Polarized Macrophages Have Distinct Roles in the Differentiation and Migration of Embryonic Spinal-cord-derived Neural Stem Cells After Grafting to Injured Sites of Spinal Cord

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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BCOR Internal Tandem Duplication Expression in Neural Stem Cells Promotes Growth, Invasion, and Expression of PRC2 Targets

International Journal of Molecular Sciences ◽

10.3390/ijms22083913 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3913

Author(s):

Satoshi Nakata ◽

Ming Yuan ◽

Jeffrey A. Rubens ◽

Ulf D. Kahlert ◽

Jarek Maciaczyk ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Tandem Duplication ◽

Target Genes ◽

Cellular Growth ◽

Central Nervous System Tumor ◽

Internal Tandem Duplication ◽

Invasion And Migration ◽

Human Neural Stem Cells ◽

And Migration

Central nervous system tumor with BCL6-corepressor internal tandem duplication (CNS-BCOR ITD) is a malignant entity characterized by recurrent alterations in exon 15 encoding the essential binding domain for the polycomb repressive complex (PRC). In contrast to deletion or truncating mutations seen in other tumors, BCOR expression is upregulated in CNS-BCOR ITD, and a distinct oncogenic mechanism has been suggested. However, the effects of this change on the biology of neuroepithelial cells is poorly understood. In this study, we introduced either wildtype BCOR or BCOR-ITD into human and murine neural stem cells and analyzed them with quantitative RT-PCR and RNA-sequencing, as well as growth, clonogenicity, and invasion assays. In human cells, BCOR-ITD promoted derepression of PRC2-target genes compared to wildtype BCOR. A similar effect was found in clinical specimens from previous studies. However, no growth advantage was seen in the human neural stem cells expressing BCOR-ITD, and long-term models could not be established. In the murine cells, both wildtype BCOR and BCOR-ITD overexpression affected cellular differentiation and histone methylation, but only BCOR-ITD increased cellular growth, invasion, and migration. BCOR-ITD overexpression drives transcriptional changes, possibly due to altered PRC function, and contributes to the oncogenic transformation of neural precursors.

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Effect of stiffness change of transplanted induced neural stem cells after spinal cord injury using silk hydrogel

Journal of the Neurological Sciences ◽

10.1016/j.jns.2017.08.815 ◽

2017 ◽

Vol 381 ◽

pp. 286

Author(s):

G. Davaa ◽

J.Y. Hong ◽

J. Olmos Buitrago ◽

H.W. Kim ◽

J.K. Hyun

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Neural Stem Cells ◽

Cord Injury ◽

Induced Neural Stem Cells ◽

Silk Hydrogel

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Immunosuppressants Affect Human Neural Stem Cells In Vitro but Not in an In Vivo Model of Spinal Cord Injury

Stem Cells Translational Medicine ◽

10.5966/sctm.2012-0175 ◽

2013 ◽

Vol 2 (10) ◽

pp. 731-744 ◽

Cited By ~ 21

Author(s):

Christopher J. Sontag ◽

Hal X. Nguyen ◽

Noriko Kamei ◽

Nobuko Uchida ◽

Aileen J. Anderson ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Neural Stem Cells ◽

In Vivo Model ◽

Human Neural Stem Cells ◽

Cord Injury

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Targeted Treatment of Experimental Spinal Cord Glioma With Dual Gene-Engineered Human Neural Stem Cells

Neurosurgery ◽

10.1227/neu.0000000000001174 ◽

2015 ◽

Vol 79 (3) ◽

pp. 481-491 ◽

Cited By ~ 11

Author(s):

Alexander E. Ropper ◽

Xiang Zeng ◽

Hariprakash Haragopal ◽

Jamie E. Anderson ◽

Zaid Aljuboori ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Growth Rate ◽

Neural Stem Cells ◽

Tumor Growth ◽

Rat Model ◽

Weight Bearing ◽

Tumor Growth Rate ◽

Intramedullary Spinal Cord ◽

Human Neural Stem Cells

Abstract BACKGROUND There are currently no satisfactory treatments or experimental models showing autonomic dysfunction for intramedullary spinal cord gliomas (ISCG). OBJECTIVE To develop a rat model of ISCG and investigate whether genetically engineered human neural stem cells (F3.hNSCs) could be developed into effective therapies for ISCG. METHODS Immunodeficient/Rowett Nude rats received C6 implantation of G55 human glioblastoma cells (10K/each). F3.hNSCs engineered to express either cytosine deaminase gene only (i.e., F3.CD) or dual genes of CD and thymidine kinase (i.e., F3.CD-TK) converted benign 5-fluorocytosine and ganciclovir into oncolytic 5-fluorouracil and ganciclovir-triphosphate, respectively. ISCG rats received injection of F3.CD-TK, F3.CD, or F3.CD-TK debris near the tumor epicenter 7 days after G55 seeding, followed with 5-FC (500 mg/kg/5 mL) and ganciclovir administrations (25 mg/kg/1 mL/day × 5/each repeat, intraperitoneal injection). Per humane standards for animals, loss of weight-bearing stepping in the hindlimb was used to determine post-tumor survival. Also evaluated were autonomic functions and tumor growth rate in vivo. RESULTS ISCG rats with F3.CD-TK treatment survived significantly longer (37.5 ± 4.78 days) than those receiving F3.CD (21.5 ± 1.75 days) or F3.CD-TK debris (19.3 ± 0.85 days; n = 4/group; P <.05, median rank test), with significantly improved autonomic function and reduced tumor growth rate. F3.DC-TK cells migrated diffusively into ISCG clusters to mediate oncolytic effect. CONCLUSION Dual gene-engineered human neural stem cell regimen markedly prolonged survival in a rat model that emulates somatomotor and autonomic dysfunctions of human cervical ISCG. F3.CD-TK may provide a novel approach to treating clinical ISCG.

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