Angiogenic properties of human dental pulp stem cells (hDPSC)

Objectives: Since the currently used prostheses are prone to biological and mechanical failure and inorganic pulp replacement materials often lead to pulp necrosis, there is an urgent need for new pulp regeneration strategies. Recently, adult mesenchymal stem cells have been isolated from tooth dental pulp tissue. These human dental pulp stem cells (hDPSC) have the capacity for multilineage differentiation into cell types such as chondrocytes, osteoblasts and neural-like cells and are currently evaluated in clinical trials for bone tissue engineering. Moreover, this stem cell population has been suggested to provide an effective strategy for pulp regeneration. As neovascularisation is a crucial event for the success of pulp tissue regeneration, we investigated into detail the angiogenic activities of hDPSC.

Methods: We evaluated the angiogenic proteins produced by the hDPSC by means of an antibody array. The results of this array were validated by ELISA and RT-PCR. Furthermore the biological effects of the hDSPC on mouse brain endothelial cells (MBEC) were investigated with an in vitro proliferation and migration assay.

Results: Numerous angiogenic factors such as vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), fibroblast growth factor-2 (FGF-2) are highly expressed by these stem cells. Also anti-angiogenic factors such as endostatin and TIMP-1 were found in the conditioned medium of the hDPSC. Moreover, hDPSC significantly induced MBEC migration in vitro, while no effect on MBEC proliferation could be found.

Conclusions: Our data clearly show that hDPSC are able to induce angiogenesis in vitro, particularly endothelial cell migration. In the future, the potential effect of hDPSC on the endothelial survival and tube forming capacity will be investigated. If hDPSC are able to contribute to vascular networks, this will have great therapeutic potential, not only in terms of pulp regeneration, but also as a cell-based therapy for stroke and myocardial infarctions.