Transplantation of embryonic spinal cord neurons to the injured distal nerve promotes axonal regeneration after delayed nerve repair

In peripheral nerve injuries (PNIs) in which proximal axons do not regenerate quickly enough, significant chronic degeneration of Schwann cells (SCs) can occur at the distal stump of the injured nerve and obstruct regeneration. Cell transplantation can delay the degeneration of SCs, but transplanted cells fail to generate voluntary electrical impulses without downstream signal stimulation from the central nervous system. In this study, we combined cell transplantation and nerve transfer strategies to investigate whether the transplantation of embryonic spinal cord cells could benefit the microenvironment of the distal stump of the injured nerve. The experiment consisted of two stages. In the first-stage surgery, common peroneal nerves were transected, and embryonic day 14 (E14) cells or cell culture medium was transplanted into the distal stump of the CPs. Six months after the first-stage surgery, the transplanted cells were removed, and the nerve segment distal to the transplanted site was used to bridge freshly cut tibial nerves to detect whether the cell-treated graft promoted axon growth. The phenotypic changes and the neurotrophic factor expression pattern of SCs distal to the transplanted site were detected at several time points after cell transplantation and excision. The results showed that at different times after transplantation, the cells could survive and generate neurons. Thus, the neurons play the role of proximal axons to prevent chronic degeneration and fibrosis of SCs. After excision of the transplanted cells, the SCs returned to their dedifferentiated phenotype and upregulated growth-associated gene expression. The ability of SCs to be activated again allowed a favorable microenvironment to be created and enhanced the regeneration and remyelination of proximal axons. Muscle reinnervation was also elevated. This transplantation strategy could provide a treatment option for complex neurological injuries in the clinic.

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Retinoic acid as a chemoattractant for cultured embryonic spinal cord neurons of the African Clawed Frog, Xenopus laevis

Canadian Journal of Zoology ◽

10.1139/cjz-2016-0279 ◽

2017 ◽

Vol 95 (9) ◽

pp. 653-661 ◽

Cited By ~ 2

Author(s):

C.D. Rand ◽

G.E. Spencer ◽

R.L. Carlone

Keyword(s):

Spinal Cord ◽

Retinoic Acid ◽

Xenopus Laevis ◽

Neurite Outgrowth ◽

Growth Cone ◽

Receptor Subtype ◽

Spinal Cord Neurons ◽

African Clawed Frog ◽

Embryonic Spinal Cord ◽

Clawed Frog

Retinoic acid (RA), an active metabolite of vitamin A, is important for neural development and regeneration and can induce neurite outgrowth. It may also act as a guidance molecule by attracting neurite processes during outgrowth. In the African Clawed Frog (Xenopus laevis (Daudin, 1802)), RA has been shown to play an important role in the development of the anterior–posterior axis. However, whether RA can act as a trophic or tropic molecule on embryonic neurons of this species has not been determined. In this study, we investigated the effects of two retinoid isomers, all-trans retinoic acid (atRA) and 9-cis retinoic acid (9-cisRA), on cultured embryonic spinal cord neurons of X. laevis. Both isomers significantly enhanced neurite outgrowth compared with the vehicle control. In addition, atRA induced growth cone turning, which was blocked with a retinoic acid receptor (RAR) antagonist, selective for the β receptor subtype. Immunostaining also revealed RAR immunoreactivity in the neurites and growth cones of these cells. Interestingly, the 9-cisRA isomer also induced significant growth cone turning and this response was inhibited by a retinoid X receptor (RXR) pan-antagonist. Overall, we have provided evidence for both trophic and chemotropic actions of two naturally occurring retinoid isomers on Xenopus embryonic spinal cord neurons in culture.

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Ex vivo infection of human embryonic spinal cord neurons prior to transplantation into adult mouse cord

BMC Neuroscience ◽

10.1186/1471-2202-11-65 ◽

2010 ◽

Vol 11 (1) ◽

pp. 65

Author(s):

Gábor Márton ◽

Dóra Tombácz ◽

Judit S Tóth ◽

András Szabó ◽

Zsolt Boldogköi ◽

...

Keyword(s):

Spinal Cord ◽

Adult Mouse ◽

Ex Vivo ◽

Spinal Cord Neurons ◽

Embryonic Spinal Cord

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A New Resorbable Wrap-Around Implant as an Alternative Nerve Repair Technique

Journal of Hand Surgery (European Volume) ◽

10.1054/jhsb.1998.0001 ◽

1999 ◽

Vol 24 (3) ◽

pp. 291-295 ◽

Cited By ~ 69

Author(s):

A. HAZARI ◽

G. JOHANSSON-RUDÉN ◽

K. JUNEMO-BOSTROM ◽

C. LJUNGBERG ◽

G. TERENGHI ◽

...

Keyword(s):

Axonal Regeneration ◽

Nerve Repair ◽

Axon Diameter ◽

Contralateral Limb ◽

Repair Technique ◽

Significant Difference ◽

Myelin Thickness ◽

Distal Nerve ◽

Adult Cats ◽

G Ratio

Poly-3-hydroxybutyrate (PHB), a bacterial storage product, is available as bioabsorbable sheets and has been used in this study for primary nerve repair. The aim was to assess axonal regeneration following such repair and determine the inflammatory response to PHB. In 20 adult cats, the transected superficial radial nerve was wrapped in PHB sheets, while primary epineural repair was carried out in the contralateral limb. At 6 and 12 months, the repair sites were assessed immunohistochemically for macrophage infiltration and myelinated axons were counted in the distal nerve. Mean macrophage counts across the whole width of the nerve in both groups at 6 and 12 months showed no statistically significant difference. Nor was there any significant difference between the two groups at both time-points in axon counts, axon diameter, myelin thickness and g-ratio. There was a statistically significant increase in fibre diameters at 12 months, indicating that fibres were undergoing continuous maturation.

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