BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

Abstract

Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM). Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel), in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC) integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF) treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN).

Crafting Polymeric and Peptidic Hydrogels for Improved Wound Healing

“…Another application of self‐assembling peptide‐based hydrogels is in neural regeneration. In humans, deterioration of the auditory nerve (AN) in the inner ear caused by diseases or lesions from surgery, trauma, tumors, or auditory neuropathy is irreversible and eventually leads to complete hearing loss in patients . Hearing impairments of this nature cannot be fixed by hearing aids or cochlear implants as these clinical solutions are designed for patients with cochlear sensorineural hearing loss.…”

“…Hearing impairments of this nature cannot be fixed by hearing aids or cochlear implants as these clinical solutions are designed for patients with cochlear sensorineural hearing loss. The success of cochlear implants depends on the proper transduction of electrical signals of the AN, and for patients with damaged ANs, such clinical treatments are futile . One possible treatment developed for healing loss due to AN damage is auditory brainstem implants (ABIs).…”

Tailor-Made Electrospun Culture Scaffolds Control Human Neural Progenitor Cell Behavior—Studies on Cellular Migration and Phenotypic Differentiation

“…We previously reported efficient use of mitogen-expanded human neural progenitor cell (HNPC) lines in neurorestorative studies, in in vitro and in vivo models of the CNS [25]- [30]. These cells respond to physical cues, with increased cell survival and graft-host integration in vivo by using a nanofiber gel as supporting scaffold [31] [32]. Also, chemical cues affect behavior of such cells, as we presented in studies using a co-culture with explanted brain tissue [29], a specific cocktail for dopaminergic neuron differentiation [25], or by different culture media [30].…”

Electrophysiological Profile of Differentiating Human Central Canal Ependymal Stem-Progenitor Cells

“…Compared to FBS alone, addition of BDNF to culture promotes a significant increase in neuronal differentiation (as measured by βIII-tubulin expression) and neurite outgrowth, an effect which diminishes with time in culture as a result of a critical period in differentiation being reached, wherein BDNF is no longer required for further differentiation and survival 108 . Neural precursors derived from human embryonic tissue injected into the auditory nerve of mice show significantly more proliferation, substantially greater numbers of differentiated neurons, and significantly more fiber outgrowth when BDNF is included in the injection 109 . Cultured hESCs from umbilical cord blood show significantly more GABAergic neural differentiation 99 through MAPK/ERK signaling an upregulation of p35 (a neuron-specific gene that activates cyclin-dependent kinase 5, required for proper CNS development 110 ) and greater survival of neuron-like cells when BDNF was present, with PI3K/Akt and MAPK/ERKdependent upregulation of the anti-apoptotic B cell lymphoma 2 gene 97 .…”

“…,100,109 . Input resistance is not significantly different between or within conditions regardless of TIC.…”