July 3, 2014
Human Stem Cells Lead To Corneal Regrowth, Improved Vision In Mice
Rebekah Eliason for redOrbit.com – Your Universe Online
In an exciting new study, researchers have discovered a way to collect cells for the regeneration of corneal tissue – the clear membrane covering the pupil that directs light into the back of the eye.
The research team from Boston reported that purified human stem cells were used to improve long-term vision in mice. Currently, the team is waiting for FDA-approval to begin patient clinical trials.
This collaborative research effort was led by Natasha Frank, MD, and Markus Frank, MD, using work done at Massachusetts Eye and Ear/Schepens Eye Research Institute, Boston Children's Hospital, Brigham and Women's Hospital, and the US Department of Veterans Affairs Boston Healthcare System.
In some people blood vessels grow onto the cornea, vision clouding known as corneal blindness results. This condition is caused when limbus stem cells, located behind the cornea, are destroyed by injury, infection or autoimmune disease. Outcomes are inconsistent, but limbal stem cell transplants from an uninjured eye or deceased organ donor have had promising results.
"Previously published work on limbal epithelial cell grafts showed that when more than three percent of transplanted cells were stem cells, transplants were successful—less than three percent and the transplants were not," said HSCI Affiliated Faculty member Natasha Frank.
"The question in the field then was whether we could enrich the limbal stem cells. But until this study there was no specific marker that could isolate these cells," added Frank.
In this study, researchers have discovered the biological marker ABCB5 protein that is located on the surface of the limbal stem cells. In order to purify only the cells responsible for successful limbal cell transplants, the team developed an antibody that could mark limbal cells in a sample of general human limbal cells.
"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.
Researchers successfully transplanted purified limbal stem cells from adult humans into mice with corneal blindness. At five weeks and thirteen months, the team checked to see if the corneas had re-grown. They discovered that the mice corneas were normal and even had the same thickness and protein expression as corneas in healthy mice.
"I think a very exciting part of the study is that even though there is a lot of evidence that adult stem cells contribute to tissue regeneration, what we see is basically the first evidence that you can take adult stem cells and regrow the organ that's been damaged," Frank said.
In future research, the team plans to search for a way to replicate limbal stem cells. This would allow a single donor eye to produce enough transplantable cells to help several different patients. In addition they will partner with biopharmaceutical companies to produce commercial qualities of the ABCB5 antibody for humans, and they are planning to further collaborate with co-author Victor Perez, MD, a professor of ophthalmology at the Bascom Palmer Eye Institute in Miami, to move the techniques used in the current study into clinical trials.
"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 translational application," said Bruce Ksander, PhD, an associate scientist at Schepens Eye Research Institute.
This study was published in the journal Nature.