More than 3.2 million people worldwide are blind in both eyes due to corneal diseases. Limbal stem cell deficiency (LSCD) has been recognized as a major cause, either primary or secondary, of significant visual loss and blindness in many common corneal disorders. The corneal epithelium is constantly renewed and maintained by the limbal stem cells (LSCs) that are presumed to reside at the limbus, the junction between the cornea and conjunctiva. When LSCs are deficient and unable to repopulate the corneal surface, the cornea will become opaque. A corneal transplant is unable to survive and is contraindicated in LSCD. In patients who have LSCD in only one eye, LSCs can be obtained by a small biopsy from the healthy eye and expanded in culture. Transplantation of these expanded LSCs can restore sight in the affected eye. In patients who have LSCD in both eyes, LSCs will need to be regenerated from another cell source. The goal of the proposed research is to regenerate autologous LSCs from skin epithelial stem cells for transplantation. We plan to use a new method that provides the LSC niche factors necessary to maintain the corneal epithelial fate to facilitate the transdifferentiation of SESCs into LSCs. The efficiency of the transdifferentiation will be further optimized by modulating regulatory pathways. The success of this research not only will develop a much needed cell therapy to restore sight but also will establish a new model for stem cell therapy in other diseases.
Statement of Benefit to California:
This proposal is to develop a stem cell transplantation therapy for treating a blinding corneal disorder, bilateral limbal stem cell deficiency (LSCD). Because of visual impairment, patients with LSCD lose the ability to drive, read, and watch TV. In addition, they experience recurrent corneal erosion that causes severe pain. Recurrent breakdown of the corneal surface increases the risk of infection that requires frequent medical intervention. All of these factors can have a substantially negative psychological impact on patients and their families. Therefore, LSCD imposes a significant social and economic impact on society.
California is the most populated state in the US. More than 36 million people reside in the State of California, and the population is expected to increase to 46 million by 2030. Accordingly, the number of residents with LSCD is likely to increase disproportionately as a result of occupational and environmental risk factors. A new treatment to restore vision would be an important benefit to the people of California.
Further, the project would train new stem cell researchers and provide innovation in stem cell therapy. When this project enters the clinical phase, it will bring together new physicians and scientists and attract funding by the federal government and investment from biotechnology companies in California. Stem cell–based transplantation to treat a stem cell–related disease such as LSCD is well aligned with the broad mission of CIRM.