

Abstract

Cell therapy using mesenchymal stem cells (MSCs) derived from adipose tissue has been the focus of scientific investigations in the fields of Dentistry and Medicine as a promising alternative to treat bone defects. Adipose tissue-derived MSCs injected in rat calvarial defects favor bone formation, at least in part, through their secretome, which regulates the osteogeneses process. Gene-edited MSCs to overexpress the vascular endothelial growth factor A (VEGFA) should produce a secretome that, among other proteins, produce higher amount of VEFGA that acts on angiogenesis with direct effects on bone repair. In this context, we hypothesized that the secretome from adipose tissue-derived MSCs overexpressing VEGFA locally injected into rat calvarial defects induces bone repair. To test this hypothesis, conditioned media that contain the secretome of MSCs genetically edited with empty vector (MSCsVPR) or to overexpress VEGFA (MSCsVEGFA) will be produced and collected. Defects with 5 mm diameter will be created in rat calvarial grouped (n = 12 per group) according to the following treatments made with injection of: (1) non-conditioned medium (NCM), (2) conditioned medium by MSCsVPR (VPR-CM) and (3) conditioned medium by MSCsVEGFA (VEGFA-CM). The formed bone tissue will be analyzed by microcomputed tomography and histological sections, and the quantitative data will be submitted to the normal distribution test to determine the appropriate statistical test to be applied.