Endochondral Ossification Induced by Cell Transplantation of Endothelial Cells and Bone Marrow Stromal Cells with Copolymer Scaffold Using a Rat Calvarial Defect Model

Abstract

It has been recently reported that, in a rat calvarial defect model, adding endothelial cells (ECs) to a culture of bone marrow stromal cells (BMSCs) significantly enhanced bone formation. The aim of this study is to further investigate the ossification process of newly formed osteoid and host response to the poly(L-lactide-co-1,5-dioxepan-2-one) [poly(LLA-co-DXO)] scaffolds based on previous research. Several different histological methods and a PCR Array were applied to evaluate newly formed osteoid after 8 weeks after implantation. Histological results showed osteoid formed in rat calvarial defects and endochondral ossification-related genes, such as dentin matrix acidic phosphoprotein 1 (Dmp1) and collagen type II, and alpha 1 (Col2a1) exhibited greater expression in the CO (implantation with BMSC/EC/Scaffold constructs) than the BMSC group (implantation with BMSC/Scaffold constructs) as demonstrated by PCR Array. It was important to notice that cartilage-like tissue formed in the pores of the copolymer scaffolds. In addition, multinucleated giant cells (MNGCs) were observed surrounding the scaffold fragments. It was concluded that the mechanism of ossification might be an endochondral ossification process when the copolymer scaffolds loaded with co-cultured ECs/BMSCs were implanted into rat calvarial defects. MNGCs were induced by the poly(LLA-co-DXO) scaffolds after implantation, and more specific in vivo studies are needed to gain a better understanding of host response to copolymer scaffolds.

Osteoconductive Properties of a Volume-Stable Collagen Matrix in Rat Calvaria Defects: A Pilot Study

“…If we relate the findings to those of others, cartilage-like tissue formed in the pores of copolymer scaffolds not containing TGF-β when transplanted into rat calvaria defects [42]. This is maybe not surprising as calvaria-derived cells are rich in mesenchymal progenitors with the capacity to differentiate into the chondrogenic lineage under the appropriate conditions [43].…”

Subchondral osteoclasts and osteoarthritis: new insights and potential therapeutic avenues

“…Endothelial cells can participate in the inflammatory response in the subchondral bone region in various ways, such as through the calcium signaling pathway, which produces several immune factors and chemokines that direct immune cells to the damaged site and promote tissue repair and regeneration [58] . Simultaneously, endothelial cells produce a variety of cytokines, such as basic fibroblast growth factor (bFGF) and ADAMTS, thereby promoting the proliferation and differentiation of BMSCs and maintaining the regenerative capacity of bone tissue [ 59 , 60 ]. Additionally, endothelial cells partially regulate the maturation and differentiation of osteoblasts.…”