Neurotrophin-3 gene modified mesenchymal stem cells promote remyelination and functional recovery in the demyelinated spinal cord of rats

Zhang, Yu Jiao; Zhang, Wei; Lin, Cheng; Ding, Ying; Huang, Si Fan; Wu, Jin Lang; Li, Yan; Dong, Hongxin; Zeng, Yuan

doi:10.1016/j.jns.2011.09.027

Cited by 39 publications

(33 citation statements)

References 39 publications

(72 reference statements)

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“…The trophic factors released from MSCs, in addition to the growth-sustaining extracellular matrix provided by the transplant, may also be capable of promoting regeneration of axons into, or beyond, the scar tissue produced by the injury (Kadoya et al, 2009). The identification of the ability for MSCs to secrete trophic factors as a mechanism to support recovery has led to the initiation of studies that utilize genetic engineering of MSCs to enhance the release of important molecules in attempts to further mitigate secondary injury cascades and promote cellular survival (Crane, Rossignol, & Dunbar, 2014;Dey et al, 2010;Ruitenberg et al, 2005;Sasaki et al, 2009;Shang et al, 2011;Zhang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

SDF-1 overexpression by mesenchymal stem cells enhances GAP-43-positive axonal growth following spinal cord injury

Stewart

Matyas

Welchko

et al. 2017

RNN

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Abstract.Purpose: Utilizing genetic overexpression of trophic molecules in cell populations has been a promising strategy to develop cell replacement therapies for spinal cord injury (SCI). Over-expressing the chemokine, stromal derived factor-1 (SDF-1␣), which has chemotactic effects on many cells of the nervous system, offers a promising strategy to promote axonal regrowth following SCI. The purpose of this study was to explore the effects of human SDF-1␣, when overexpressed by mesenchymal stem cells (MSCs), on axonal growth and motor behavior in a contusive rat model of SCI. Methods: Using a transwell migration assay, the paracrine effects of MSCs, which were engineered to secrete human SDF-1␣ (SDF-1-MSCs), were assessed on cultured neural stem cells (NSCs). For in vivo analyses, the SDF-1-MSCs, unaltered MSCs, or Hanks Buffered Saline Solution (vehicle) were injected into the lesion epicenter of rats at 9-days post-SCI. Behavior was analyzed for 7-weeks post-injury, using the Basso, Beattie, and Bresnahan (BBB) scale of locomotor functions. Immunohistochemistry was performed to evaluate major histopathological outcomes, including gliosis, inflammation, white matter sparing, and cavitation. New axonal outgrowth was characterized using immunohistochemistry against the neuron specific growth-associated protein-43 (GAP-43). Results:The results of these experiments demonstrate that the overexpression of SDF-1␣ by MSCs can enhance the migration of NSCs in vitro. Although only modest functional improvements were observed following transplantation of SDF-1-MSCs, a significant reduction in cavitation surrounding the lesion, and an increased density of GAP-43-positive axons inside the SCI lesion/graft site were found. Conclusion:The results from these experiments support the potential role for utilizing SDF-1␣ as a treatment for enhancing growth and regeneration of axons after traumatic SCI. Research HighlightsMSCs were engineered to overexpress SDF-1␣. SDF-1␣ expression by MSCs enhances the migration of NSCs in vitro. SDF-1␣ expression by MSCs enhanced GAP-43 fibers within the lesion center.

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Section: Introductionmentioning

confidence: 99%

SDF-1 overexpression by mesenchymal stem cells enhances GAP-43-positive axonal growth following spinal cord injury

Stewart

Matyas

Welchko

et al. 2017

RNN

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“…7 Stem cell transplantation is a promising candidate to treat SCI. [8][9][10][11][12] Recent work showed that stem cells, such as mesenchymal stem cells (MSCs), [13][14][15] neural stem/progenitor cells (NS/ PCs), 16,17 and embryonic stem cells (ESCs), [18][19][20] have immunoregulatory capacity and anti-inflammatory effects and could enhance functional improvement through inducing macrophages M1/M2 phenotype transformation post SCI. This review will discuss 1) the general feature of macrophages in response to SCI, 2) the phenotype and function of macrophages in SCI, and 3) the effects of stem cells on macrophage polarization and its role in stem cell-based therapies for SCI.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effect of stem cells against spinal cord injury via regulating macrophage polarization

Zhang¹,

He²

2017

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Spinal cord injury (SCI) is a traumatic event that involves not just an acute physical injury but also inflammation-driven secondary injury. Macrophages play a very important role in secondary injury. The effects of macrophages on tissue damage and repair after SCI are related to macrophage polarization. Stem cell transplantation has been studied as a promising treatment for SCI. Recently, increasing evidence shows that stem cells, including mesenchymal stem, neural stem/progenitor, and embryonic stem cells, have an anti-inflammatory capacity and promote functional recovery after SCI by inducing macrophages M1/M2 phenotype transformation. In this review, we will discuss the role of stem cells on macrophage polarization and its role in stem cell-based therapies for SCI.

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“…Loss of oligodendrocytes and myelin results in severe functional impairment [33,34]. Some studies also support the key role of remyelination in promoting neuronal survival after adult CNS injury [35,36].…”

Section: Discussionmentioning

confidence: 89%

Graft of a Tissue-Engineered Neural Scaffold Serves as a Promising Strategy to Restore Myelination after Rat Spinal Cord Transection

Lai

Wang²,

Ling³

et al. 2014

Stem Cells and Development

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Remyelination remains a challenging issue in spinal cord injury (SCI). In the present study, we cocultured Schwann cells (SCs) and neural stem cells (NSCs) with overexpression of neurotrophin-3 (NT-3) and its high affinity receptor tyrosine kinase receptor type 3 (TrkC), respectively, in a gelatin sponge (GS) scaffold. This was aimed to generate a tissue-engineered neural scaffold and to investigate whether it could enhance myelination after a complete T10 spinal cord transection in adult rats. Indeed, many NT-3 overexpressing SCs (NT-3-SCs) in the GS scaffold assumed the formation of myelin. More strikingly, a higher incidence of NSCs overexpressing TrkC differentiating toward myelinating cells was induced by NT-3-SCs. By transmission electron microscopy, the myelin sheath showed distinct multilayered lamellae formed by the seeded cells. Eighth week after the scaffold was transplanted, some myelin basic protein (MBP)-positive processes were observed within the transplantation area. Remarkably, certain segments of myelin derived from NSC-derived myelinating cells and NT-3-SCs were found to ensheath axons. In conclusion, we show here that transplantation of the GS scaffold promotes exogenous NSC-derived myelinating cells and SCs to form myelins in the injury/transplantation area of spinal cord. These findings thus provide a neurohistological basis for the future application or transplantation using GS neural scaffold to repair SCI.

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Neurotrophin-3 gene modified mesenchymal stem cells promote remyelination and functional recovery in the demyelinated spinal cord of rats

Cited by 39 publications

References 39 publications

SDF-1 overexpression by mesenchymal stem cells enhances GAP-43-positive axonal growth following spinal cord injury

SDF-1 overexpression by mesenchymal stem cells enhances GAP-43-positive axonal growth following spinal cord injury

Anti-inflammatory effect of stem cells against spinal cord injury via regulating macrophage polarization

Graft of a Tissue-Engineered Neural Scaffold Serves as a Promising Strategy to Restore Myelination after Rat Spinal Cord Transection

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