Therapeutic Potential of Induced Neural Stem Cells for Spinal Cord Injury

Transplantation of neural stem cells (NSCs) holds great potential for the treatment of spinal cord injury (SCI). However, transplanted NSCs poorly survive in the SCI environment. We injected NSCs into tibial nerve and transplanted tibial nerve into a hemisected spinal cord and investigated the effects of lithium chloride (LiCl) on the survival of spinal neurons, axonal regeneration, and functional recovery. Our results show that most of the transplanted NSCs expressed glial fibrillary acidic protein, while there was no obvious expression of nestin, neuronal nuclei, or acetyltransferase found in NSCs. LiCl treatment produced less macrosialin (ED1) expression and axonal degeneration in tibial nerve after NSC injection. Our results also show that a regimen of LiCl treatment promoted NSC differentiation into NF200-positive neurons with neurite extension into the host spinal cord. The combination of tibial nerve transplantation with NSCs and LiCl injection resulted in more host motoneurons surviving in the spinal cord, more regenerated axons in tibial nerve, less glial scar area, and decreased ED1 expression. We conclude that lithium may have therapeutic potential in cell replacement strategies for central nervous system injury due to its ability to promote survival and neuronal generation of grafted NSCs and reduced host immune reaction.

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Effects of estrogen on Survival and Neuronal Differentiation of adult human olfactory bulb neural stem Cells Transplanted into Spinal Cord Injured Rats

10.1101/571950 ◽

2019 ◽

Author(s):

S Rezk ◽

A Althani ◽

A Abd-Elmaksoud ◽

M Kassab ◽

A Farag ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Olfactory Bulb ◽

Neural Stem Cells ◽

Motor Neurons ◽

Therapeutic Potential ◽

Motor Functions ◽

Cord Injury ◽

Neuroprotective Therapy

AbstractIn the present study we developed an excitotoxic spinal cord injury (SCI) model using kainic acid (KA) to evaluate of the therapeutic potential of human olfactory bulb neural stem cells (h-OBNSCs) for spinal cord injury (SCI). In a previous study, we assessed the therapeutic potential of these cells for SCI; all transplanted animals showed successful engraftment. These cells differentiated predominantly as astrocytes, not motor neurons, so no improvement in motor functions was detected. In the current study we used estrogen as neuroprotective therapy before transplantation of OBNSCs to preserve some of endogenous neurons and enhance the differentiation of these cells towards neurons. The present work demonstrated that the h-GFP-OBNSCs were able to survive for more than eight weeks after sub-acute transplantation into injured spinal cord. Stereological quantification of OBNSCs showed approximately a 2.38-fold increase in the initial cell population transplanted. 40.91% of OBNSCs showed differentiation along the neuronal lineages, which was the predominant fate of these cells. 36.36% of the cells differentiated into mature astrocytes; meanwhile 22.73% of the cells differentiated into oligodendrocytes. Improvement in motor functions was also detected after cell transplantation.

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Transplantation of Induced Neural Stem Cells Derived from Human Fibroblasts Promotes Functional Recovery of Spinal Cord Injury in Rats

Neurology and Neurobiology ◽

10.31487/j.nnb.2020.03.12 ◽

2020 ◽

pp. 1-8

Author(s):

Sahar Kiani ◽

Atiyeh Mohammadshirazi ◽

Maedeh Kashkouli ◽

Ebrahim Shahbazi ◽

Hassan Asghari ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Neural Stem Cells ◽

Human Fibroblasts ◽

Sensory Loss ◽

Cell Based Therapy ◽

Cord Injury ◽

And Migration ◽

Induced Neural Stem Cells

Background: Traumatic injury to the spinal cord causes cell death, demyelination, axonal degeneration, and cavitation, resulting in functional motor and sensory loss. Stem cell therapy as a promising approach for spinal cord injury (SCI) has some challenges, such as immunological responses to grafted cells. Transplantation of autologous trans-differentiated cells can be a useful strategy to overcome this problem. Materials and Methods: In this research, we transplanted human-induced neural stem cells (hiNSCs), which were trans-differentiated from adult human fibroblasts into the injured spinal cord of adult rats on day seven post-injury. Before transplantation, hiNSCs were explored for expressing NSCs general protein and genes and also, their normal karyotype was examined. After hiNSCs transplantation, behavioural tests (BBB score and grid walk tests) were performed weekly and finally histological assessment was done for exploring the cell fates and migration. Results: Our results showed the cell viability, differentiation, and migration of transplanted hiNSCs was significantly improved in the injured site of the spinal cord up to seven weeks after the SCI. Also, the behavioural analysis revealed the enhanced locomotor functions of the animals that underwent transplantation after seven weeks. Our data provide strong evidence in support of the feasibility of hiNSCs for cell-based therapy in SCI rats.

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Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injury

Neural Regeneration Research ◽

10.4103/1673-5374.147953 ◽

2014 ◽

Vol 9 (24) ◽

pp. 2197 ◽

Cited By ~ 16

Author(s):

Lifeng Yang ◽

Zhi Li ◽

Wei Zhao ◽

Wei Liu ◽

Ye Zhou ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Neural Stem Cells ◽

Cord Injury ◽

Induced Neural Stem Cells

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Stem Cell Transplantation: A Promising Therapy for Spinal Cord Injury

Current Stem Cell Research & Therapy ◽

10.2174/1574888x14666190823144424 ◽

2020 ◽

Vol 15 (4) ◽

pp. 321-331 ◽

Cited By ~ 2

Author(s):

Zhe Gong ◽

Kaishun Xia ◽

Ankai Xu ◽

Chao Yu ◽

Chenggui Wang ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Therapeutic Potential ◽

Embryonic Stem ◽

Current Status ◽

Cord Injury

Spinal Cord Injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESCs), Mesenchymal Stem Cells (MSCs) and Neural Progenitor Cells (NPCs) /Neural Stem Cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cellbased therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize the current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.

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