28 December 2015. A biotechnology company designed a process for generating human cornea cells from embryonic stem cells, without a donated cornea, the current replacement therapy. The team from Ocata Therapeutics Inc. led by Robert Lanza, the company’s chief scientist, published its proof-of-concept findings last week in the journal PLoS One.
Lanza and colleagues — from University of Miami, Stanford University, and University of California in San Diego — are seeking a reliable method for regenerating corneal endothelial cells in the lab, which can be transplanted in patients whose corneas are diseased or damaged. The cornea is the outer lens in the front of the eye that helps focus the eyes. The cells that line the inside of the cornea, known as corneal endothelial cells, pump fluid out of the cornea. Corneal endothelial cells, if damaged, cannot repair themselves,and must be replaced.
Transplants of the cornea are a relatively common procedure and often conducted with a local anesthetic, but like most organ transplants, the number of potential recipients far exceeds the number of donors. Corneas for transplant are currently provided by recently deceased donors who will their corneas to an eye bank that tests the cornea for safety and makes them available to transplant surgeons. Donated corneas can be transplanted up to 14 days following their recovery. A newer procedure, called lamellar keratoplasty, replaces only the corneal endothelial cells rather than the entire cornea, but still requires tissue from a deceased donor.
Ocata, in Marlborough, Massachusetts, develops regenerative therapies from stem cells, concentrated largely on stem cell treatments for eye diseases including Stargardt’s disease, dry age-related macular degeneration, myopic macular degeneration, and retinitis pigmentosa. The company’s treatments for Stargardt’s disease, dry age-related macular degeneration, and myopic macular degeneration are currently in clinical trials. Ocata says its technology platform based on human embryonic stem cells produces unlimited, replenishable quantities of these therapeutic cells.
In the study, researchers used Ocata’s technology to generate stem cells that transform into corneal endothelial cells, first in a stem cell medium, then in a medium encouraging corneal cell growth, a process taking 17 days. The team compared the form and structure of the generated cells to corneal endothelial cells from recently deceased individuals, as well as their expression of characteristic biomarkers and genes.
Results show the stem cell-derived corneal endothelial cells, called hESC-CECs, were nearly identical in form and structure to cells from the human samples. The generated cells also produced characteristic Zona Occludens 1 and ATPA1 proteins from those cells, as well as collagen-related proteins from the adjacent Descemet’s membrane. In addition, the genes expressed by stem cell-derived corneal endothelial cells were 96 percent identical to those from human samples.
“We have developed a simple, two-step method for generating amounts of hESC-CECs, in-vitro, which does not rely on donor corneas,” says Lanza in a company statement. “The ability to manufacture these cells from a single, replenishable stem cell source may provide a potential solution to the worldwide shortage of transplantable corneal tissue.”
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