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To investigate how FGF2 and latent TGFbeta controls the migration and differentiation of mesenchymal stem cells at the site of cartilage injury

Grant number: 18/23457-0
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): April 01, 2019
Effective date (End): March 31, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Mario Ferretti Filho
Grantee:Felipe Bruno Dias de Oliveira
Supervisor abroad: Antonia Vincent
Home Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil
Local de pesquisa : University of Oxford, England  
Associated to the scholarship:15/14444-3 - Local and sistemicaly administrated mesenchymal cells regenerative capacity on osteoartrhitis animal model, BP.DR

Abstract

Tonia Vincent's group has previously shown that the cartilage matrix releases sequestered growth factors, including FGF2 and latent TGFbeta, in response to mechanical injury. Latent TGFbeta requires the cell surface receptor, betaglycan, also known as TGFbetaR3 in order to become activated. Repair of the cartilage in vivo is dependent on FGF2 as mice deficient in this growth factor are unable to fill a cartilage defect compared with a control strain of mouse. Whilst examining the effect of FGF2 on mesenchymal stem cell (MSC) behavior in vitro her group found that FGF2 dramatically increased mobility of MSCs in the monolayer scratch assay but inhibited differentiation to the chondrocyte lineage in a 21 day chondrogenesis assay. The hypothesis that we would like to test is that FGF2 released upon articular cartilage injury primes MSCs for subsequent activation of latent TGFbeta by regulation of TGFbetaR3.