Looking to the Future of Stem Cell Eye Research

A Note from Majlinda Lako, Associate Editor of STEM CELLS

Sight is the most precious of all human senses and blindness is one of the most feared health threats. Worldwide, intensive research is being carried out to better understand the causes that lead to eye disease, to identify stem and progenitor cells with regenerative potential in various parts of the eye, and to conduct gene therapies for restoring vision. Many of the disorders that cause blindness are currently difficult to treat and Holoclar® is the only approved stem cell treatment for the eye. This treatment involves taking corneal stem cells from the patients, expanding these in the laboratory and transplanting them into the injured eye. This treatment is only applicable for patients that have some corneal stem cells left in their eyes for laboratory expansion.

Two ground-breaking clinical trials, led by Dr. Takahashi (Japan) and Astellas Institute of Regenerative Medicine, have transplanted retinal pigment epithelial cells (RPE) derived from human pluripotent stem cells into patients with Age-Related Macular Degeneration and Stargardt’s Macular Dystrophy. The long term outcomes of both trials are eagerly waited, however the initial results published by Astellas Institute of Regenerative Medicine phase I/II trial suggests that pluripotent stem cell-derived RPE do not cause any adverse effects upon transplantation, opening the path for promising phase III multi center trials.

STEM CELLS has had a long interest in stem cell therapies for eye disease. These noteworthy articles for this virtual issue encompass the breadth of research performed by stem cell scientists in the eye field, starting with lineage tracing of corneal epithelial stem cells, better understanding of their niche, and application of other epithelial stem cells for treatment of patients with bilateral corneal disease. A number of articles describe the application of cutting-edge genome editing technologies for purification of various eye cells and generation of disease models in a dish from pluripotent stem cells. Last but not least, these articles provide novel insights into how best to differentiate pluripotent stem cells into desired eye lineages and how to make these protocols robust and amenable to good manufacturing practice regulations.

This fast-paced stem and regenerative medicine field calls for more pioneering progress. We invite authors to submit their original research papers on transplantation of cells into various parts of the eye that may lead us closer to clinical application. Articles are subject to peer review and, if accepted, will appear in a new special Eye Series

On behalf of the Editors, I hope that you enjoy reading this excellent collection of recent manuscripts. We thank all of the authors for their commitment to their research and the Journal, and look forward to publishing new research on furthering this progress. 


A Re-interpretation of Cell Transplantation: GFP Transfer from Donor to Host Photoreceptors

Arturo Ortin-Martinez, En Leh Samuel Tsai, Philip E. Nickerson, Miriam Bergeret, Yao Lu, Sheila Smiley, Lacrimioara Comanita and Valerie A. Wallace
Accepted manuscript online: 14 DEC 2016, DOI: 10.1002/stem.2552


Generation of Storable Retinal Organoids and Retinal Pigmented Epithelium from Adherent Human iPS Cells in Xeno-Free and Feeder-Free Conditions

Sacha Reichman, Amélie Slembrouck, Giuliana Gagliardi, Antoine Chaffiol, Angélique Terray, Céline Nanteau, Anais Potey, Morgane Belle, Oriane Rabesandratana, Jens Duebel, Gael Orieux, Emeline F. Nandrot, José-Alain Sahel, Olivier Goureau
Version of record online: 20 FEB 2017, DOI: 10.1002/stem.2586


Regulation of WNT Signaling by VSX2 During Optic Vesicle Patterning in Human Induced Pluripotent Stem Cells

Elizabeth E. Capowski, Lynda S. Wright, Kun Liang, M. Joseph Phillips, Kyle Wallace, Anna Petelinsek, Anna Hagstrom, Isabel Pinilla, Katarzyna Borys, Jessica Lien, Jee Hong Min, Sunduz Keles, James A. Thomson and David M. Gamm
Version of Record online: 5 JUL 2016, DOI: 10.1002/stem.2414


Using Zinc Finger Nuclease Technology to Generate CRX-Reporter Human Embryonic Stem Cells as a Tool to Identify and Study the Emergence of Photoreceptors Precursors During Pluripotent Stem Cell Differentiation

