Development of a Stem Cell-based Approach for Treating Corneal Endothelial Cell Deficiency

Funding Type: 
Early Translational IV
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Corneal endothelial cell deficiency is one of the leading causes of blindness in human beings. The goal of this proposal is to develop a strategy for transplanting stem-cell derived corneal endothelial cells (CECs) into the eyes of patients with CEC deficiency. In the past, transplantation of CECs from postmortem donors yielded encouraging initial therapeutic effects, but the lack of donor tissues prevents the procedure of corneal endothelial cell transplantation.

We therefore propose to convert human pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) into functional corneal endothelial cells (CECs). We will engineer CEC sheets that are suitable for transplantion in animal model. To establish that these cells are functional, we will assay molecular markers and measure physiological functions of CECs in the culture dish. Next, we will perform CEC transplantation in an animal model that mimic CEC deficiency in humans. Finally, we will test the safety of CEC cells by transplanting them into the relevant immune-deficient animal model to confirm no tumor formation. Our proposed project will pave the way for future use of stem cell-derived CECs in a clinical setting.

Statement of Benefit to California: 

Cornea dysfunction is the second-leading cause of blindness. Approximately 10-million patients worldwide are affected by some form of corneal disease, and many of them require corneal transplantation (or kerotoplasty). In the US, corneal transplantation is the most common organ transplantation (>15,000 cases/year). So far, donor corneal tissues are still the main source of corneal transplantation. However, due to the shortage of donors, only less than 1% patients receive surgery every year. Thus, procuring corneal grafts is a significant unmet medical need. Among the patients receiving cornea engraftment, 40% are related to failing corneal endothelial cells (CECs), which are essential for maintaining stroma hydration for cornea transparency.

Recent advancements in stem cell biology have opened new avenues to obtain CECs from pluripotent stem cell-derived neural crest cells. We therefore propose to establish in vitro differentiation protocols of CECs from human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). The function of stem cell-derived CECs can be evaluated in animal models of CEC deficiency via corneal endothelial cell transplantation procedure. Because hESCs and iPSCs can be expanded in a large quantity under cGMP condition, stem cell-derived CECs would be an unlimited source for CEC cell replacement therapy. Overall, our proposal studies will greatly benefit people in California in their vision care.