Scientists can now screen for stem cells that enhance corneal regrowth

July 2, 2014, Harvard University
This is a restored functional cornea following transplantation of human limbal stem cells to limbal stem cell-deficient mice. Credit: Kira Lathrop, Bruce Ksander, Markus Frank, and Natasha Frank.

A Boston-based scientific collaborative, led by Harvard Stem Cell Institute (HSCI) researchers, has discovered a way to collect the best cell type for regenerating a damaged cornea—the clear membrane that covers the pupil and directs light into the back of the eye. The investigators report in the journal Nature that purified human stem cells can be used to improve long-term vision in mice. The team is now pursuing FDA-approval for the technique before moving on to patient clinical trials.

The study, lead by co-senior investigators Natasha Frank, MD, and Markus Frank, MD, was a highly collaborative effort, with 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.

Corneal blindness is a clouding of vision that results when blood vessels grow into the cornea. It can be caused by an injury, infection, or autoimmune disease that destroys an actively regenerating population of located in an area behind the cornea, called the limbus. Limbal stem cell transplants from an uninjured or deceased organ donor have had promising results, but outcomes have been inconsistent.

"Previously published work on limbal epithelial cell grafts showed that when more than three percent of 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, who is a physician of the VA Boston Healthcare System and Brigham and Women's Hospital, and a Harvard Medical School assistant professor of medicine in the Division of Genetics at Brigham and Women's Hospital.

Composite image depicting the palisades of Vogt within the human limbus (left), ABCB5-positive limbal stem cells isolated from the palisades (right; ABCB5 -- green, nucleus -- red) and a restored functional cornea following transplantation of human ABCB5-positive limbal stem cells to limbal stem cell-deficient mice (bottom right). Credit: Kira Lathrop, Bruce Ksander, Markus Frank, and Natasha Frank.

The biological marker the researchers found is the ABCB5 protein, which is located on the surface of limbal stem cells. The team then developed an antibody that could tag limbal stem cells in a general sample of human limbal cells, making it possible to purify only the cells responsible for successful limbal cell transplants.

The researchers transplanted purified limbal stem cells from adult humans into mice with and checked to see if the corneas had regrown 5 weeks later, as well as 13 months later. They found that the mouse corneas looked normal, with 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 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.

This is an image depicting the palisades of Vogt within the human limbus. The human limbal architecture shows the palisades of Vogt in whole mounted tissue labeled with collagen VII and imaged with a laser scanning confocal microscope. Image is a stitched Z stack series. Credit: Kira Lathrop, Bruce Ksander, Markus Frank, and Natasha Frank.

The research team next hopes to find a way to replicate limbal stem cells so that a single donor eye can produce enough transplantable cells to help several patients. They will also be partnering with biopharmaceuticals 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 and co-first author on the study with postdoctoral fellow Paraskevi Kolovou, MD.

Explore further: Doctors perform living donor stem cell transplants in eye patients

More information: Ksander, et. al., ABCB5 is a limbal stem cell gene required for corneal development and repair. Nature. (July 2, 2014), DOI: 10.1038/nature13426

Related Stories

Doctors perform living donor stem cell transplants in eye patients

May 5, 2014
Debra Astrug, who once feared she was going blind, can see fine now, thanks to a stem cell transplant she received from her daughter, Jessica.

New cells found that could help save people's sight

November 8, 2012
Eye experts and scientists at the University of Southampton have discovered specific cells in the eye which could lead to a new procedure to treat and cure blinding eye conditions.

Research team pursues techniques to improve elusive stem cell therapy

June 30, 2014
Stem cell scientists had what first appeared to be an easy win for regenerative medicine when they discovered mesenchymal stem cells several decades ago. These cells, found in the bone marrow, can give rise to bone, fat, ...

Team finds switch that causes mature liver cells to revert back to stem cell-like state

June 5, 2014
Harvard Stem Cell Institute scientists at Boston Children's Hospital have new evidence in mice that it may be possible to repair a chronically diseased liver by forcing mature liver cells to revert back to a stem cell-like ...

Inner ear stem cells hold promise for restoring hearing

June 21, 2014
Spiral ganglion cells are essential for hearing and their irreversible degeneration in the inner ear is common in most types of hearing loss. Adult spiral ganglion cells are not able to regenerate. However, new evidence in ...

Recommended for you

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.