Neural Stem Cells Enhance Nerve Regeneration after Sciatic Nerve Injury in Rats

Abstract

With the development of tissue engineering and the shortage of autologous nerve grafts in nerve reconstruction, cell transplantation in a conduit is an alternative strategy to improve nerve regeneration. The present study evaluated the effects and mechanism of brain-derived neural stem cells (NSCs) on sciatic nerve injury in rats. At the transection of the sciatic nerve, a 10-mm gap between the nerve stumps was bridged with a silicon conduit filled with 5 × 10(5) NSCs. In control experiments, the conduit was filled with nerve growth factor (NGF) or normal saline (NS). The functional and morphological properties of regenerated nerves were investigated, and expression of hepatocyte growth factor (HGF) and NGF was measured. One week later, there was no connection through the conduit. Four or eight weeks later, fibrous connections were evident between the proximal and distal segments. Motor function was revealed by measurement of the sciatic functional index (SFI) and sciatic nerve conduction velocity (NCV). Functional recovery in the NSC and NGF groups was significantly more advanced than that in the NS group. NSCs showed significant improvement in axon myelination of the regenerated nerves. Expression of NGF and HGF in the injured sciatic nerve was significantly lower in the NS group than in the NSCs and NGF groups. These results and other advantages of NSCs, such as ease of harvest and relative abundance, suggest that NSCs could be used clinically to enhance peripheral nerve repair.

The Inorganic Side of NGF: Copper(II) and Zinc(II) Affect the NGF Mimicking Signaling of the N-Terminus Peptides Encompassing the Recognition Domain of TrkA Receptor

“…NGF, composed of 118 amino acid residues (Angeletti et al, 1971) has been discovered in the 1950s (Levi-Montalcini and Hamburger, 1951; Levi-Montalcini, 1952; Cohen et al, 1954; Levi-Montalcini and Booker, 1960); it displays multiple physiological actions in the central nervous system, showing neurotrophic effects and resulting critical for the neurite outgrowth and survival and maintenance of neurons (Hu et al, 2005; Tucker et al, 2008; Xu et al, 2012). …”

Long-Term Efficacy and Safety Outcomes of Transplantation of Induced Pluripotent Stem Cell-Derived Neurospheres with Bioabsorbable Nerve Conduits for Peripheral Nerve Regeneration in Mice

“…To date, several methods have been developed to improve the efficacy of nerve conduits by accelerating nerve regeneration and bridging longer nerve gaps [Johnson et al, 2013;Carriel et al, 2014;Li et al, 2014]. In particular, transplantation of supportive cells such as Schwann cells, neural crest stem cells and bone marrowderived mesenchymal stem cells within nerve conduits enhances the repair of long nerve defects [Mosahebi et al, 2002;Xu et al, 2012;Hsu et al, 2013;Hu et al, 2013;Li et al, 2014]. The induced pluripotent stem cell (iPSc) represents an attractive source of cells that are potentially useful for nerve conduit support [Takahashi and Yamanaka, 2006;Xu et al, 2011].…”

The Nerve Growth Factor Signaling and Its Potential as Therapeutic Target for Glaucoma

“…NGF possesses neurotrophic effects and is critical for the neurite outgrowth and survival and maintenance of neurons. Studies, in vitro and in vivo , have shown that NGF stimulates neurite outgrowth and axonal branching and extension [18–20]. Most importantly, NGF has strong antiapoptotic effect and, with deprivation of NGF, neurons exhibit a series of morphological changes and eventually undergo apoptosis [21].…”

“…PI3K is activated and recruited to the plasma membrane and leads to the production of phosphoinositide 3,4,5-trisphosphate and membrane translocation of the serine/threonine-protein kinases Akt and Akt activation [20]. Although there are other downstream targets of PI3K, the PI3K/Akt signaling pathway is particularly important for neuronal survival and the synthesis of many new cellular proteins.…”