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.
Highlights
Stem cell biology has become an important field for the understanding of tissue regeneration and provides a very powerful tool in the treatment of traumatic injuries and various lifethreatening pathological conditions, such as heart ischemia, spinal cord injury and Parkinson’s disease
These progenitor cells, designated human dental pulp stem cells, possess the capacity to differentiate into numerous cell types in vitro including odontoblasts [6], osteoblasts [5,7,8], chondroblasts [5,7,8], adipocytes [8], neuronal cells [9,10] and even hepatocyte-like cells [11]. hDPSC have several advantages for clinical applications compared to other adult mesenchymal stem cells as they can be isolated from extracted adult teeth
The objective of this study was to examine whether these stem cells, namely hDPSC, are able to induce angiogenesis and to elucidate the regulatory pathways involved in their potential proangiogenic actions
Summary
Stem cell biology has become an important field for the understanding of tissue regeneration and provides a very powerful tool in the treatment of traumatic injuries and various lifethreatening pathological conditions, such as heart ischemia, spinal cord injury and Parkinson’s disease. Mesenchymal stem cells isolated from the bone marrow (BM-MSC) are the most intensively studied adult stem cells They have been found to have clinical potential for gene therapy and for autologous repair of skeletal tissues, spinal cord injury and myocardial damages [1,2,3]. More than a decade ago, Gronthos et al demonstrated the existence of a MSC-like stem cell population within the dental pulp tissue [5] These progenitor cells, designated human dental pulp stem cells (hDPSC), possess the capacity to differentiate into numerous cell types in vitro including odontoblasts [6], osteoblasts [5,7,8], chondroblasts [5,7,8], adipocytes [8], neuronal cells [9,10] and even hepatocyte-like cells [11]. Recent studies indicate that hDPSC have a higher population doubling time, neural and epithelial stem cell properties than BM-MSC [13,14]
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