Interactions between periosteal cells and muscle-derived blood vessels are essential for bone autograft healing
(2012) 34th Annual Meeting of the American Society for Bone and Mineral Research — Location: Minneapolis, USA (12.October.2012)
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- Abstract
- Despite major drawbacks, autologous bone transplantation remains the therapy of choice to treat large bone defects. Cell-based bone tissue engineering seems a promising alternative, but one of the key challenges is the timely formation of blood vessels to promote survival of the cells in the implant. To gain more insight in this critical process, we examined how periosteal cells orchestrate blood vessel formation during bone autograft healing. Using a murine segmental bone defect model, we confirmed the importance of periosteal cells in bone healing by showing that removal of the periosteum reduced the healing of autografts to the level of devitalized allografts. Implantation of autografts derived from GFP-mice further revealed that the donor periosteal cells were the main source of chondrocytes and osteoblasts in the callus. In vitro analysis of murine periosteum-derived cells (mPDC) indicated that they may contribute to healing not only by differentiating to osteoblasts and chondrocytes, but also by promoting endothelial cell (EC) proliferation and survival through the production of angiogenic factors such as VEGF. Ectopic co-implantation of mPDC and EC in mice proved that periosteal cells can enhance both angiogenesis and vasculogenesis in vivo. The role of periosteal cells in blood vessel formation during bone repair was further shown by the observation that autografts were surrounded by a significantly higher number of blood vessels compared to allografts. In contrast to the bone-forming cells, the blood vessel network in the autograft callus was derived almost entirely from the host and was at numerous sites connected to the vessels of the adjacent muscle. The importance of the muscle vascular bed was confirmed by insertion of a membrane in between the graft and the muscle, which completely abrogated the periosteal reaction. While an angiogenic response from the host was still observed, the blood vessels could not reach the periosteum, preventing cell proliferation and callus formation. In conclusion, our results demonstrate that periosteal cells may provide an ideal cell source for bone regeneration, not only because of their strong osteogenic and chondrogenic potential, but also by their pro-angiogenic features. In addition, we show that during bone healing the survival and function of periosteal cells drastically relies on timely interactions with blood vessels from the nearby muscle, which emphasizes the importance of the local environment.
- Affiliations
KU Leuven Laboratory of Clinical and Experimental Endocrinology KU Leuven Prometheus, Division of Skeletal Tissue Engineering
Citations
van Gastel, N., Depypere, M., Moermans, K., Stockmans, I., Schrooten, J., Maes, F., Luyten, F. P., & Carmeliet, G. (2012). Interactions between periosteal cells and muscle-derived blood vessels are essential for bone autograft healing. 34th Annual Meeting of the American Society for Bone and Mineral Research, Minneapolis, USA. https://hdl.handle.net/2078.5/109467