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Scientists successfully transplant bioengineered corneal stem cells into vision impaired patients.

Scientists in the United States and Taiwan have successfully transplanted bioengineered corneal stem cells to restore or improve vision in patients whose corneas had been damaged by disease or injury.

Eyesight was restored or improved in 10 of 14 patients treated at the University of California at Davis Medical Center and in 6 of 6 patients undergoing the new transplant procedure at Chang Gung Memorial Hospital in Taiwan. All of the patients suffered vision loss due to chemical, fire, or radiation burns or autoimmune diseases such as Stevens-Johnson syndrome that result in depletion of the corneal stem cells responsible for repairing ocular surface damage. Because of this deficiency, the patients had failed standard treatments including conventional corneal transplantation, which cannot transfer sufficient stem cells to produce corneal regeneration.

One approach to correcting corneal surface disease due to stem cell deficiency has been to transplant a segment of the stem cell-laden limbus, taken from the patient's contralateral eye or from a living or cadaveric donor. This procedure requires harvesting of at least half of the limbus, however, thus jeopardizing the patient's or living donor's eye. To avoid this potential problem, the researchers developed 2 slightly different techniques for growing donor stem cells in the laboratory.

R. Rivkah Isseroff, MD, professor of dermatology at UC Davis and director of a laboratory that produces bioengineered skin replacements, and Ivan Schwab, MD, professor of ophthalmology, spent 10 years perfecting their procedure, which they described in the July issue of the journal Cornea. It involves removing a few stem cells from a healthy cornea and growing them in culture dishes until they produce a fragile film of corneal cells just one cell thick. At this point, the scientists transfer most of the corneal cells to a matrix of sterile amniotic membrane, freezing and banking the remainder for possible future use. The cells continue to expand on the substrate until the layer is 5-10 cells thick and forms a sturdy composite tissue that combines the elasticity and resilience of amniotic membrane with the biologic properties of corneal tissue. This bioengineered composite tissue then is stitched onto the patient's eye, after the abnormal corneal tissue has been removed.

The procedure developed by Ray Jui-Fang Tsai, MD and colleagues at Chang Gung Memorial Hospital and reported in the July 13 issue of the New England Journal of Medicine is essentially the same except that the scientists directly seed the corneal stem cells onto an amniotic membrane rather than first expanding the cells in laboratory dishes.

Of the 14 patients treated at UC Davis, 4 received transplants of composite tissue grown from cornea cells donated by a sibling or child. All experienced improved or restored eyesight, including a 69-year-old man who had lost most of his vision in a 1973 chemical accident and had subsequently undergone 6 corneal transplants-all failures. None of the donors experienced complications from stem cell harvesting, which the researchers described as a quick and painless procedure. The other 10 UC Davis patients, each of whom had one healthy cornea, received transplants of composite tissue cultivated from corneal stem cells harvested from their good eyes. Six of the 10 had successful outcomes.

All 6 patients at Chang Gung Memorial Hospital received autologous corneal stem cell transplants. "Complete reepithelialization of the corneal surface occurred within 2 to 4 days of transplantation in all 6 eyes receiving transplants," wrote Tsai and co-authors. "By one month, the ocular surface was covered with corneal epithelium, and the clarity of the cornea was improved. In 5 of the 6 treated eyes, the mean visual acuity improved from 20/112 to 20/45. In one patient with a chemical burn who had total pacification of the cornea, acuity improved from the ability to count fingers at 40 cm to 20/200."

Despite the promise of bioengineered corneal surface transplants, a few problems still must be worked-out, Isseroff and Schwab acknowledged in a commentary accompanying the report from Tsai's group. In particular, it can be difficult to identify corneal stem cells and ensure that enough of them are present in the bioengineered tissue to repopulate the ocular surface. "The identification of cell-surface markers, such as those identified for keratinocyte (skin) stem cells, will help address this issue," Isseroff and Schwab said. A second challenge is optimizing the scaffold on which the replacement corneal surface is grown. "Although amniotic membrane (acquired after birth by donation and immunologically nonreactive) is currently the most widely used material for this purpose, a bioengineered laboratory equivalent...would minimize the possible risk, albeit remote, of [infection]."

It is too early to know how long the donor corneal stem cells will persist and whether they will integrate into the limbus of the recipient eye. Furthermore, answering the question of what will happen to the tissue decades after implantation will require years of careful observation and follow-up. But the researchers are optimistic that bioengineered corneal surfaces will become the third type of bioengineered replacement tissue for use in humans-the first 2 being skin and cartilage. And they are optimistic that in the future, the technology will be extended to the lung, gastrointestinal tract, bladder, and other epithelial tissues throughout the body.

"The really exciting thing is where this can take us," said Schwab. "Replacing diseased tissues and even organs with bioengineered tissue is rapidly moving from the realm of science fiction to reality."

Mark Mannis, MD, vice chairman of the department of ophthalmology at UC Davis and editor of Cornea agrees that the techniques developed by US and Taiwanese researchers "represent a significant step forward in bioengineered tissue transplantation and provide a therapeutic alternative to patients who otherwise would have no treatment options." But he cautioned that the leap from a bioengineered corneal surface, consisting of just a few cell layers, to a completely bioengineered cornea or other organ is a large one. The media and particularly the public need to understand that, he said, and to recognize that at this time, the new procedures "are still investigational and are applicable to a very small percentage of patients with vision loss requiring corneal transplant and ocular surface reconstruction."
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Comment:Scientists successfully transplant bioengineered corneal stem cells into vision impaired patients.
Author:Grygotis, Michele
Publication:Transplant News
Article Type:Brief Article
Geographic Code:9TAIW
Date:Jul 29, 2000
Words:1017
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