Scientists regrow human corneas from adult stem cells

In a breakthrough, scientists have successfully regrown human corneas from an extremely rare kind of adult stem cell harvested from deceased donors.
Researchers identified a way to enhance regrowth of human corneal tissue to restore vision, using a molecule known as ABCB5 that acts as a marker for hard-to-find limbal stem cells.
Limbal stem cells - identified with a new marker - could reverse a leading cause of blindness, researchers said.
The research at the Massachusetts Eye and Ear Research Institute provides promise to burn victims, victims of chemical injury and others with damaging eye diseases.
It is also one of the first known examples of constructing a tissue from an adult-derived human stem cell.

Limbal stem cells reside in the eye's basal limbal epithelium, or limbus, and 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 the study, researchers were able to use antibodies detecting ABCB5 to zero in on the stem cells in tissue from deceased human donors and use them 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," said Bruce Ksander, co-lead author on the study with post-doctoral fellow Paraskevi Kolovou.
"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," said Ksander.
ABCB5 was originally discovered in the lab of Markus Frank, of Boston Children's Hospital, and Natasha Frank, 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]," said 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," said Natasha.

The research was published in the journal Nature.