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

Abstract

Background: The 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. Method: The 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. Results: The 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. Conclusion: It 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.

Cross-Talk Between Mesenchymal Stromal Cells (MSCs) and Endothelial Progenitor Cells (EPCs) in Bone Regeneration

“…The AT-MSC/BM-EPC combination increases osteogenesis and angiogenesis-related gene expression in vitro. The results of animal experiments demonstrated that the AT-MSC/BM-EPC association accelerates critical-sized bone defect repair (He et al, 2020). Coculture of AT-MSC sheet-BM-EPCs generated more bone and cartilage.…”

A Narrative Review of Cell-Based Approaches for Cranial Bone Regeneration

“…To this end, both cell types were co-cultured in vitro prior to co-implantation. Encouraging results, in terms of enhanced bone healing compared with implantation of osteogenic MSCs only, were obtained by combining co-cultured endothelial progenitor cells with bone marrow-or adipose-derived MSCs in HA-based scaffolds [87,88]. Interestingly, Xu et al [89] demonstrated that repair of critical size calvarial defects in rats can be promoted using osteogenic and endothelial cell sheets differentiated in vitro from bone marrow-derived MSCs, without the need for any scaffold providing structural support.…”

Use of stem cells in bone regeneration in cleft palate patients: review and recommendations

“…Another method that has been evaluated for enhancing osteogenesis and neovascularization of augmented stem cells is co-culturing and co-transplantation of two different types of stem cells. Co-culturing and co-transplantation of ADSCs and endothelial progenitor cells (EPCs) has promoted bone regeneration and angiogenesis in a rat cranial defect 61 . In a study by Wu et al 62 , the addition of epithelial progenitor cells to BMMSCs has resulted in the upregulation of mRNA expressions of VEGF, osteonectin, osteopontin, and collagen type 1 and an increase in alkaline phosphatase activity and CD34.…”