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Effect of local injection of mesenchymal stem cells combined with systemic injections of parathyroid hormone and pentoxifylline on bone repair

Grant number: 20/03616-6
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2020
Effective date (End): February 29, 2024
Field of knowledge:Health Sciences - Dentistry - Oral and Maxillofacial Surgery
Principal researcher:Adalberto Luiz Rosa
Grantee:Jaqueline Isadora Reis Ramos
Home 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

Bone tissue shows great regeneration capacity when injured by trauma, inflammation or neoplasms. However, in many situations the damage exceeds its regeneration capacity. For these cases, some additional treatments are needed, including pharmacological therapy based on anabolic drugs to bone tissue and cell therapy based on local cell injections. For pharmacological therapy, two clinically available drugs have anabolic effect on bone tissue: Parathyroid Hormone (PTH) and pentoxifylline (PTX), both being able to increase bone formation. For cell therapy, a variety of cells either undifferentiated, such as Mesenchymal Stem Cells (MSCs) or differentiated, such as osteoblasts, may be used. These cells share similar high potential of bone induction when locally injected into defects, although they are not able to bone regeneration. In keeping with this, the aim of this study is to evaluate the effect of combining local injection of bone marrow MSCs with systemic administration of PTH and PTX on bone repair. For this, 5 mm-defects will be made in rat calvaria and to mimic preexistent defects the treatments will begin only after two weeks of defect creation. Firstly, the dose-dependent effect of PTH and PTX on bone repair will be evaluated in order to select the most effective dose of both, then the efficacy of the combination of PTH and PTX will be evaluated. Based on these results the effect of combining local injection of MSCs with systemic injections of PTH, PTX and PTH+PTX on bone repair will be evaluated. Our hypothesis is that the combination of MSCs with PTH+PTX will be able to induce the full regeneration of rat calvaria defects. (AU)

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