The co-culture of ASCs and EPCs promotes vascularized bone regeneration in critical-sized bone defects of cranial bone in rats

Yuanjia He,Qiang Ao,Shuang Lin,Xiaoning He

doi:10.1186/s13287-020-01858-6

Abstract

BackgroundThe repair of critical-sized bone defect represents a challenging problem in bone tissue engineering. To address the most important problem in bone defect repair, namely insufficient blood supply, this study aimed to find a method that can promote the formation of vascularized bone tissue.MethodThe phenotypes of ASCs and EPCs were identified respectively, and ASCs/EPCs were co-cultured in vitro to detect the expression of osteogenic and angiogenic genes. Furthermore, the co-culture system combined with scaffold material was used to repair the critical-sized bone defects of the cranial bone in rats.ResultsThe co-culture of ASCs/EPCs could increase osteogenesis and angiogenesis-related gene expression in vitro. The results of in vivo animal experiments demonstrated that the ASC/EPC group could promote bone regeneration and vascularization in the meantime and then significantly accelerate the repair of critical-sized bone defects.ConclusionIt is feasible to replace traditional single seed cells with ASC/EPC co-culture system for vascularized bone regeneration. This system could ultimately enable clinicians to better repair the defect of craniofacial bone and avoid donor site morbidity.

Highlights

The repair of critical-sized bone defect represents a challenging problem in bone tissue engineering
The results of in vivo animal experiments demonstrated that the Adipose-derived mesenchymal stem cells (ASCs)/endothelial progenitor cells (EPCs) group could promote bone regeneration and vascularization in the meantime and significantly accelerate the repair of critical-sized bone defects
By quantifying the blood vessel density (BVD) of the entire implant area, it was confirmed that the BVD of the ASC/EPC group was significantly higher than that of the other groups (Fig. 6e). These results demonstrated that EPCs could promote vascular growth and that the co-culture of ASCs and EPCs dramatically enhances vascularized bone regeneration

Summary

Introduction

The repair of critical-sized bone defect represents a challenging problem in bone tissue engineering. It is mainly due to the lack of angiogenesis in the implanted tissue-engineered bone, inability to obtain sufficient nutrition, reducing the amount of regenerated He et al Stem Cell Research & Therapy (2020) 11:338 on the vascular system around the defect area, which can continuously recruit nearby bone progenitor cells for osteogenic repair and provide nutritional support for the repair process. Endothelial progenitor cells (EPCs) are precursor cells of vascular endothelial cells, which have the ability to proliferate, migrate, and differentiate into cells arranged along the lumen of blood vessels [14] It has been found in previous studies that EPCs can enhance the osteogenic activity of pre-osteoblasts [15] and play an important role in bone formation and repair [16, 17]. The co-culture of ADSCs and EPCs may promote the formation of new bone and blood vessels through cell-cell interactions

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