cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness

Luke A Wiley; Erin R Burnight; Adam P DeLuca; Kristin R Anfinson; Cathryn M Cranston; Emily E Kaalberg; Jessica A Penticoff; Louisa M Affatigato; Robert F Mullins; Edwin M Stone; Budd A Tucker

doi:10.1038/srep30742

Back

cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness

Journal article

Open access

Peer reviewed

cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness

Luke A Wiley, Erin R Burnight, Adam P DeLuca, Kristin R Anfinson, Cathryn M Cranston, Emily E Kaalberg, Jessica A Penticoff, Louisa M Affatigato, Robert F Mullins, Edwin M Stone, …

Scientific reports, Vol.6(1), pp.30742-30742

07/29/2016

DOI: 10.1038/srep30742

PMCID: PMC4965859

PMID: 27471043

Files and links (1)

url

https://doi.org/10.1038/srep30742View

Published (Version of record) Open Access

Abstract

Immunologically-matched, induced pluripotent stem cell (iPSC)-derived photoreceptor precursor cells have the potential to restore vision to patients with retinal degenerative diseases like retinitis pigmentosa. The purpose of this study was to develop clinically-compatible methods for manufacturing photoreceptor precursor cells from adult skin in a non-profit cGMP environment. Biopsies were obtained from 35 adult patients with inherited retinal degeneration and fibroblast lines were established under ISO class 5 cGMP conditions. Patient-specific iPSCs were then generated, clonally expanded and validated. Post-mitotic photoreceptor precursor cells were generated using a stepwise cGMP-compliant 3D differentiation protocol. The recapitulation of the enhanced S-cone phenotype in retinal organoids generated from a patient with NR2E3 mutations demonstrated the fidelity of these protocols. Transplantation into immune compromised animals revealed no evidence of abnormal proliferation or tumor formation. These studies will enable clinical trials to test the safety and efficiency of patient-specific photoreceptor cell replacement in humans.

Details

Title: Subtitle: cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness
Creators: Luke A Wiley - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Erin R Burnight - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Adam P DeLuca - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Kristin R Anfinson - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Cathryn M Cranston - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Emily E Kaalberg - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Jessica A Penticoff - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Louisa M Affatigato - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Robert F Mullins - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Edwin M Stone - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Budd A Tucker - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Scientific reports, Vol.6(1), pp.30742-30742
DOI: 10.1038/srep30742
PMID: 27471043
PMCID: PMC4965859
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: DP2 OD007483 / NIH HHS R01 EY024588 / NEI NIH HHS R01 EY024605 / NEI NIH HHS
Language: English
Date published: 07/29/2016
Academic Unit: The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Center for Bioinformatics and Computational Biology; Ophthalmology and Visual Sciences
Record Identifier: 9983980078602771

Metrics

21 Record Views

92 Times Cited - Web of Science