Isolation and Characterization of Two Kinds of Stem Cells from the Same Human Skin Back Sample with Therapeutic Potential in Spinal 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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Therapeutic potential of human olfactory bulb neural stem cells for spinal cord injury in rats

Spinal Cord ◽

10.1038/sc.2016.14 ◽

2016 ◽

Vol 54 (10) ◽

pp. 785-797 ◽

Cited By ~ 6

Author(s):

H E Marei ◽

A Althani ◽

S Rezk ◽

A Farag ◽

S Lashen ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Olfactory Bulb ◽

Neural Stem Cells ◽

Therapeutic Potential ◽

Cord Injury

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PEP-1-SOD1 Improves the Therapeutic Potential of Transplanted Adipose-Derived Mesenchymal Stem Cells in Spinal Cord Injury

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2017.1686 ◽

2017 ◽

Vol 7 (12) ◽

pp. 1313-1318

Author(s):

Wei Wang ◽

Hao Peng

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Mesenchymal Stem Cells ◽

Therapeutic Potential ◽

Cord Injury

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Syngeneic, in contrast to allogeneic, mesenchymal stem cells have superior therapeutic potential following spinal cord injury

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2018.11.005 ◽

2019 ◽

Vol 328 ◽

pp. 5-19

Author(s):

Ramil Hakim ◽

Ruxandra Covacu ◽

Vasilios Zachariadis ◽

Arvid Frostell ◽

Sreenivasa Sankavaram ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Mesenchymal Stem Cells ◽

Therapeutic Potential ◽

Cord Injury

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Preconditioning in lowered oxygen enhances the therapeutic potential of human umbilical mesenchymal stem cells in a rat model of spinal cord injury

Brain Research ◽

10.1016/j.brainres.2016.04.025 ◽

2016 ◽

Vol 1642 ◽

pp. 426-435 ◽

Cited By ~ 19

Author(s):

Zhou Zhilai ◽

Mo Biling ◽

Qiu Sujun ◽

Dong Chao ◽

Shi Benchao ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Mesenchymal Stem Cells ◽

Rat Model ◽

Therapeutic Potential ◽

Cord Injury ◽

Umbilical Mesenchymal Stem Cells

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Thermo-sensitive electroactive hydrogel combined with electrical stimulation for repair of spinal cord injury

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01031-y ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Wei Liu ◽

Yiqian Luo ◽

Cong Ning ◽

Wenjing Zhang ◽

Qingzheng Zhang ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Electrical Stimulation ◽

Tissue Repair ◽

Therapeutic Potential ◽

Electrical Conductance ◽

Continuous Release ◽

Cord Injury ◽

Cultured Nerve Cells

AbstractThe strategy of using a combination of scaffold-based physical and biochemical cues to repair spinal cord injury (SCI) has shown promising results. However, integrating conductivity and neurotrophins into a scaffold that recreates the electrophysiologic and nutritional microenvironment of the spinal cord (SC) remains challenging. In this study we investigated the therapeutic potential of a soft thermo-sensitive polymer electroactive hydrogel (TPEH) loaded with nerve growth factor (NGF) combined with functional electrical stimulation (ES) for the treatment of SCI. The developed hydrogel exhibits outstanding electrical conductance upon ES, with continuous release of NGF for at least 24 days. In cultured nerve cells, TPEH loaded with NGF promoted the neuronal differentiation of neural stem cells and axonal growth, an effect that was potentiated by ES. In a rat model of SCI, TPEH combined with NGF and ES stimulated endogenous neurogenesis and improved motor function. These results indicate that the TPEH scaffold that combines ES and biochemical cues can effectively promote SC tissue repair.

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Transplantation of a Peripheral Nerve with Neural Stem Cells Plus Lithium Chloride Injection Promote the Recovery of Rat Spinal Cord Injury

Cell Transplantation ◽

10.1177/0963689717752945 ◽

2018 ◽

Vol 27 (3) ◽

pp. 471-484 ◽

Cited By ~ 7

Author(s):

Li-Qun Zhang ◽

Wen-Ming Zhang ◽

Lingxiao Deng ◽

Zi-Xing Xu ◽

Wen-Bin Lan ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Neural Stem Cells ◽

Lithium Chloride ◽

Therapeutic Potential ◽

Tibial Nerve ◽

Neuronal Nuclei ◽

Cord Injury ◽

Licl Treatment

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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Comprehensive Effects of Suppression of MicroRNA-383 in Human Bone-Marrow-Derived Mesenchymal Stem Cells on Treating Spinal Cord Injury

Cellular Physiology and Biochemistry ◽

10.1159/000489756 ◽

2018 ◽

Vol 47 (1) ◽

pp. 129-139 ◽

Cited By ~ 1

Author(s):

Guo-Jun Wei ◽

Ke-wen Zheng ◽

Gang An ◽

Zuo-Wei Shi ◽

Kai-Fu Wang ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Bone Marrow ◽

Spinal Cord Injury ◽

Mesenchymal Stem Cells ◽

Therapeutic Potential ◽

Luciferase Reporter ◽

Therapeutic Effects ◽

Cord Injury

Background/Aims: Transplantation of bone-marrow-derived mesenchymal stem cells (MSCs) promotes neural cell regeneration after spinal cord injury (SCI). Recently, we showed that suppression of microRNA-383 (miR-383) in MSCs increased the protein levels of glial cell line derived neurotrophic factor (GDNF), resulting in improved therapeutic effects on SCI. However, the overall effects of miR-383 suppression in MSCs on SCI therapy were not determined yet. Here, we addressed this question. Methods: We used bioinformatics tools to predict all miR-383-targeting genes, confirmed the functional bindings in a dual luciferase reporter assay. The effects of alteration of candidate genes in MSCs on cell proliferation were analyzed by MTT assay and by Western blotting for PCNA. The effects on angiogenesis were assessed by HUVEC assay. The effects on SCI in vivo were analyzed by transplantation of the modified MSCs into nude rats that underwent SCI. Results: Suppression of miR-383 in MSCs not only upregulated GDNF protein, but also increased vascular endothelial growth factor A (VEGF-A) and cyclin-dependent kinase 19 (CDK19), two other miR-383 targets. MiR-383-suppression-induced increases in CDK19 resulted in a slight but significant increase in MSC proliferation, while miR-383-suppression-induced increases in VEGF-A resulted in a slight but significant increase in MSC-mediated angiogenesis. Conclusions: Upregulation of CDK19 and VEGF-A by miR-383 suppression in MSCs further improve the therapeutic potential of MSCs in treating SCI in rats.

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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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