Corneal abrasions are some of the most common eye injuries. While many heal up just fine, others can result in blindness and over 40,000 corneal transplants are done every year in the United States, with variable outcomes. Identifying the stem cells that regenerate corneas comes from a recent study involving a wide collaboration between healthcare facilities in Boston. Targeting the stem cells not only resulted in an increased success in corneal transplants, but is one of the first known instances of using adult-derived stem cells to regenerate tissue. The results of the research were published in Nature.
Guaranteeing a successful corneal transplant has traditionally been quite difficult, as limbal stem cells (the cells that create and maintain the cornea) are limited in number. Their presence can make or break the success a corneal transplant, but it has not always been easy to identify them for transplantation. This study’s success hinged on using the protein ABCB5 to identify the limbal stem cells. The human corneas were then implanted into mice, where they developed and became fully functional once again.
"Limbal stem cells are very rare, and successful transplants are dependent on these rare cells," lead author Bruce Ksander said in a press release. "This finding will now make it much easier to restore the corneal surface. It's a very good example of basic research moving quickly to a translational application.”
The co-senior investigators in the study were Markus and Natasha Frank, who previously discovered ABCB5 in cells that are precursors for human skin and intestine. It was discovered during this recent study that ABCB5 is also found in limbal stem cells and the health and integrity of the cornea depends on it. By knocking out the gene that produces the protein, they found that mice would lack in limbal stem cells, and trauma to the cornea did not heal nearly as well compared to mice with a functional gene.
"ABCB5 allows limbal stem cells to survive, protecting them from apoptosis [programmed cell death]," added Markus Frank. "The mouse model allowed us for the first time to understand the role of ABCB5 in normal development, and should be very important to the stem cell field in general.”
Currently, Markus Frank is working on developing an antibody for ABCB5 that can be used in human clinical trials, and he is getting help from others in the pharmaceutical industry. The entire study has been a testament to the benefits of collaborating with others—a fact that has not been overlooked by Natasha Frank.
"A single lab cannot do a study like this," she stated. "It integrates genetics, knockout mice, antibodies, transplantation—a lot of technical expertise that we were lucky came together in a very nice way."
