Genetically modified mesenchymal stem cells (MSCs) promote axonal regeneration and prevent hypersensitivity after spinal cord injury

Kumagai, Gentaro; Tsoulfas, Pantelis; Toh, Satoshi; McNiece, Ian; Bramlett, Helen M.; Dietrich, W. Dalton

doi:10.1016/j.expneurol.2013.06.028

Cited by 66 publications

(54 citation statements)

References 78 publications

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“…Boido and coworkers injected MSCs intralesionally immediately after SCI and did not find differences in number and macroscopic appearance of microglial cells at a later stage (day 26 post lesion), despite improved clinical outcome: however the authors did not evaluate the phenotype of the cells (beneficial vs. detrimental) [104]. A reduced number of activated microglial/macrophages, as measured by count of CD68-positive cells, at six weeks post injury was found in spinal cord of rats treated with MSCs at day 7 post injury; similar results were obtained with MSCs genetically engineered to express multineurotrophin MNTS1, a neurotrophin, but the treatment was associated with improved axonal growth and sensory function, suggesting the possibility that MNTS1 shuttled by MSCs can improve neural repair [105].…”

Section: Spinal Cord Injurysupporting

confidence: 78%

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

2015

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Section: Spinal Cord Injurysupporting

confidence: 78%

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

2015

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“…Transplantation of stem cells into the lesion cavity, post-SCI, has long been demonstrated to promote the growth of axons into the graft (Kumagai et al, 2013;Lu, Jones, & Tuszynski, 2005;Neuhuber, Timothy Himes, Shumsky, Gallo, & Fischer, 2005). The present study demonstrated that overexpressing SDF-1␣ in MSCs can enhance the existence of GAP-43-positive axons inside the area of the lesion at a higher level than MSCs alone can provide.…”

Section: An Stewart Et Al / Sdf-1 Overexpression By Mesenchymal Stmentioning

confidence: 51%

“…MSCs (Kumagai et al, 2013;Lu et al, 2005) and, as shown in this study, axonal growth can be enhanced through modifying the secretome by overexpressing chemo-attractants, such as SDF-1␣. Due to the role of GAP-43 in the growth cone of developing or regenerating axons, it may also be likely that the effects observed in this study point towards a longer and more sustained growth response, due to the presence of MSCs that overexpress SDF-1␣.…”

Section: An Stewart Et Al / Sdf-1 Overexpression By Mesenchymal Stmentioning

confidence: 96%

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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“…Genetically modified stem cells can not only replace the damaged neural cells, but also overexpress specific neurotropic factors to rebuild the neural circuit in the spinal cord (Kumagai et al, 2013;Castellanos et al, 2002;Lin et al, 2013). It is possible that after figuring out the genetic characteristics of some animals that can achieve complete spinal cord regeneration after injury, zebra fish for example, the genes necessary for neural regeneration after SCI can be transferred to the injury site to promote the axonal regeneration and functional recovery.…”

Section: Stem Cell Therapy Combined With Gene Therapymentioning

confidence: 98%

Stem cell based therapies for spinal cord injury

Muheremu

Jiang²,

2016

Tissue and Cell

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Genetically modified mesenchymal stem cells (MSCs) promote axonal regeneration and prevent hypersensitivity after spinal cord injury

Cited by 66 publications

References 78 publications

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

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

Stem cell based therapies for spinal cord injury

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