Joseph Collin, Carla B Mellough, Birthe Dorgau, Stefan Przyborski, Inmaculada Moreno-Gimeno and Majlinda Lako
Version of Record online: 26 NOV 2015, DOI: 10.1002/stem.2240


Stepwise Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells Enables Analysis of Glaucomatous Neurodegeneration

Sarah K. Ohlemacher, Akshayalakshmi Sridhar, Yucheng Xiao, Alexandra E. Hochstetler, Mansoor Sarfarazi, Theodore R. Cummins and Jason S. Meyer
Version of Record online: 21 MAR 2016, DOI: 10.1002/stem.2356


Protective Effects of Human iPS-Derived Retinal Pigmented Epithelial Cells in Comparison with Human Mesenchymal Stromal Cells and Human Neural Stem Cells on the Degenerating Retina in rd1 mice

Jianan Sun, Michiko Mandai, Hiroyuki Kamao, Tomoyo Hashiguchi, Masayuki Shikamura, Shin Kawamata, Sunao Sugita and Masayo Takahashi
Version of Record online: 23 APR 2015, DOI: 10.1002/stem.1960


Transplantation of Photoreceptor Precursors Isolated via a Cell Surface Biomarker Panel From Embryonic Stem Cell-Derived Self-Forming Retina

Jorn Lakowski, Anai Gonzalez-Cordero, Emma L. West, Ya-Ting Han, Emily Welby, Arifa Naeem, Samuel J. I. Blackford, James W. B. Bainbridge, Rachael A. Pearson, Robin R. Ali and Jane C. Sowden
Version of Record online: 27 MAY 2015, DOI: 10.1002/stem.2051


Transcriptome Dynamics of Developing Photoreceptors in Three-Dimensional Retina Cultures Recapitulates Temporal Sequence of Human Cone and Rod Differentiation Revealing Cell Surface Markers and Gene Networks

Rossukon Kaewkhaw, Koray Dogan Kaya, Matthew Brooks, Kohei Homma, Jizhong Zou, Vijender Chaitankar, Mahendra Rao and Anand Swaroop
Version of Record online: 14 AUG 2015, DOI: 10.1002/stem.2122


Cell Adhesion Molecules and Stem Cell-Niche-Interactions in the Limbal Stem Cell Niche

Naresh Polisetti, Matthias Zenkel, Johannes Menzel-Severing, Friedrich E. Kruse and Ursula Schlötzer-Schrehardt
Version of Record online: 11 SEP 2015, DOI: 10.1002/stem.2191


Tracing the Fate of Limbal Epithelial Progenitor Cells in the Murine Cornea

N. Di Girolamo, S. Bobba, V. Raviraj, N. C. Delic, I. Slapetova, P. R. Nicovich, G. M. Halliday, D. Wakefield, R. Whan and J. G. Lyons
Version of Record online: 18 DEC 2014, DOI: 10.1002/stem.1769


Lineage Tracing of Stem and Progenitor Cells of the Murine Corneal Epithelium

Aya Amitai-Lange, Anna Altshuler, Jeffrey Bubley, Noora Dbayat, Beatrice Tiosano and Ruby Shalom-Feuerstein
Version of Record online: 18 DEC 2014, DOI: 10.1002/stem.1840


Concise Review: Transplantation of Cultured Oral Mucosal Epithelial Cells for Treating Limbal Stem Cell Deficiency—Current Status and Future Perspectives

Tor Paaske Utheim
Version of Record online: 21 MAY 2015, DOI: 10.1002/stem.1999

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Video Highlights

Video abstract from Drs. Banerjee, Surendran, Bharti, Morishita, Varshney, and Pal on their recently published STEM CELLS paper entitled, "Long non-coding RNA RP11-380D23.2 drives distal-proximal patterning of the lung by regulating PITX2 expression." Read the paper here.

Video abstract from Drs. Sayed, Ospino, Himmati, Lee, Chanda, Mocarski, and Cooke on their recently published STEM CELLS paper entitled, "Retinoic Acid Inducible Gene 1 Protein (RIG1)-like Receptor Pathway is Required for Efficient Nuclear Reprogramming." Read the paper here.

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