A restored functional cornea following transplantation of human ABCB5-positive limbal stem cells to limbal stem cell-deficient mice.
Limbal stem cells, which reside in the eye’s limbus, help maintain and regenerate corneal tissue. Their loss due to injury or disease is one of the leading causes of blindness.
In the past, tissue or cell transplants have been used to help the cornea regenerate, but it was unknown whether there were actual limbal stem cells in the grafts, or how many, and the outcomes were not consistent.
In this new study, researchers at the Massachusetts Eye and Ear/Schepens Eye Research Institute (Mass. Eye and Ear), Boston Children’s Hospital, Brigham and Women’s Hospital, and the VA Boston Healthcare System used a molecule known as ABCB5, which acts as a marker for hard-to-find limbal stem cells.
ABCB5 allowed the researchers to locate hard-to-find limbal stem cells in tissue from deceased human donors and use these stem cells to regrow anatomically correct, fully functional human corneas in mice.
“Limbal stem cells are very rare, and successful transplants are dependent on these rare cells,” says Bruce Ksander, Ph.D., of Mass. Eye and Ear, co-lead author on the study with post-doctoral fellow Paraskevi Kolovou, M.D. “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.”
ABCB5 was originally discovered in the lab of Markus Frank, M.D., of Boston Children’s Hospital, and Natasha Frank, M.D., of the VA Boston Healthcare System and Brigham and Women’s Hospital (co-senior investigators on the study) as being produced in tissue precursor cells in human skin and intestine.
In the new work, using a mouse model developed by the Frank lab, they found that ABCB5 also occurs in limbal stem cells and is required for their maintenance and survival, and for corneal development and repair. Mice lacking a functional ABCB5 gene lost their populations of limbal stem cells, and their corneas healed poorly after injury.
“ABCB5 allows limbal stem cells to survive, protecting them from apoptosis [programmed cell death],” says 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.” according to Natasha Frank.
Markus Frank is working with the biopharmaceutical industry to develop a clinical-grade ABCB5 antibody that would meet U.S. regulatory approvals.