Abstract
Stroke is a leading cause of permanent disability world-wide, but aside from rehabilitation, there is currently no clinically-proven pharmaceutical or biological agent to improve neurological disability. Cell-based therapies using stem cells, such as dental pulp stem cells, are a promising alternative for treatment of neurological diseases, including stroke. The ischaemic environment in stroke affects multiple cell populations, thus stem cells, which act through cellular and molecular mechanisms, are promising candidates. The most common stem cell population studied in the neurological setting has been mesenchymal stem cells due to their accessibility. However, it is believed that neural stem cells, the resident stem cell of the adult brain, would be most appropriate for brain repair. Using reprogramming strategies, alternative sources of neural stem and progenitor cells have been explored. We postulate that a cell of closer origin to the neural lineage would be a promising candidate for reprogramming and modification towards a neural stem or progenitor cell. One such candidate population is dental pulp stem cells, which reside in the root canal of teeth. This review will focus on the neural potential of dental pulp stem cells and their investigations in the stroke setting to date, and include an overview on the use of different sources of neural stem cells in preclinical studies and clinical trials of stroke.
Highlights
The central nervous system (CNS) functions through complex molecular and cellular interactions, and disruption by severe injury or disease leads to irreversible neuronal loss and associated functional deficits
At 4 weeks, significant neurobehavioural improvement was observed, only 2.3 percent of engrafted cells were detected. These results suggest that the improvement was not mediated by a cell replacement mechanism rather through a Dental pulp stem cells (DPSC)-dependent paracrine effect, involving the many growth factors secreted by DPSC, such as nerve growth factor, brain-derived neurotrophic
A reduction in post-stroke corpus callosum atrophy was observed, again indicating to the ability of DPSC to influence host axonal remodelling. These results demonstrate the role of SDF1 signalling in DPSC migration and neuroplasticity properties
Summary
The central nervous system (CNS) functions through complex molecular and cellular interactions, and disruption by severe injury or disease leads to irreversible neuronal loss and associated functional deficits. This review will focus on the potential use of human DPSC for stroke therapy and will include an overview of different types of NSC being studied. BDNF, brain-derived neurotrophic factor; bFGF, basic fibroblast growth factor; DMEM, Dulbecco’s Modified Eagle’s Medium; DPSC, dental pulp stem cell(s); EGF, epidermal growth factor; F12, Ham’s F12 nutrient mixture; FGF8, fibroblast growth factor 8; GDNF, glial cell-derived neurotrophic factor; IGF-I, insulin-like growth factor I; NGF, nerve growth factor; NT-3, neurotrophin-3.
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