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Effect of conditioned medium by mesenchymal stem cells overexpressing bone morphogenetic protein 9 on osteoblast differentiation and bone regeneration

Grant number: 20/06599-5
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): February 01, 2021
Effective date (End): July 27, 2023
Field of knowledge:Health Sciences - Dentistry - Oral and Maxillofacial Surgery
Principal Investigator:Márcio Mateus Beloti
Grantee:Robson Diego Calixto
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
Associated scholarship(s):22/00168-8 - Reprogramming of differentiated somatic cells in pluripotent cells induced (iPS) as a regenerative medicine tool, BE.EP.MS


Cell therapy approaches using bone marrow-derived mesenchymal stem cells (MSCs) have been investigated in the field of Dentistry and Medicine as a promising alternative to treat bone defects. Bone morphogenetic proteins (BMPs) are cytokines of the transforming growth factor beta (TGF-a) family and are involved in several biological processes, including osteoblastic differentiation and osteogenesis. Among the several BMPs, BMP-9 is considered one of the most osteogenic. Preliminary data of our research group have shown that MSCs overexpressing BMP-9 (MSCsBMP-9) injected into rat calvarial defects increase bone formation compared to MSCs without BMP-9 overexpression. These results may be explained, at least in part, by the fact that MSCsBMP-9 secrete bioactive molecules, which are accumulated in the culture medium when these cells are cultivated, that exert beneficial effects in the cells of the region of interest. In this context, the aims of this study are: (1) to characterize the conditioned media from MSCsBMP-9 regarding the presence of cytokines, growth factors and proteases, (2) to evaluate the effect of MSCsBMP-9 conditioned medium on migration, proliferation and osteoblastic differentiation of mouse bone marrow-derived MSCs and (3) to evaluate the effect of MSCsBMP-9 conditioned medium on bone regeneration of mouse calvarial defects. Quantitative data will be subjected to the normal curve adherence test to determine the appropriate statistical test to be applied, and the level of significance will be set at 5%. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CALIXTO, ROBSON DIEGO; FREITAS, GILEADE PEREIRA; SOUZA, PAOLA GOMES; RAMOS, JAQUELINE ISADORA REIS; SANTOS, ISABELA CRISTINE; DE OLIVEIRA, FABIOLA SINGARETTI; ALMEIDA, ADRIANA LUISA GONCALVES; ROSA, ADALBERTO LUIZ; BELOTI, MARCIO MATEUS. Effect of the secretome of mesenchymal stem cells overexpressing BMP-9 on osteoblast differentiation and bone repair. Journal of Cellular Physiology, v. N/A, p. 13-pg., . (17/12622-7, 20/06599-5, 19/01346-4)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CALIXTO, Robson Diego. Effect of the secretome present in the conditioned medium of mesenchymal stem cells overexpressing BMP-9 on osteoblast differentiation and bone rapair of mouse calvarial defects. 2023. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Odontologia de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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