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ABSTRACT: Although human amnion derived mesenchymal stem cells (AMSC) are a promising source of stem cells, their therapeutic potential for traumatic brain injury (TBI) has not been widely investigated. In this study, we evaluated the therapeutic potential of AMSC using a rat TBI model. AMSC were isolated from human amniotic membrane and characterized by flow cytometry. After induction, AMSC differentiated in vitro into neural stem-like cells (AM-NSC) that expressed higher levels of the neural stem cell markers, nestin, sox2 and musashi, in comparison to undifferentiated AMSC. Interestingly, the neurotrophic factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), glial cell derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) were markedly upregulated after neural stem cell induction. Following transplantation in a rat TBI model, significant improvements in neurological function, brain tissue morphology, and higher levels of BDNF, NGF, NT-3, GDNF and CNTF, were observed in the AM-NSC group compared with the AMSC and Matrigel groups. However, few grafted cells survived with minimal differentiation into neural-like cells. Together, our results suggest that transplantation of AM-NSC promotes functional rehabilitation of rats with TBI, with enhanced expression of neurotrophic factors a likely mechanistic pathway.
Neurochemical Research 03/2013; · 2.24 Impact Factor
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Jian You, Sun-Quan Hong,
Mao-Ying Zhang,
Hai-Lin Zhao,
Tian-Zhu Liu,
Hong-Long Zhou,
Ying-Qian Cai,
Zhi-Min Xu,
Yang Guo,
Xiao-Dan Jiang,
Ru-Xiang Xu
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ABSTRACT: Tenascin-R (TN-R) is a neural specific protein and an important molecule involved in inhibition of axonal regeneration after spinal cord injury (SCI). Here we report on rabbit-derived TN-R polyclonal antibody, which acts as a TN-R antagonist with high titer and high specificity, promoted neurite outgrowth and sprouting of rat cortical neurons cultured on the inhibitory TN-R substrate in vitro. When locally administered into the lesion sites of rats received spinal cord dorsal hemisection, these TN-R antibodies could significantly decrease RhoA activation and improve functional recovery from corticospinal tract (CST) transection. Thus, passive immunotherapy with specific TN-R antagonist may represent a promising repair strategy following acute SCI.
Neuroscience Letters 08/2012; 525(2):129-34. · 2.11 Impact Factor
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ABSTRACT: Transdifferentiated and untransdifferentiated mesenchymal stem cells (MSCs) have shown therapeutic benefits in central nervous system (CNS) injury. However, it is unclear which would be more appropriate for transplantation. To address this question, we transplanted untransdifferentiated human umbilical mesenchymal stem cells (HUMSCs) and transdifferentiated HUMSCs (HUMSC-derived neurospheres, HUMSC-NSs) into a rat model of traumatic brain injury. Cognitive function, cell survival and differentiation, brain tissue morphology and neurotrophin expression were compared between groups. Significant improvements in cognitive function and brain tissue morphology were seen in the HUMSCs group compared with HUMSC-NSs group, which was accompanied by increased neurotrophin expression. Moreover, only few grafted cells survived in both the HUMSCs and HUMSC-NSs groups, with very few of the cells differentiating into neural-like cells. These findings indicate that HUMSCs are more appropriate for transplantation and their therapeutic benefits may be associated with neuroprotection rather than cell replacement.
Neurochemical Research 08/2011; 36(12):2391-400. · 2.24 Impact Factor
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ABSTRACT: An animal model for clip spinal cord injury (SCI) was used to determine whether Neurotrophin-3 (NT-3) genetically modified human umbilical mesenchymal stem cells (NT-3-HUMSCs) could promote the morphologic and functional recovery of injured spinal cords. Using the Basso, Beattie, and Bresnahan scores and a grid test, the rats in the HUMSC-treated and NT-3-HUMSCs groups had significantly improved locomotor functional recovery more than the control group. In comparison, the NT-3-HUMSCs group achieved better functional recovery than the HUMSCs group at the end of 12 weeks after SCI. The functional recovery was accompanied by increased intensity of 5-HT fibers, increased volume of spared myelination, and decreased area of the cystic cavity in the NT-3-HUMSCs group compared with the HUMSCs group. Moreover, transplanted NT-3-HUMSCs survived and produced larger amounts of NT-3 than the HUMSCs in the host spinal cord. These results show that NT-3 enhanced the therapeutic effects of HUMSCs after clip injury of the spinal cord.
Brain research 03/2011; 1391:102-13. · 2.46 Impact Factor
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ABSTRACT: An animal model of transected spinal cord injury (SCI) was used to test the hypothesis that cografted human umbilical mesenchymal stem cells-derived neurospheres (HUMSC-NSs) and BDNF can promote morphologic and functional recoveries of injured spinal cord. In vitro, HUMSC-NSs terminally differentiated into higher percentages of cells expressing neuronal markers: beta-tubulin III and MAP2ab by the supplement with BDNF. Following grafted into injured spinal cord, very few grafted cells survived in the HUMSC-NSs + BDNF-treated (<3%) and HUMSC-NSs-treated (<1%) groups. The survived cells were differentiated into various cells, which were confirmed by double staining of BrdU and neural or glia markers. In comparison, more grafted cells in the HUMSC-NSs + BDNF group transformed into mature neural-like cells, while more grafted cells in the HUMSC-NSs group transformed into oligodendrocyte-like cells. HUMSC-NSs + BDNF-treated group had more greatly improved BBB scores, compared with HUMSC-NSs-treated and medium-treated groups. Additionally, axonal regeneration showed significant improvement in rats receiving HUMSC-NSs + BDNF, compared with HUMSC-NSs-treated and medium-treated groups, as demonstrated by the NF-200-positive staining and Fluorogold (FG) retrograde tracing study. Lastly, a significant reduction in the percentage cavitation was seen in the two cell-treated groups compared with medium control group. These results means BDNF could promote the neural differentiation of HUMSC-NSs in vitro and in vivo. However, cellular replacement is unlikely to explain the improvement in functional outcome. The functional recovery might more rely on the axonal regeneration and neuroprotective action that active by the grafted cells. Cografted HUMSCs and BDNF is a potential therapy for SCI.
Neurochemical Research 05/2009; 34(11):2030-9. · 2.24 Impact Factor
