Transplanting human stem cells from umbilical cords onto the abnormally thin, cloudy corneas of laboratory mice significantly improved corneal transparency and increased the thickness of the animals’ corneal stroma, the transparent middle layer, according to a new study.
These research results come at a time of limited supply of donated human corneas for treating patients with severe corneal and genetic eye diseases.
Human umbilical cord mesenchymal stem cells (UMSCs) transplants may prove to be an alternative to corneal transplant surgeries.
The transplanted UMSCs survived in the mouse corneal stroma for more than three months with minimal signs of graft rejection, according to Winston Kao, Ph.D., of the University of Cincinnati School of Medicine.
In contrast, human umbilical hematopoietic stem cells (HUHSCs), the stem cells that give rise to all blood cells types, rapidly vanished from the mouse corneas when they were transplanted into the animals’ eyes.
Unlike the UMSCs, the HUHSCs were victims of graft-host rejection.
Kao said that histological and immune fluorescence staining showed that the transplanted UMSCs could trans-differentiate and assume the appearance of normal corneal keratocytes.
The new cells expressed critical keratocyte markers such as keratocan and aldehyde dehydrogenase as well as the adhesion protein, CD34, all with little or no graft reaction.
The animal model for these studies, a special knockout mouse, was genetically engineered to lack the gene for making lumican, a protein essential for the formation and maintenance of a transparent cornea. Knockout mice without lumican have thin and cloudy corneas.
The supply of human corneas for transplantation is under threat from an unexpected direction: laser eye surgery. Reconfiguring the refractive surface of the cornea through laser surgery unfortunately can leave the cornea unsuitable for later organ donation. About 50,000 corneal transplants are performed each year in the United States.
Kao believes that UMSC transplants as an alternative treatment for severe genetic and corneal diseases are well worth pursuing. Unlike donated corneas, the supply of human UMSCs is almost unlimited.
UMSCs are easy to isolate from the umbilical cord, their numbers can be expanded in cell culture, and they can be stored and quickly recovered from liquid nitrogen when a patient is in urgent need of a clear, healthy cornea.
“Corneal transplantation is currently the only true cure for restoration of eyesight that may have been lost due to corneal scarring caused by infection, mechanical and chemical wounds and congenital defects of genetic mutations,” Kao said. “However, the number of donated corneas suitable for transplantation is decreasing as the number of individuals receiving refractive surgeries, like LASIK, increases.”
Worldwide there is a shortage of suitable corneas for transplantation, and at the present time, there is no effective alternative procedure besides corneal transplantation to treat corneal blindness.
“There is a large need to develop alternative treatment regimens, one of which may be the transplantation of mesenchymal stem cells,” Kao said.
The research was presented at the American Society for Cell Biology (ASCB) annual meeting.
Contact: Winston W-Y Kao, 513-558-2802, Winston.Kao@UC.Edu
