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Remyelination improvement after neurotrophic factors secreting cells transplantation in rat spinal cord injury.

ABSTRACT: Neurotrophic factors secreting cells (NTS-SCs) may be a superior cell source for cell-based therapy in neurodegenerative diseases. NTS-SCs are able to secrete some neurotrophic Such as nerve growth factor and glia-derived neurotrophic factor. Our primary aim was to assess transplantation of neurotrophic factor secreting cells derived from human adipose-derived stem cells (hADSCs) into the damaged spinal cord rats and determine the potential of these cells in remyelination.To this end, 40 adult male Wistar rats were categorized into four groups including; control, lysolecithin (Lysophosphatidylcholines or LPC), vehicle, and NTS-SCs transplan-tation. Local demyelination was induced using LPC injection into the lateral column of spinal cord. Seven days after the lysolecithin lesion, the cells transplantation was performed. The ultrastructure of myelinated fibers was examined with a transmission electron microscope to determine the extent of myelin destruction and remyelinization 4 weeks post cell transplantation. Moreover, the presence of oligodendrocyte in the lesion of spinal cord was assessed by immunohistochemistry procedure.The results of current study indicated that in NTF-SCs transplantation group, the remyelination process and the mean of myelin sheath thickness as well as axonal diameters were significantly higher than other groups (P<0.001). Furthermore, immunohistochemistry analysis revealed that in NTF-SCs transplantation group more than 10 percent of transplanted cells were positive for specific markers of oligodendrocyte cells.NTF-SCs transplantation represents a valuable option for cell-based therapy in the nervous tissue damages.

SUBMITTER: Razavi S

PROVIDER: S-EPMC5425921 | biostudies-other | 2017 Apr

REPOSITORIES: biostudies-other

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Project description:Unlabelled: 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.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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Remyelination improvement after neurotrophic factors secreting cells transplantation in rat spinal cord injury.

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