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Corneal epithelial stem cell transplant results encouraging
A bioengineered corneal surface could help many patients. Ethical issues may be addressed as knowledge about stem cells grows.
SACRAMENTO, Calif. — Bioengineered corneal surfaces being developed here and elsewhere might benefit between 2,000 and 4,000 patients per year, according to Ivan Schwab, MD, a professor of ophthalmology here at the University of California-Davis (UC-Davis).
Conventional corneal transplants can fail in patients with an insufficient supply of immature corneal cells to generate a new corneal epithelium. Dr. Schwab's group here and a number of others around the world are working on the development of a bioengineered corneal surface.
Dr. Schwab and colleagues at UC-Davis have used a bioengineered composite of human amniotic membrane and adult corneal epithelial stem cells to treat patients with compromised corneal surfaces. Patients who are candidates for the bioengineered corneal surface include those with alkali burns or certain inflammatory diseases that have caused underlying damage to the corneal surface replicative cells, Dr. Schwab said in an interview with Ocular Surgery News.
In the procedure, limbal stem cells are harvested either from the patient or a relative and planted on a piece of amniotic tissue. Within 2 to 3 weeks these cells grow and mature at room temperature, forming a matrix of corneal surface cells.
Dr. Schwab's team cultured a large number of immature corneal precursor cells and froze some for possible later use. They transplanted these lab-grown cell matrices into a total of 14 patients. In 10 cases the matrices were grown from cells harvested from the patient's own eyes; in 4 cases the cells came from the eyes of related donors.
Of the total of 14 transplants, 10 were successful, Dr. Schwab said. Success was defined as restoration of the corneal surface as well as either stabilized or improved vision.
According to R. Rivkah Isseroff, a UC-Davis cell biologist, the only types of bioengineered replacement tissue commercially available are skin to treat burns and wounds and cartilage to treat some knee injuries. She hopes that the corneal surface tissue being developed at Davis become a third type of bioengineered tissue available.
Taiwanese studies
Ray Jui-Fang Tsai, MD, a professor of ophthalmology at Chang Chung Memorial Hospital in Taiwan, directed studies that included six patients who received tissues generated from their own corneas; the patients had a mean visual acuity improvement from 20/112 preop to 20/45 postop, he said. Another study of 40 eyes used cells from patients' healthy eyes to repair their diseased eyes.
In a third study, Dr. Tsai used cells from cadaver eyes to engineer immature corneal precursor cells; approximately half of 54 transplants in this study were successful. A later study reported successful transplants of corneal epithelial precursor cells in 60 of 90 patients in Taipei.
Patients in the study had unilateral corneal disease. Specimens were taken from the healthy contralateral eye, and after the epithelial cells were cultured and expanded on amniotic membrane, they were transplanted onto the denuded corneal surface of the damaged eye. Patients first underwent a superficial keratectomy to remove any fibrovascular ingrowth.
The Taipei patients achieved complete re-epithelialization of the corneal surface within 2 to 4 days. At 1 month the corneal epithelium had covered the ocular surface. Finger counting visual acuity increased to 20/200 in one patient who had preoperatively had total corneal opacification. During the follow-up, no patient had re current neovascularization or inflammation in the eye that received the transplant.
Future directions
Neurobiologist Evan Snyder, MD, PhD, of Harvard Medical School and Children's Hospital of Boston, has more than 15 years of stem cell research experience. He said one of the determinants for the ease and success of a given stem cell transplantation is the number of cells necessary to produce a functional effect.
"One probably needs fewer cells to cover the cornea than to fit a strobe, for example. The cell cycle of stem cells is approximately 18 hours in a mouse and 36 hours in humans," said Dr. Snyder, whose primary work is with diseases of the nervous system and genetic diseases.
He was asked if he foresees a time when the corneal precursor cell growth cycle will be shortened from its current 2 to 3 weeks. "If growth occurs too quickly it may not follow the normal growth cycle time. Therefore, 2 to 3 weeks for the relatively few number of cells needed in the time frame needed may be just right," he said.
Dr. Snyder described evaluating the source of corneal precursor cells. "The more immature the cells are, the quicker they will grow, but the first question this raises is will you have to keep going back to harvest immature cells or are they immortal? Our goal is to go once to the source and grow stem cells as a stable cell line as a renewable resource," he said.
"Within 1 to 2 years we will know more about the stem cell growth cycle. We will have a better understanding of cell division and immune compatibility, which may lead to the de-escalation of ethical and political issues surrounding stem cells," Dr. Snyder said. He emphasized that stem cell transplantation is "not a routine intervention, and is still a research issue in which we are looking critically at its safety and efficacy."
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For Your Information:
- Ivan Schwab, MD, can be reached at the University of California-Davis, 4860 Y St., Ste. 2400, Sacramento, CA 95817; (916) 734-6070; fax: (916) 734-6992.
- Ray Jui-Fang Tsai, MD, can be reached at Chang Gung Memorial Hospital, Dept. of Ophthalmology, 2nd Floor, 350 Section 4, Cheng Kung Rd., Taipei, 114, Taiwan; (886) 3-328-1200 ext 8671; fax: (886) 3-328-7798.
- Evan Snyder, MD, PhD, can be reached at Children's Hospital of Boston, 300 Longwood Ave., Rm. 248 Enders, Boston, MA 02115; (617) 355-8577; fax: (617) 738-1542.