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Cell therapy: evaluation of the effect of mesenchymal stem cells to regenerate bone tissue of rats with Osteoporosis, Diabetes Mellitus or Arterial Hypertension

Grant number: 18/13290-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2019
Status:Discontinued
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Adalberto Luiz Rosa
Grantee:Alann Thaffarell Portilho de Souza
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
Associated scholarship(s):19/08048-9 - Effect of Ggps1 mutation on in vitro bone cell functions and in vivo diaphyseal fragility using ovariectomized mice exposed to long term nitrogen-containing bisphosphonates, BE.EP.DR

Abstract

After being injured, bone exhibits great regenerative abilities, however, systemic diseases such as Osteoporosis, Diabetes Mellitus and Arterial Hypertension, may compromise its regeneration. A promising alternative treatment is cell therapy based on the use of Mesenchymal Stem Cells (MSCs). However, several aspects need to be investigated to make this therapy an effective treatment for bone regeneration on these situations. In this context, the aims of this study are to: 1) evaluate in vitro the influence of MSCs from healthy rats (SD-MSCs) on osteoblast differentiation of MSCs from osteoporotic (ORX-MSCs), diabetic (DM-MSCs) or hypertensive (HA-MSCs) rats, using an indirect co-culture model; 2) evaluate in vitro the influence of ORX-MSCs, DM-MSCs or HA-MSCs on osteoblast differentiation of SD-MSCs, using an indirect co-culture model; 3) investigate the participation of the signaling pathways of Bone Morphogenetic Proteins (BMPs), Wnt and Integrins (ITGs) in the interactions between SD-MSCs and ORX-MSCs, DM-MSCs or HA-MSCs, grown under osteogenic conditions, in an indirect co-culture model, by silencing (shRNA) previously selected genes of these pathways and 4) evaluate in vivo the effect of MSCs from healthy rats to regenerate bone tissue of rats with Osteoporosis, Diabetes Mellitus or Arterial Hypertension. The MSCs will be isolated from the bone marrow for evaluating: cell proliferation, alkaline phosphatase (ALP) activity, extracellular matrix mineralization formation and gene expression of beta-catenin and the osteoblast markers runt related transcription factor 2 (RUNX2), osterix, ALP, bone sialoprotein and osteocalcin. Furthermore, rat calvaria defects will be created and after 2 weeks they will be injected with MSCs or vehicle (PBS-control). Four weeks post-injection bone formation will be evaluated by micro computed tomography and histological analysis. The data will be submitted to the test of adherence to the normal curve to determine the appropriate statistical analisys. The results of this study may contribute to establish the characteristics of candidate cells to be used in cell therapy in patients with Osteoporosis, Diabetes Mellitus or Arterial Hypertension. (AU)