Hu, Z, Ulfendahl, M and Olivius, NP. NGF stimulates extensive neurite outgrowth from implanted dorsal root ganglion neurons following transplantation into the adult rat inner ear. Neurobiol Dis 18: 184-192

Center for Hearing and Communication Research, Karolinska Institute, SE-171 76 Stockholm, Sweden.
Neurobiology of Disease (Impact Factor: 5.08). 03/2005; 18(1):184-92. DOI: 10.1016/j.nbd.2004.09.010
Source: PubMed


Neuronal tissue transplantation is a potential way to replace degenerated spiral ganglion neurons (SGNs) since these cells cannot regenerate in adult mammals. To investigate whether nerve growth factor (NGF) can stimulate neurite outgrowth from implanted neurons, mouse embryonic dorsal root ganglion (DRG) cells expressing enhanced green fluorescent protein (EGFP) were transplanted into the scala tympani of adult rats with a supplement of NGF or artificial perilymph. DRG neurons were observed in the cochlea for up to 6 weeks postoperatively. A significant difference was identified in the number of DRG neurons between the NGF and non-NGF groups. In the NGF group, extensive neurite projections from DRGs were found penetrating the osseous modiolus towards the spiral ganglion. These results suggest the possibility that embryonic neuronal implants may become integrated within the adult auditory nervous system. In combination with a cochlear prosthesis, a neuronal implantation strategy may provide a possibility for further treatment of profoundly deaf patients.

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    • "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] [19] [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]. "
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    ABSTRACT: Neuroprotective therapies which focus on factors leading to retinal ganglion cells (RGCs) degeneration have been drawing more and more attention. The beneficial effects of nerve growth factor (NGF) on the glaucoma have been recently suggested, but its effects on eye tissue are complex and controversial in various studies. Recent clinical trials of systemically and topically administrated NGF demonstrate that NGF is effective in treating several ocular diseases, including glaucoma. NGF has two receptors named high affinity NGF tyrosine kinase receptor TrkA and low affinity receptor p75NTR. Both receptors exist in cells in retina like RGC (expressing TrkA) and glia cells (expressing p75NTR). NGF functions by binding to TrkA or p75NTR alone or both together. The binding of NGF to TrkA alone in RGC promotes RGC's survival and proliferation through activation of TrkA and several prosurvival pathways. In contrast, the binding of NGF to p75NTR leads to apoptosis although it also promotes survival in some cases. Binding of NGF to both TrkA and p75NTR at the same time leads to survival in which p75NTR functions as a TrkA helping receptor. This review discusses the current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma.
    BioMed Research International 08/2014; 2014:759473. DOI:10.1155/2014/759473 · 2.71 Impact Factor
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    • "Their ability to integrate into the ear and respond to the denervated cochlear environment suggests that the neural progenitors that we used were at a developmental stage that retained the plasticity to respond to these potential signals from the immediate environment. These cells are more likely to be responsive to cues in the host ear than differentiated neurons (Hu et al., 2005a) that did not grow neurites toward hair cells when transplanted into the inner ear and neural stem cells that did not show evidence of neurite outgrowth toward the hair cells in the inner ear of guinea pigs (Hu et al., 2005b). The cues guiding axon growth might also be interpreted best by progenitor cells rather than mature neurons since molecules that guide axon growth by binding to receptors on growth cones are expressed in the embryo (Brors et al., 2003;Tessarollo et al., 2004). "
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    ABSTRACT: Hearing loss in mammals is irreversible because cochlear neurons and hair cells do not regenerate. To determine whether we could replace neurons lost to primary neuronal degeneration, we injected EYFP-expressing embryonic stem cell-derived mouse neural progenitor cells into the cochlear nerve trunk in immunosuppressed animals 1 week after destroying the cochlear nerve (spiral ganglion) cells while leaving hair cells intact by ouabain application to the round window at the base of the cochlea in gerbils. At 3 days post transplantation, small grafts were seen that expressed endogenous EYFP and could be immunolabeled for neuron-specific markers. Twelve days after transplantation, the grafts had neurons that extended processes from the nerve core toward the denervated organ of Corti. By 64-98 days, the grafts had sent out abundant processes that occupied a significant portion of the space formerly occupied by the cochlear nerve. The neurites grew in fasciculating bundles projecting through Rosenthal's canal, the former site of spiral ganglion cells, into the osseous spiral lamina and ultimately into the organ of Corti, where they contacted hair cells. Neuronal counts showed a significant increase in neuronal processes near the sensory epithelium, compared to animals that were denervated without subsequent stem cell transplantation. The regeneration of these neurons shows that neurons differentiated from stem cells have the capacity to grow to a specific target in an animal model of neuronal degeneration.
    Journal of Neurobiology 11/2006; 66(13):1489-500. DOI:10.1002/neu.20310 · 3.84 Impact Factor
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    • "In future studies, we should select appropriate cells with or without some adjunct therapies such as pre-conditioning with neurotrophic factors. It might be beneficial to add some neurotrophic factors such as NGF to foster neurite outgrowth from the cells transplanted to the injured auditory nerve (Hu et al., 2005). "
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    ABSTRACT: We have developed a technique to deliver cells to the inner ear without injuring the membranes that seal the endolymphatic and perilymphatic chambers. The integrity of these membranes is essential for normal hearing, and the technique should significantly reduce surgical trauma during cell transplantation. Embryonic stem cells transplanted at the internal auditory meatal portion of an atrophic auditory nerve migrated extensively along it. Four-five weeks after transplantation, the cells were found not only throughout the auditory nerve, but also in Rosenthal's canal and the scala media, the most distal portion of the auditory nervous system where the hair cells reside. Migration of the transplanted cells was more extensive following damage to the auditory nerve. In the undamaged nerve, migration was more limited, but the cells showed more signs of neuronal differentiation. This highlights an important balance between tissue damage and the potential for repair.
    Experimental Neurology 04/2006; 198(1):12-24. DOI:10.1016/j.expneurol.2005.11.006 · 4.70 Impact Factor
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