Ocular stem cell regeneration

Cell Therapy, Completed Projects, Gene Editing, Quality of Life Change
About This Project

Stem cell regeneration of the ocular surface in Recessive Dystrophic Epidermolysis Bullosa

Lay summary

The cornea, the transparent outer surface of the eye which covers the iris and pupil, is important in bending light that enters the eye into a precise point, enabling clear vision. The cornea is fragile and frequently damaged in Recessive Dystrophic Epidermolysis Bullosa (RDEB) by trauma as minor as opening the eyes after sleep. This can lead to irreversible damage, excruciating pain and blindness.

This project – an extension of the previously funded limbal stem cells project – developed a 3D cornea with limbal stem cells (corneal stem cells) with functioning Collagen VII. It combines cutting-edge gene and stem cell technologies to create a local treatment creating a protective barrier to prevent corneal abrasion in an animal model.

Scientific Summary

Hematopoietic cell transplant cannot reach all parts of the body. The cornea, the main structure for refraction of light entering the eye, is a prime example. The cornea is frequently damaged in RDEB, and those affected are left with one of the most overwhelmingly irreversible ravages of this disease in terms of both pain and blindness.

In the previously funded limbal stem cells project , human skin and eye cells were reprogrammed into induced pluripotent stem (iPS) cells – cells that have been gene edited to restore type VII collagen gene function – and then differentiated them into corneal epithelial cells (limbal stem cells). To extend this proof‐of‐concept strategy to establish a high‐quality preclinical platform for a novel local therapy of corneal disease in people with RDEB, this project:

  • Developed cell sheets and 3D cornea using nano‐fiber scaffolds with limbal stem cells and corneal epithelial cells derived from iPS cells.
  • Defined culture conditions for differentiation of iPS cells into a subpopulation of limbal cells expressing ATP binding cassette subfamily B member 5 (ABCB5) with unique capacity to regenerate diseased corneal tissue.
  • Demonstrated functionality of epidermal sheets and 3D corneal grafts populated with iPS cell‐derived ABCB5 in which RDEB causing mutations in type VII collagen gene are gene edited using the CRISPR/Cas9 system.