Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles

Akihiro J. Matsuoka, Zafar A. Sayed, Nicholas Stephanopoulos, Eric J. Berns, Anil R. Wadhwani, Zachery D. Morrissey, Duncan M. Chadly, Shun Kobayashi, Alexandra N. Edelbrock, Tomoji Mashimo, Charles A. Miller, Tammy L. McGuire, Samuel I Stupp, John A. Kessler

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Article numbere0190150
JournalPLoS One
Volume12
Issue number12
Publication statusPublished - Dec 1 2017

Fingerprint

isoleucyl-lysyl-valyl-alanyl-valine
Stem Cell Niche
Amphiphiles
Inner Ear
Stem cells
stem cells
ears
niches
peptides
Peptides
Gels
gels
embryonic stem cells
Spiral Ganglion
Cell Survival
Injections
neurites
Neurites
injection
cell viability

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Matsuoka, A. J., Sayed, Z. A., Stephanopoulos, N., Berns, E. J., Wadhwani, A. R., Morrissey, Z. D., ... Kessler, J. A. (2017). Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles. PLoS One, 12(12), [e0190150].

Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles. / Matsuoka, Akihiro J.; Sayed, Zafar A.; Stephanopoulos, Nicholas; Berns, Eric J.; Wadhwani, Anil R.; Morrissey, Zachery D.; Chadly, Duncan M.; Kobayashi, Shun; Edelbrock, Alexandra N.; Mashimo, Tomoji; Miller, Charles A.; McGuire, Tammy L.; Stupp, Samuel I; Kessler, John A.

In: PLoS One, Vol. 12, No. 12, e0190150, 01.12.2017.

Research output: Contribution to journalArticle

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 2017, 'Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles', PLoS One, vol. 12, no. 12, e0190150.
Matsuoka AJ, Sayed ZA, Stephanopoulos N, Berns EJ, Wadhwani AR, Morrissey ZD et al. Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles. PLoS One. 2017 Dec 1;12(12). e0190150.
Matsuoka, Akihiro J. ; Sayed, Zafar A. ; Stephanopoulos, Nicholas ; Berns, Eric J. ; Wadhwani, Anil R. ; Morrissey, Zachery D. ; Chadly, Duncan M. ; Kobayashi, Shun ; Edelbrock, Alexandra N. ; Mashimo, Tomoji ; Miller, Charles A. ; McGuire, Tammy L. ; Stupp, Samuel I ; Kessler, John A. / Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles. In: PLoS One. 2017 ; Vol. 12, No. 12.
@article{a97405ebbec14a4fa8dcbfea9d168430,
title = "Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles",
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.",
author = "Matsuoka, {Akihiro J.} and Sayed, {Zafar A.} and Nicholas Stephanopoulos and Berns, {Eric J.} and Wadhwani, {Anil R.} and Morrissey, {Zachery D.} and Chadly, {Duncan M.} and Shun Kobayashi and Edelbrock, {Alexandra N.} and Tomoji Mashimo and Miller, {Charles A.} and McGuire, {Tammy L.} and Stupp, {Samuel I} and Kessler, {John A.}",
year = "2017",
month = "12",
day = "1",
language = "English",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles

AU - Matsuoka, Akihiro J.

AU - Sayed, Zafar A.

AU - Stephanopoulos, Nicholas

AU - Berns, Eric J.

AU - Wadhwani, Anil R.

AU - Morrissey, Zachery D.

AU - Chadly, Duncan M.

AU - Kobayashi, Shun

AU - Edelbrock, Alexandra N.

AU - Mashimo, Tomoji

AU - Miller, Charles A.

AU - McGuire, Tammy L.

AU - Stupp, Samuel I

AU - Kessler, John A.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85039791174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039791174&partnerID=8YFLogxK

M3 - Article

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e0190150

ER -