RRC ID 53173
Author Matsuoka AJ, Sayed ZA, Stephanopoulos N, Berns EJ, Wadhwani AR, Morrissey ZD, Chadly DM, Kobayashi S, Edelbrock AN, Mashimo T, Miller CA, McGuire TL, Stupp SI, Kessler JA.
Title Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles.
Journal PLoS ONE
Abstract The use of human embryonic stem cells (hESCs) for regeneration of the spiral ganglion will require techniques for promoting otic neuronal progenitor (ONP) differentiation, anchoring of cells to anatomically appropriate and specific niches, and long-term cell survival after transplantation. In this study, we used self-assembling peptide amphiphile (PA) molecules that display an IKVAV epitope (IKVAV-PA) to create a niche for hESC-derived ONPs that supported neuronal differentiation and survival both in vitro and in vivo after transplantation into rodent inner ears. A feature of the IKVAV-PA gel is its ability to form organized nanofibers that promote directed neurite growth. Culture of hESC-derived ONPs in IKVAV-PA gels did not alter cell proliferation or viability. However, the presence of IKVAV-PA gels increased the number of cells expressing the neuronal marker beta-III tubulin and improved neurite extension. The self-assembly properties of the IKVAV-PA gel allowed it to be injected as a liquid into the inner ear to create a biophysical niche for transplanted cells after gelation in vivo. Injection of ONPs combined with IKVAV-PA into the modiolus of X-SCID rats increased survival and localization of the cells around the injection site compared to controls. Human cadaveric temporal bone studies demonstrated the technical feasibility of a transmastoid surgical approach for clinical intracochlear injection of the IKVAV-PA/ONP combination. Combining stem cell transplantation with injection of self-assembling PA gels to create a supportive niche may improve clinical approaches to spiral ganglion regeneration.
Volume 12(12)
Pages e0190150
Published 2017-12-28
DOI 10.1371/journal.pone.0190150
PII PONE-D-17-31451
PMID 29284013
PMC PMC5746215
MeSH Animals Cell Differentiation Cell Transplantation Cells, Cultured Ear, Inner / cytology Ear, Inner / metabolism* Humans Peptides / metabolism* Rats Stem Cell Niche*
IF 2.766
Rats F344-Il2rgem7Kyo (strainID=1099)