Effect of the secretome of mesenchymal stem cells overexpressing BMP-9 on osteoblast differentiation and bone repair

Author(s)

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

• Document type: Journal article
• Source: Journal of Cellular Physiology; v. N/A, p. 13-pg., 2023-09-03.

Abstract

The secretome present in the conditioned medium (CM) of mesenchymal stem cells (MSCs) is a promising tool to be used in therapies to promote bone regeneration. Considering the high osteogenic potential of the bone morphogenetic protein 9 (BMP-9), we hypothesized that the secretome of MSCs overexpressing BMP-9 (MSCsBMP-9) enhances the osteoblast differentiation of MSCs and the bone formation in calvarial defects. CM of either MSCsBMP-9 (CM-MSCsBMP-9) or MSCs without BMP-9 overexpression (CM-MSCsVPR) were obtained at different periods. As the CM-MSCsBMP-9 generated after 1 h presented the highest BMP-9 concentration, CM-MSCsBMP-9 and CM-MSCsVPR were collected at this time point and used to culture MSCs and to be injected into mouse calvarial defects. The CM-MSCsBMP-9 enhanced the osteoblast differentiation of MSC by upregulating RUNX2, alkaline phosphatase (ALP) and osteopontin protein expression, and ALP activity, compared with CM-MSCsVPR. The CM-MSCsBMP-9 also enhanced the bone repair of mouse calvarial defects, increasing bone volume, bone volume/total volume, bone surface, and trabecular number compared with untreated defects and defects treated with CM-MSCsVPR or even with MSCsBMP-9 themselves. In conclusion, the potential of the MSCBMP-9-secretome to induce osteoblast differentiation and bone formation shed lights on novel cell-free-based therapies to promote bone regeneration of challenging defects. (AU)

• FAPESP's process: 17/12622-7 - Cell therapy: potential of mesenchymal stem cells, VEGF-A and BMP-9 to regenerate bone tissue
• Grantee: Adalberto Luiz Rosa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/06599-5 - Effect of conditioned medium by mesenchymal stem cells overexpressing bone morphogenetic protein 9 on osteoblast differentiation and bone regeneration
• Grantee: Robson Diego Calixto
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/01346-4 - Evaluation of the angiogenic and bone regeneration potentials of BM-MSCs and AT-BMCs genetically edited by CRISP-Cas9 to overexpress VEGF-A and BMP-9
• Grantee: Gileade Pereira Freitas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral