Endothelial progenitors enhanced the osteogenic capacities of mesenchymal stem cells in vitro and in a rat alveolar bone defect model

Abstract

Objective: Transplantation of mesenchymal stem cells (MSCs) may promote bone healing. Endothelial progenitor cells (EPCs) may enhance the osteogenic properties of MSCs by improving their microenvironment. We aimed to investigate whether EPCs can enhance the osteogenic properties of MSCs in vitro, and whether transplantation of EPC-MSC cell sheets could promote bone regeneration in a rat model of alveolar bone defect.

Design: MSCs and EPCs were obtained from 2-week-old Sprague-Dawley rats. Cell sheets were prepared using MSCs and MSCs co-cultured with EPCs. Morphological characteristics of cell sheets were observed by H&E staining. Osteogenic differentiation capacities of the cell sheets were assessed by alkaline phosphatase (ALP) staining, Alizarin Red S staining and qRT-PCR. Cell sheets were transplanted into alveolar bone defects in 8-week-old rats. Six weeks later, bone formation was assessed by micro-CT.

Results: EPC-MSC sheets exhibited faster osteogenesis than MSC sheets. Six weeks after implantation, alveolar bone defects transplanted with EPC-MSC sheets exhibited a better bone reconstruction. MSC sheets generated new bone that partially covered the defect areas, while EPC-MSC sheets exhibited more robust osteogenic activity, with continuous new bone that almost covered the entire defect area.

Conclusions: Transplantation of cell sheets containing EPCs and MSCs promoted bone regeneration.

Keywords: Bone regeneration; Cell sheets; Cell transplantation; Early vascularization; Endothelial progenitor cells; Mesenchymal stem cells.