Neurotrophin Expressions in Neural Stem Cells Grafted Acutely to Transected Spinal Cord of Adult Rats Linked to Functional Improvement

Gu, Yingli; Yin, Luwei; Zhang, Zhuo; Liu, Jia; Liu, Sujuan; Zhang, Lianfeng; Wang, Ting‐Hua

doi:10.1007/s10571-012-9832-4

Cited by 40 publications

(26 citation statements)

References 32 publications

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“…Despite these parameters are not absolute (due to culture variability), they generally refl ect characteristics of culture growth and state of stem cells in the fetuses of different gestation ages. These results are consistent with the known data and supplement the previously reported observation that the number and rate of neurosphere formation depend on gestational age of the fetus [12,15].…”

Section: Resultssupporting

confidence: 93%

“…Complex therapeutic effect of neural stem and progenitor cells (NSPC) is determined by migration capacity of these cells, their trophic activity [15,19], immunomodulating properties [9]. These properties of stem and progenitor cells are formed during in vivo development and differentiation of the neural tissue and are maintained during NSPC culturing and expansion in vitro.…”

mentioning

confidence: 99%

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Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro

et al. 2016

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Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity. Detailed analysis of neural stem cell populations derived from fetuses on gestation weeks 8-9, 18-20, and 26 expressing Lex/SSEA1 was performed.

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Section: Resultssupporting

confidence: 93%

mentioning

confidence: 99%

Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro

et al. 2016

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“…Neurotrophins have been shown to convey benefit following neurotrauma; cell therapies that focus on delivery of these factors can improve functional outcome [35]. We examined a series of neurotrophic gene markers in mRNA isolated from dNSCs and following in vitro differentiation conditions.…”

Section: Neurotrophic Factor Expression Capacity Of Ips-dnscmentioning

confidence: 99%

Transplantation of Induced Pluripotent Stem Cell-Derived Neural Stem Cells Mediate Functional Recovery Following Thoracic Spinal Cord Injury Through Remyelination of Axons

Salewski

Mitchell

et al. 2015

Stem Cells Translational Medicine

149

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Neural stem cells (NSCs) from embryonic or fetal/adult tissue sources have shown considerable promise in regenerative strategies for traumatic spinal cord injury (SCI). However, there are limitations with their use related to the availability, immunogenicity, and uncertainty of the mechanisms involved. To address these issues, definitive NSCs derived from induced pluripotent stem (iPS) cells generated using a nonviral, piggyBac transposon approach, were investigated. Committed NSCs were generated from iPS cells using a free-floating neurosphere methodology previously described by our laboratory. To delineate the mechanism of action, specifically the role of exogenous myelination, NSCs derived from wildtype (wt) and nonmyelinating Shiverer (shi) iPS cell lines were used following thoracic SCI with subacute intraspinal transplantation. Behavioral, histological, and electrophysiological outcomes were analyzed to assess the effectiveness of this treatment. The wt-and shi-iPS-NSCs were validated and shown to be equivalent except in myelination capacity. Both iPS-NSC lines successfully integrated into the injured spinal cord and predominantly differentiated to oligodendrocytes, but only the wt-iPS-NSC treatment resulted in a functional benefit. The wt-iPS-dNSCs, which exhibited the capacity for remyelination, significantly improved neurobehavioral function (Basso Mouse Scale and CatWalk), histological outcomes, and electrophysiological measures of axonal function (sucrose gap analysis) compared with the nonmyelinating iPS-dNSCs and cell-free controls. In summary, we demonstrated that iPS cells can generate translationally relevant NSCs for applications in SCI. Although NSCs have a diverse range of functions in the injured spinal cord, remyelination is the predominant mechanism of recovery following thoracic SCI. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:743-754 SIGNIFICANCEGain-of-function/loss-of-function techniques were used to examine the mechanistic importance of graft-derived remyelination following thoracic spinal cord injury (SCI). The novel findings of this study include the first use of neural stem cells (NSCs) from induced pluripotent stem cells (iPSCs) derived using the clonal neurosphere expansion conditions, for the treatment of SCI, the first characterization and in vivo application of iPSCs from Shiverer mouse fibroblasts, and the first evidence of the importance of remyelination by pluripotent-sourced NSCs for SCI repair and regeneration.

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“…The ordinarily used cell categories contain embryonic stem cells (ESCs), neural stem cells (NSCs), olfactory ensheathing cells (OECs), and bone marrow stromal cells (BMSCs) (Nori et al 2011;Gorrie et al 2010;Karamouzian et al 2012;Gu et al 2012). However, some issues limited the clinical application of these cells.…”

Section: Introductionmentioning

confidence: 99%

Adipose-Derived Stem Cells Expressing the Neurogenin-2 Promote Functional Recovery After Spinal Cord Injury in Rat

Tang

Zhu

et al. 2015

Cell Mol Neurobiol

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Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. This study aimed to investigate whether the use of adipose-derived stem cells (ADSCs) over-expressing the Ngn2 transgene (Ngn2-ADSCs) could display the characteristics of neurogenic cells and improve functional recovery in an experimental rat model of SCI. ADSCs from rats were cultured and purified in vitro, followed by genetically modified with the Ngn2 gene. Forty-eight adult female Sprague-Dawley rats were randomly assigned to three groups: the control, ADSCs, and Ngn2-ADSCs groups. The hind-limb motor function of all rats was recorded using the Basso, Beattie, and Bresnahan locomotor rating scale for 8 weeks. Moreover, hematoxylineosin staining and immunohistochemistry were also performed. After neural induction, positive expression rate of NeuN in Ngn2-ADSCs group was upon 90 %. Following transplantation, a great number of ADSCs was found around the center of the injury spinal cord at 1 and 4 weeks, which improved retention of tissue at the lesion site. Ngn2-ADSCs differentiated into neurons, indicated by the expression of neuronal markers, NeuN and Tuj1. Additionally, transplantation of Ngn2-ADSCs upregulated the trophic factors (brain-derived neurotrophic factor and vascular endothelial growth factor), and inhibited the glial scar formation, which was indicated by immunohistochemistry with glial fibrillary acidic protein. Finally, Ngn2-ADSCs-treated animals showed the highest functional recovery among the three groups. These findings suggest that transplantation of Ngn2-overexpressed ADSCs promote the functional recovery from SCI, and improve the local microenvironment of injured cord in a more efficient way than that with ADSCs alone.

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Neurotrophin Expressions in Neural Stem Cells Grafted Acutely to Transected Spinal Cord of Adult Rats Linked to Functional Improvement

Cited by 40 publications

References 32 publications

Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro

Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro

Transplantation of Induced Pluripotent Stem Cell-Derived Neural Stem Cells Mediate Functional Recovery Following Thoracic Spinal Cord Injury Through Remyelination of Axons

Adipose-Derived Stem Cells Expressing the Neurogenin-2 Promote Functional Recovery After Spinal Cord Injury in Rat

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