Abstract
Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population with high self-renewal ability that originates from the cranial neural crest. Since SHED are homologous to the central nervous system, they possess superior capacity to differentiate into neural cells. However, whether and how SHED ameliorate degenerative central nervous disease are unclear. Chronic cerebral ischemia (CCI) is a kind of neurological disease caused by long-term cerebral circulation insufficiency and is characterized by progressive cognitive and behavioral deterioration. In this study, we showed that either systemic transplantation of SHED or SHED infusion into the hippocampus ameliorated cognitive impairment of CCI rats in four weeks after SHED treatment by rescuing the number of neurons in the hippocampus area. Mechanistically, SHED transplantation decreased the apoptosis of neuronal cells in the hippocampus area of CCI rats through downregulation of cleaved caspase-3. In summary, SHED transplantation protected the neuronal function and reduced neuronal apoptosis, resulting in amelioration of cognitive impairment from CCI. Our findings suggest that SHED are a promising stem cell source for cell therapy of neurological diseases in the clinic.
Highlights
Chronic cerebral ischemia (CCI) is considered both a neurological and cerebrovascular disease and is characterized by progressive cognitive and behavioral deterioration caused by long-term cerebral blood perfusion insufficiency
Flow cytometric analysis showed that Stem cells from human exfoliated deciduous teeth (SHED) expressed Mesenchymal stem cells (MSCs) surface markers, such as CD73 (98.89%), CD90 (98.52%), and CD105 (97.62%) but did not express hematopoietic markers, such as CD34 (0.5%) and CD45 (0.2%) (Figures 2(a) and 2(b))
We demonstrated that SHED transplantation protected neuronal cells and ameliorated cognitive functions in CCI rats when injected into the hippocampus or through the tail vein
Summary
Chronic cerebral ischemia (CCI) is considered both a neurological and cerebrovascular disease and is characterized by progressive cognitive and behavioral deterioration caused by long-term cerebral blood perfusion insufficiency. Multiple therapeutic mechanisms may underlie the effects of MSCT-based therapies, including direct differentiating into functional neurons, paracrine effects, and interplay between MSCs and immune cells. Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population with high self-renewal ability that originates from the cranial neural crest. We used a rat model with two-vessel occlusion, a classical CCI model, to investigate the treatment effects of SHED transplantation, in which memory and neuronal functions of a CCI model were evaluated, and we further explored the underlying mechanisms. Our data showed that SHED transplantation decreased cognitive impairment of CCI rats and protected the cell functions of neurons by reducing cell apoptosis
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