It is reported that neural stem cells (NSC) can arrest denervated muscle atrophy and promote nerve regeneration when transplanted into injured peripheral nerves, and that regenerated host axons can form synapses with transplanted and differentiated NSC. In this study, F344 rat nerve segments and F344 rat NSC were transplanted into host green fluorescence protein (GFP) transgenic F344 rats. This allowed transplanted F344 rat tissue to be used as a non-luminous background for the clear visualization of regenerated host GFP axons. Regenerated host axons grew into the transplanted F344 nerve segment 2 weeks after nerve anastomosis. Immunohistochemical staining and confocal microscope analysis revealed that regenerated host axons formed synapses with NSC-derived neurons. The findings confirmed that regenerated peripheral axons form synapses with neurons in peripheral nerves, possibly forming the basis for clinical application in peripheral nerve injury.
LundborgG: A 25-year perspective of peripheral nerve surgery: Evolving neuroscientific concepts and clinical significance. J Hand Surg2000; 25: 391–414.
2.
ReynoldsBATetzlaffWWeissS: A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci1992; 12: 4565–4574.
3.
LeeJPJeyakumarMGonzalezR: Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease. Nat Med2007; 13: 439–447.
XiaoMKlueberKMGuoZ: Human adult olfactory neural progenitors promote axotomized rubrospinal tract axonal reinnervation and locomotor recovery. Neurobiol Dis2007; 26: 363–374.
6.
GaoJCoggeshallRETarasenkoYI: Human neural stem cell-derived cholinergic neurons innervate muscle in motoneuron deficient adult rats. Neuroscience2005; 131: 257–262.
7.
MacDonaldSCFleetwoodIGHochmanS: Functional motor neurons differentiating from mouse multipotent spinal cord precursor cells in culture and after transplantation into transected sciatic nerve. J Neurosurg2003; 98: 1094–1103.
8.
MilesGBYohnDCWichterleH: Functional properties of motoneurons derived from mouse embryonic stem cells. J Neurosci2004; 24: 7848–7858.
9.
LiXJDuZWZarnowskaED: Specification of motoneurons from human embryonic stem cells. Nat Biotechnol2005; 23: 215–221.
WatanabeHOchiyaTUedaS: Differentiation of a hepatic phenotype after heterotropic transplantation of heart, kidney, brain, and skin tissues into liver in F344 rats. Biochem Biophys Res Commun2007; 354: 841–845.
12.
ZimmermannM: Ethical guidelines for investigations of experimental pain in conscious animals. Pain1983; 16: 109–110.
13.
ReynoldsBAWeissS: Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science1992; 255: 1707–1710.
14.
GaoJCoggeshallREChungJM: Functional motoneurons develop from human neural stem cell transplants in adult rats. Neuroreport2007; 18: 565–569.
15.
LinWBurgessRWDominguezB: Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. Nature2001; 410: 1057–1064.
16.
VlastarakosPVNikolopoulosTPTavoulariE: Sensory cell regeneration and stem cells: What we have already achieved in the management of deafness. Otol Neurotol2008; 29: 758–768.
17.
MatsumotoMNakagawaTHigashiT: Innervation of stem cell-derived neurons into auditory epithelia of mice. Neuroreport2005; 16: 787–790.
18.
ShiFCorralesCELibermanMC: BMP4 induction of sensory neurons from human embryonic stem cells and reinnervation of sensory epithelium. Eur J Neurosci2007; 26: 3016–3023.
19.
TodaHTakahashiJMizoguchiA: Neurons generated from adult rat hippocampal stem cells form functional glutamatergic and GABAergic synapses in vitro. Exp Neurol2000; 165: 66–76.
20.
CummingsBJUchidaNTamakiSJ: Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. Proc Natl Acad Sci USA2005; 102: 14069–14074.
21.
KatsukiMAtsutaYHirayamaT: Reinnervation of denervated muscle by transplantation of fetal spinal cord to transected sciatic nerve in the rat. Brain Res1997; 771: 31–36.
22.
ErbDEMoraRJBungeRP: Reinnervation of adult rat gastrocnemius muscle by embryonic motoneurons transplanted into the axotomized tibial nerve. Exp Neurol1993; 124: 372–376.
23.
LladoJHaenggeliCMaragakisNJ: Neural stem cells protect against glutamate-induced excitotoxicity and promote survival of injured motor neurons through the secretion of neurotrophic factors. Mol Cell Neurosci2004; 27: 322–331.
