Project R-7235

Targeting the endothelial cell metabolism to induce angiogenesis and pulp regeneration (Research)

Despite today's technological advancements and professional health care, tooth loss remains a major public health issue in the Western world. The main cause of tooth loss is damage and necrosis of the dental pulp. As current endodontic procedures do not yield satisfactory results, there is an urgent need for new therapies. Especially development of new blood vessels (i.e. angiogenesis) represents a huge hurdle in pulp regeneration. Within the human tooth, dental pulp stem cells (DPSCs) can be found. These cells differentiate into odontoblasts and thus represent an ideal source for dental tissue engineering. While angiogenic strategies traditionally focus on growth factors, new evidence shows that endothelial cell metabolism instead governs angiogenesis. More specifically, 6-phosphofructo-2-kinase/fructose-2,6- bisphosphatase 3 (PFKFB3) determines blood vessel development. Therefore, we aim to improve pulp regeneration and neovascularization by overexpressing PFKFB3 in DPSCs. In a first part of the project, we characterize the angiogenic properties of PFKFB3-overexpressing DPSCs (PDPSCs) in vitro. Secondly, we investigate whether these P-DPSCs are able to induce blood vessel development in vivo, in a mouse hindlimb ischemia model. The final and ultimate objective is the application of P-DPSCs in a mouse model of dental pulp regeneration. We hope that this project and the obtained insights might ultimately lead to the development of better pulp replacement strategies.

01 October 2016 - 30 September 2020