Directing human induced pluripotent stem cells into a neurosensory lineage for auditory neuron replacement.
AuthorGunewardene, N; Bergen, NV; Crombie, D; Needham, K; Dottori, M; Nayagam, BA
Source TitleBioResearch Open Access
PublisherMary Ann Liebert Inc
University of Melbourne Author/sDottori, Mirella; Nayagam, Bryony; Needham, Karina; Gunewardene, Niliksha; van Bergen, Nicole; Crombie, Duncan
Audiology and Speech Pathology
Florey Department of Neuroscience and Mental Health
Document TypeJournal Article
CitationsGunewardene, N., Bergen, N. V., Crombie, D., Needham, K., Dottori, M. & Nayagam, B. A. (2014). Directing human induced pluripotent stem cells into a neurosensory lineage for auditory neuron replacement.. Biores Open Access, 3 (4), pp.162-175. https://doi.org/10.1089/biores.2014.0019.
Access StatusAccess this item via the Open Access location
Open Access URLhttps://europepmc.org/articles/PMC4120935?pdf=render
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120935
Emerging therapies for sensorineural hearing loss include replacing damaged auditory neurons (ANs) using stem cells. Ultimately, it is important that these replacement cells can be patient-matched to avoid immunorejection. As human induced pluripotent stem cells (hiPSCs) can be obtained directly from the patient, they offer an opportunity to generate patient-matched neurons for transplantation. Here, we used an established neural induction protocol to differentiate two hiPSC lines (iPS1 and iPS2) and one human embryonic stem cell line (hESC; H9) toward a neurosensory lineage in vitro. Immunocytochemistry and qRT-PCR were used to analyze the expression of key markers involved in AN development at defined time points of differentiation. The hiPSC- and hESC-derived neurosensory progenitors expressed the dorsal hindbrain marker (PAX7), otic placodal marker (PAX2), proneurosensory marker (SOX2), ganglion neuronal markers (NEUROD1, BRN3A, ISLET1, ßIII-tubulin, Neurofilament kDa 160), and sensory AN markers (GATA3 and VGLUT1) over the time course examined. The hiPSC- and hESC-derived neurosensory progenitors had the highest expression levels of the sensory neural markers at 35 days in vitro. Furthermore, the neurons generated from this assay were found to be electrically active. While all cell lines analyzed produced functional neurosensory-like progenitors, variabilities in the levels of marker expression were observed between hiPSC lines and within samples of the same cell line, when compared with the hESC controls. Overall, these findings indicate that this neural assay was capable of differentiating hiPSCs toward a neurosensory lineage but emphasize the need for improving the consistency in the differentiation of hiPSCs into the required lineages.
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References
- Minerva Elements Records 
- Florey Department of Neuroscience and Mental Health - Research Publications 
- Paediatrics (RCH) - Research Publications 
- Medical Bionics - Research Publications 
- Otolaryngology - Research Publications 
- Audiology and Speech Pathology - Research Publications 
- Biomedical Engineering - Research Publications