Angiogenic Properties of Human Dental Pulp Stem Cells

Abstract

Angiogenesis, the formation of capillaries from pre-existing blood vessels, is a key process in tissue engineering. If blood supply cannot be established rapidly, there is insufficient oxygen and nutrient transport and necrosis of the implanted tissue will occur. Recent studies indicate that the human dental pulp contains precursor cells, named dental pulp stem cells (hDPSC) that show self-renewal and multilineage differentiation capacity. Since these cells can be easily isolated, cultured and cryopreserved, they represent an attractive stem cell source for tissue engineering. Until now, only little is known about the angiogenic abilities and mechanisms of the hDPSC. In this study, the angiogenic profile of both cell lysates and conditioned medium of hDPSC was determined by means of an antibody array. Numerous pro-and anti-angiogenic factors such as vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1) and endostatin were found both at the mRNA and protein level. hDPSC had no influence on the proliferation of the human microvascular endothelial cells (HMEC-1), but were able to significantly induce HMEC-1 migration in vitro. Addition of the PI3K-inhibitor LY294002 and the MEK-inhibitor U0126 to the HMEC-1 inhibited this effect, suggesting that both Akt and ERK pathways are involved in hDPSC-mediated HMEC-1 migration. Antibodies against VEGF also abolished the chemotactic actions of hDPSC. Furthermore, in the chicken chorioallantoic membrane (CAM) assay, hDPSC were able to significantly induce blood vessel formation. In conclusion, hDPSC have the ability to induce angiogenesis, meaning that this stem cell population has a great clinical potential, not only for tissue engineering but also for the treatment of chronic wounds, stroke and myocardial infarctions.

Osteoinductive Activity of Bone Scaffold Bioceramic Companied with Control Release of VEGF Protein Treated Dental stem cells as A New Concept for Bone Regeneration: Part II

“…Dental stem cells (DSCs) have great potential in bone tissue strategies because of their high proliferative ability 4) . Another advantage of DSCs is the decreased morbidity during their harvesting since they are derived from extracted teeth 5) . These cells also have the capability of self-renewal and pluripotential differentiation capacity 6) .…”

“…DSCs are considered excellent candidate stem cells for hard and soft tissue regeneration and organ transplantation in BTE 4) . Easy isolation, culturing and cryopreservation with retained multipotential differentiation make them an attractive source of stem cell for tissue engineering capability to generating bone beside dental tissue 5,7) . Diseases that cause loss of substances or volume and tissue damage is now treated effectively with the combination of cell-based therapy and regenerative medicine 8) .…”

“…In BTE studies, the most widely studied MSC types are bone marrow-MSCs and adipose-derived MSCs, which display similar results 8) . However, pain, morbidity and decreased cell count after harvest are the major problems associated with bone marrow -MSCs, alternative sources such as adipose tissue-derived for MSCs have been explored 5,6) . Gronthos et al 11) for the first time isolated DSCs in 2000.…”

“…The biological relationship of DSCs with diff erent types of scaff olds needs to be analyzed 17) . Oxygen and nutrient supply to the implanted cells is a key for successful tissue engineering 5) . Failure in the rapid formation of blood vessels of the transplanted tissue leads to necrosis 18) .…”

“…Failure in the rapid formation of blood vessels of the transplanted tissue leads to necrosis 18) . The ability of DSCs to induce angiogenesis and osteogenesis should be investigated to make these cells beneficial for tissue engineering 5) . The use of DSCs is not only limited to the dental fi eld as these cells can also be used as a source of stem cell for general bone regeneration 19) .…”