Operators were also not blinded to the conditions of the experiments. growth factor-a. The effect could be amplified by exposing dental pulp stem cell to stromal-derived factor 1, which stimulates vascular endothelial growth factor-a expression. These findings support the use of dental pulp stem cell in therapy for stroke. strong class=”kwd-title” Keywords: Dental pulp stem cells, bloodCbrain barrier, vascular endothelial growth factor, stromal-derived factor 1, in?vitro Introduction The chronic cognitive and motorCsensory dysfunction resulting from stroke presents a major challenge to healthcare in much of the developed world. As of 2010, there were approximately 33 million people living with the effects of stroke, making stroke responsible for 4% of the total disability-adjusted life years of disease burden.1 Given the scope of this issue, it is clear that much importance must be placed on developing efficacious treatments to return patients to a healthy and functional state. Cell-based therapy is usually emerging as a possible treatment option for stroke.2 This field of study was sparked by the ability of stem cells to populate areas and SX-3228 replace the function of many divergent tissue types. Transplantation of stem cells provides the potential to extend the post-stroke recovery of function beyond what is possible by endogenous recovery alone. This has been exhibited over the last decade in animal models.2C6 However, this effect is not well explained by the tissue replacement model alone. The paracrine secretion of various factors may underlie the functional improvement seen in animal stroke models of cell-based therapy whereby immunomodulation, neuroprotection, neurogenesis, neuroplasticity and angiogenesis are supported and enhanced.7 Research into cell-based therapy for stroke has advanced to a point where a number of early phase clinical trials have been undertaken.8C11 However, several basic questions remain unanswered, with the focus from this study being on how stem cells SX-3228 may transmigrate the bloodCbrain barrier (BBB) if administered via the vasculature. One potential source of stem cells for therapy is usually dental pulp stem cell (DPSC), which was first described by Gronthos et?al.12 These are a population of highly Rabbit Polyclonal to GPRC6A proliferative, undifferentiated cells residing in perivascular niches within the dental pulp of adult teeth. DPSCs have been demonstrated to have the capacity to differentiate into neurons, adipocytes, myocytes and chondrocytes in?vitro.13C15 Intracerebral (IC) transplantation following stroke in a rat model showed an improvement in functional outcomes.2 There are two paradigms for the administration of therapeutic stem cells in stroke research: intravascular (IV) and IC. IC transplantation delivers stem cells directly to the site of damage, which may result in a greater surviving population of viable cells. However, this is a highly invasive procedure and is associated with an increased mortality rate of approximately 10% when administered acutely in rodent stroke models.2 As such, acute IC transplantation may SX-3228 not be a clinically viable model. IV administration of stem cells in animal models of stroke has been validated as efficacious. It has even been exhibited in some studies that small populations of transplanted stem cells can be detected within the brain parenchyma.5 A likely mechanism for this is usually that stem cells migrate along a stromal-derived factor-1 (SDF-1) gradient towards the ischaemic SX-3228 border zone via the receptor CXCR4. SDF-1 is usually upregulated for at least a month following stroke, so the effective window for treatment could hypothetically be extended significantly.16,17 However, this depends on how stem cells interact with the SX-3228 BBB. The BBB refers to the specialized structure of the neurovascular unit. The BBB is composed of a continuous layer of endothelial cells, which are surrounded by a basement membrane, pericytes and astrocyte processes. The main function of the BBB is usually to segregate the environment of the brain parenchyma from peripheral circulation. In general, the BBB is usually selectively impermeable to large polar molecules and cells.18 The mechanisms by which stem cells transmigrate the BBB have not yet been fully characterized. It.