scholarly journals Amelioration of Penetrating Ballistic-Like Brain Injury Induced Cognitive Deficits after Neuronal Differentiation of Transplanted Human Neural Stem Cells

2017 ◽  
Vol 34 (11) ◽  
pp. 1981-1995 ◽  
Author(s):  
Markus S. Spurlock ◽  
Aminul I. Ahmed ◽  
Karla N. Rivera ◽  
Shoji Yokobori ◽  
Stephanie W. Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Injury ◽  
Neural Stem Cells ◽  
Neuronal Differentiation ◽  
Cognitive Deficits ◽  
Human Neural Stem Cells

scholarly journals Freshly Thawed Cryobanked Human Neural Stem Cells Engraft within Endogenous Neurogenic Niches and Restore Cognitive Function Following Chronic Traumatic Brain Injury

2020 ◽  
Author(s):  
Anna Badner ◽  
Emily K. Reinhardt ◽  
Theodore V. Nguyen ◽  
Nicole Midani ◽  
Andrew T. Marshall ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Brain Injury ◽  
Neural Stem Cells ◽  
Spatial Learning ◽  
Risk Taking ◽  
Mechanisms Of Action ◽  
Human Neural Stem Cells ◽  
Risk Taking Behavior

AbstractHuman neural stem cells (hNSCs) have potential as a cell therapy following traumatic brain injury (TBI). While various studies have demonstrated the efficacy of NSCs from on-going culture, there is a significant gap in our understanding of freshly thawed cells from cryobanked stocks – a more clinically-relevant source. To address these shortfalls, the therapeutic potential of our previously validated Shef-6.0 human embryonic stem cell (hESC)-derived hNSC line was tested following long-term cryostorage and thawing prior to transplant. Immunodeficient athymic nude rats received a moderate unilateral controlled cortical impact (CCI) injury. At 4-weeks post-injury, 6×105 freshly thawed hNSCs were transplanted into six injection sites (2 ipsi- and 4 contra-lateral) with 53.4% of cells surviving three months post-transplant. Interestingly, most hNSCs were engrafted in the meninges and the lining of lateral ventricles, associated with high CXCR4 expression and a chemotactic response to SDF1alpha (CXCL12). While some expressed markers of neuron, astrocyte, and oligodendrocyte lineages, the majority remained progenitors, identified through doublecortin expression (78.1%). Importantly, transplantation resulted in improved spatial learning and memory in Morris water maze navigation and reduced risk-taking behavior in an elevated plus maze. Investigating potential mechanisms of action, we identified an increase in ipsilateral host hippocampus cornu ammonis (CA) neuron survival, contralateral dentate gyrus (DG) volume and DG neural progenitor morphology as well as a reduction in neuroinflammation. Together, these findings validate the potential of hNSCs to restore function after TBI and demonstrate that long-term bio-banking of cells and thawing aliquots prior to use may be suitable for clinical deployment.Significance StatementThere is no cure for chronic traumatic brain injury (TBI). While human neural stem cells (hNSCs) offer a potential treatment, no one has demonstrated efficacy of thawed hNSCs from long-term cryobanked stocks. Frozen aliquots are critical for multisite clinical trials, as this omission impacted the use of MSCs for graft versus host disease. This is the first study to demonstrate the efficacy of thawed hNSCs, while also providing support for novel mechanisms of action – linking meningeal and ventricular engraftment to reduced neuroinflammation and improved hippocampal neurogenesis. Importantly, these changes also led to clinically relevant effects on spatial learning/memory and risk-taking behavior. Together, this new understanding of hNSCs lays a foundation for future work and improved opportunities for patient care.

S6K Promotes Dopaminergic Neuronal Differentiation Through PI3K/Akt/mTOR-Dependent Signaling Pathways in Human Neural Stem Cells

2015 ◽  
Vol 53 (6) ◽  
pp. 3771-3782 ◽  
Author(s):  
Jeong Eun Lee ◽  
Mi Sun Lim ◽  
Jae Hyun Park ◽  
Chang Hwan Park ◽  
Hyun Chul Koh
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Signaling Pathways ◽  
Neuronal Differentiation ◽  
Human Neural Stem Cells

scholarly journals Efficient and Fast Differentiation of Human Neural Stem Cells from Human Embryonic Stem Cells for Cell Therapy

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Xinxin Han ◽  
Liming Yu ◽  
Jie Ren ◽  
Min Wang ◽  
Zhongliang Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Injury ◽  
Cell Therapy ◽  
Neural Stem Cells ◽  
Embryonic Stem ◽  
Great Promise ◽  
Marker Genes ◽  
Differentiation Potential ◽  
Human Neural Stem Cells ◽  
Hes Cells

Stem cell-based therapies have been used for repairing damaged brain tissue and helping functional recovery after brain injury. Aberrance neurogenesis is related with brain injury, and multipotential neural stem cells from human embryonic stem (hES) cells provide a great promise for cell replacement therapies. Optimized protocols for neural differentiation are necessary to produce functional human neural stem cells (hNSCs) for cell therapy. However, the qualified procedure is scarce and detailed features of hNSCs originated from hES cells are still unclear. In this study, we developed a method to obtain hNSCs from hES cells, by which we could harvest abundant hNSCs in a relatively short time. Then, we examined the expression of pluripotent and multipotent marker genes through immunostaining and confirmed differentiation potential of the differentiated hNSCs. Furthermore, we analyzed the mitotic activity of these hNSCs. In this report, we provided comprehensive features of hNSCs and delivered the knowledge about how to obtain more high-quality hNSCs from hES cells which may help to accelerate the NSC-based therapies in brain injury treatment.

Electroconductive nanoscale topography for enhanced neuronal differentiation and electrophysiological maturation of human neural stem cells

Nanoscale ◽  
2017 ◽  
Vol 9 (47) ◽  
pp. 18737-18752 ◽  
Author(s):  
Kisuk Yang ◽  
Seung Jung Yu ◽  
Jong Seung Lee ◽  
Hak-Rae Lee ◽  
Gyeong-Eon Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neuronal Differentiation ◽  
Neural Stem Cell ◽  
Human Neural Stem Cells ◽  
Nanoscale Topography

Electroconductive nanotopography for enhanced neurogenesis of neural stem cell.

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