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Researchers regrow corneas using adult human stem cells

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    a restored functional cornea following transplantation of human ABCB5-positive limbal stem cells to limbal stem cell-deficient mice. (Kira Lathrop, Bruce Ksander, Markus Frank, and Natasha Frank.)

Boston researchers have successfully regrown human corneal tissue – a feat that could potentially restore vision in the blind.

The achievement is groundbreaking as it marks one of the first times that scientists have constructed tissue using adult-derived human stem cells.

In a new study published in the journal Nature, researchers from Massachusetts Eye and Ear Institute, Boston Children’s Hospital, Brigham and Women’s Hospital and the VA Boston Healthcare System detailed their groundbreaking research.  According to the paper, the key to the study’s success revolves around a molecule known as ABCB5, which serves as a biomarker for previously elusive limbal stem cells.

Residing in the eye’s limbus – the border of the cornea and the whites of the eye – the limbal stem cells are responsible for maintaining and recreating corneal tissue.   Because of their regenerative ability, scientists have long hoped to harness these stem cells for regrowing human tissue in those with blindness due to corneal injury or disease.  

The only problem? They’ve been rather difficult to track down.

“[The corneal tissue] – this is a tissue that has inherent turnover capacity; the cells are being shed and being replaced continuously,” lead researcher Dr. Markus Frank, of Boston Children’s Hospital, told FoxNews.com. “This capacity to restore is produced by the limbal stem cell population, and while it’s known that such cells exist, the identity and their exact molecular markers…have not been known.”

Frank’s lab originally discovered the crucial ABCB5 molecule over 10 years ago, finding that it was present in skin and intestine precursor cells.  But more recently, his team revealed that ABCB5 was also an important component of the eye’s limbal stem cells, preventing them from undergoing apoptosis – or cell death.

To further prove ABCB5’s role in the eye, Frank and his team created two groups of mice – ones lacking a functional ABCB5 gene and ones with a fully functioning ABCB5 gene.  The mice lacking ABCB5 lost their population of limbal stem cells and were unable to repair injuries to their corneas.

“When we found this…we thought if we could enrich or isolate these ABCB5-positive cells and transplant them, they should be able to cure corneal disease,” Frank said.

Using the corneal tissue from deceased human donors, the researchers were able to locate the limbal stem cells using antibodies that bind to ABCB5.  Once they identified the stem cells, they extracted them from the donor tissue and transplanted them into mice whose limbal stem cells had been removed. As expected, fully normal human-derived corneal tissue was generated in the mice – allowing them to see once again.

Most importantly, the process only worked when the limbal stem cells contained the critical ABCB5 molecule.

“We showed that this capacity to regrow tissue was only located within the ABCB5-posivite graft,” Frank said. “When we grafted in the same setup the ABCB5-negative cells, these cells were unable to do that.”

Since the loss of corneal tissue is one of the leading causes of blindness, the researchers hope this process will serve as a way to reverse any damage to the cornea, using unadulterated stem cells. Past studies have attempted to help the cornea regenerate by doing tissue or cell transplants, but the outcomes have not been consistent.

“For the first step, we’re really working towards an autologous graft in patients who are blind in one eye,” Frank said. “And then the second step, we’d really work towards using donor derived cells to transplant in a similar manner that may require immune suppression – but it may not.”

Frank and his team hope to continue studying ABCB5, to see if it could serve a similar purpose for isolating skin stem cells for transplantation.  He noted that its identity as a molecular marker has changed the game when it comes to adult stem cell research.

“We’re glad to move this area forward, since [this marker] has really been the one thing missing in the field,” Franks said. “But if you have a specific molecular marker to sort these stem cells out and arrive at a pure cell product for transplantation, that’s huge.”

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