Abstract
Angiogenesis/vasculogenesis and neurogenesis are critical for dentin and pulp regeneration. We have isolated pulp CD 31− SP cells and CD 105＋cells with multi-lineage differentiation potential and high migratory and proliferation potential. In models of mouse hindlimb ischemia, local transplantation of these pulp stem cells resulted in an increase in the blood flow including high density of capillary formation. The transplanted cells were in proximity of the newly formed vasculature without incorporating into vessels, and expressed several proangiogenic factors.These results suggested a potential utility of these subfractions of human dental pulp stem/progenitor cells to stimulate angiogenesis/vasculogenesis during tissue regeneration. The conditioned medium from these pulp stem cells demonstrated mitogenic and anti-apoptotic activities on endothelial cells,suggesting trophic actions on angiogenesis/vasculogenesis in the hindlimb ischemia. In the transplantation of these cells into the cerebral ischemic model neuronal progenitor cells migrated to the penumbra, followed by enhanced differentiation into neuron with high expression of neurotrophic factors.The functional outcome was improved.Autologous transplantation of the CD 31− SP cells into an in vivo model of amputated pulp resulted in complete regeneration of pulp tissue with capillaries and neuronal processes. Furthermore,the transplantation of CD 31− SP cells or CD 105＋cells with SDF-1 into root canals after whole pulp removal of mature apicoectomized teeth resulted in complete regeneration of pulp replete with nerves and vasculature by day 14. The qualitative and quantitative protein and mRNA expression patterns of the regenerated pulp were similar to those of normal pulp.These results suggested a potential utility of these dental pulp stem/progenitor cells to stimulate pulp regeneration.
