Review: corneal endothelial cell derivation methods from ES/iPS cells.
Shin Hatou1, Shigeto Shimmura1
1Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomchi, Shinjuku-ku, Tokyo, Japan.
Inflammation and Regeneration
|October 9, 2019
Summary
Regenerative therapy using stem cells offers a promising solution for corneal blindness, addressing the significant gap in corneal transplantation needs. Research is advancing methods to derive corneal endothelial cells from stem cells for future therapies.
Area of Science:
- Ophthalmology and Regenerative Medicine
- Stem Cell Biology and Tissue Engineering
Background:
- A critical global shortage exists for corneal transplantation, with 12.7 million patients awaiting procedures against only 185,000 annual transplants.
- Corneal endothelial dysfunction, including bullous keratopathy from Fuchs' dystrophy or surgical complications, accounts for half of all corneal transplant indications.
- Developing regenerative therapies for corneal endothelium independent of donor corneas is crucial to bridge the supply-demand gap and combat corneal blindness.
Purpose of the Study:
- To review and analyze methods for deriving corneal endothelial cells (CECs) from pluripotent stem cells (ESCs/iPSCs).
- To explore the developmental mechanisms underlying CEC differentiation, including key signaling pathways.
- To assess the progress and challenges in translating these stem cell-derived CECs towards clinical applications for bullous keratopathy.
Main Methods:
- Review of four representative methods for deriving CECs from embryonic stem (ES) or induced pluripotent stem (iPS) cells.
- Analysis of evolving culture media components, transitioning from undefined sources (e.g., fetal bovine serum) to chemically defined media with recombinant proteins and small molecules.
- Examination of research elucidating the roles of TGF-beta, BMP, and Wnt signaling in epithelial-mesenchymal and mesenchymal-endothelial transitions during CEC development.
Main Results:
- Significant advancements have been made in refining CEC derivation protocols, moving towards chemically defined and more efficient methods.
- Key developmental pathways (TGF-beta, BMP, Wnt) have been identified as critical regulators of CEC differentiation from stem cells.
- Current protocols show promise for clinical translation, though further optimization is needed.
Conclusions:
- Stem cells (ESCs/iPSCs) represent an ideal cell source for regenerative therapy to treat corneal endothelial dysfunction, potentially solving the transplant shortage.
- Progress in understanding CEC developmental biology has enabled the development of improved, chemically defined derivation protocols.
- Future research must focus on rigorous proof of efficacy and safety in adequate animal models to facilitate clinical application of stem cell-derived CECs.
