Topical Application of Human Wharton’s Jelly Mesenchymal Stem Cells Accelerates Mouse Sciatic Nerve Recovery and is Associated with Upregulated Neurotrophic Factor Expression

Abstract

Peripheral nerve regeneration following injury is often slow and impaired, which results in weakened and denervated muscle with subsequent atrophy. Human Wharton’s jelly mesenchymal stem cells (hWJ-MSC) have potential regenerative properties which, however, remain unknown in mouse nerve recovery. This study investigated the effect of the topical application of hWJ-MSC onto repairing transected sciatic nerves in a mouse model. Human adipocyte-derived stem cells (hADSC) were used as a positive control. The sciatic nerve of BALB/c mice was transected at a fixed point and repaired under the microscope using 10-0 sutures. hWJ-MSC and hADSC were applied to the site of repair and mice were followed up for 1 year. The hWJ-MSC group had significantly better functional recovery of five-toe spread and gait angles compared with the negative control and hADSC groups. hWJ-MSC improved sciatic nerve regeneration in a dose-dependent fashion. The hWJ-MSC group had a better quality of regenerated nerve with an increased number of myelinated axons throughout. hWJ-MSC appear to be safe in mice after 1 year of follow-up. hWJ-MSC also expressed higher levels of neurotrophic factor-3, brain-derived neurotrophic factor, and glial-derived neurotrophic factor than hADSC. hWJ-MSC may promote better nerve recovery than hADSC because of this upregulation of neurotrophic factors.

Human Wharton’s Jelly Mesenchymal Stem Cell-Mediated Sciatic Nerve Recovery Is Associated with the Upregulation of Regulatory T Cells

“…Our previous study demonstrated that the topical application of hWJ-MSC accelerates signs of sciatic nerve recovery, such as five-toe spread and toe-off phase, partly via the direct upregulation and release of neurotrophic factors ( Supplementary Figure S1A,B ) [ 10 ]. To investigate the immunomodulatory effects of hWJ-MSC on sciatic nerve recovery, various immune cell populations were analyzed after hWJ-MSC administration to the nerve coaptation site.…”

“…MSC can be isolated from Wharton’s jelly from the umbilical cord, which contains mucoid connective tissue and fibroblast-like cells. Our previous study demonstrated that the topical application of human Wharton’s jelly-derived MSC (hWJ-MSC) promote sciatic nerve recovery and regeneration because of the direct upregulation and release of neurotrophic factors [ 10 ]. MSC also exhibit diverse immunomodulatory effects, in addition to their regenerative property [ 11 , 12 ].…”

Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities

“…Five-toe spread analysis represents the intrinsic muscle recovery and indicates the signal transmission recovery after nerve transection [ 9 , 11 , 12 ]. In the present study, the distance of the five-toe spread was estimated in each mouse before the nerve transection.…”

“…Nerve injuries far from end-target organs, such as muscles, need a much longer time to regenerate, resulting in the atrophy of motor end-plates and muscles [ 7 ]. New strategies are being developed in a great deal of research for the improvement of peripheral nerve regeneration, which ameliorates the outcomes following nerve injury [ 8 , 9 , 10 , 11 , 12 ].…”

Gastrodin promotes the regeneration of peripheral nerves by regulating miR-497/BDNF axis

“…Schwann cell (SC), is the main glial cell in PNS, and it is pivotal in regulating the regeneration of peripheral nerves [ 4 , 5 ]. Reportedly, SCs can produce and secrete nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which are implicated in the post-PNI growth and regeneration processes of peripheral nerve [ 6 – 10 ]. Promoting the multiplication and migration of SCs can improve the regeneration of peripheral nerves [ 11 , 12 ].…”