How does cultured limbal stem cell transplantation play into the current practical use of stem cells for corneal regeneration?

Cultured limbal stem cell transplantation is a milestone in corneal reconstruction.

I have been involved in the exciting scientific adventure of cultivating and transplanting limbal stem cells from the beginning. I believe, and have experienced personally, that this is one of the most important discoveries in corneal surgery.

Paolo Rama

Step by step we have reached the goal of making the procedure reproducible and standardized.

Biology is the basis, and the way cells are cultivated is critical to the success of the treatment. Many of those who have claimed relatively poor results might have used cells that were cultivated inappropriately.

Another key to success is doing accurate patient selection, preparation and close monitoring after surgery to detect and proactively treat any sign of infection, inflammation and dry eye. If healthy stem cells are implanted on a bad surface, they lose their potential to re-create a healthy cornea.

Patients need close, individual attention because every case is different and responds in a different way to the treatment. In addition, in a number of these patients, the damage involves not only the limbus, but also the eyelids, the conjunctiva and the tear apparatus. In such cases, restoring limbal function is only one stage of a complex strategy of ocular surface reconstruction, which may involve several surgical interventions.

Paolo Rama, MD, is head of the ophthalmology department of San Raffaele Hospital in Milan.

Massimo Busin

Cultured limbal stem cell transplantation holds no advantages compared with other techniques.

Provided that there is a sufficiently large portion of healthy limbus in the contralateral eye, I do not see the advantages of implanting autologous cultured cells rather than doing auto-limbal transplantation. The costs involved are high; a cultured limbal sheet costs around €10,000. No wonder, since the procedure is extremely time-consuming: back and forth between the operating theater and the laboratory, involving surgeons, lab technicians, biologists, drivers, as well as the use of expensive biological materials and sophisticated equipments.

Implanted cells do work, but using them is like taking a much longer, more difficult, tortuous route rather than go down a straight, easier way to get where you need.

Auto-limbal grafts have the additional advantage of transplanting a portion of conjunctiva, which in most cases is necessary to restore the ocular surface. Healthy corneal and conjunctival stem cells work synergistically to reconstruct the surface.

I have performed many auto-limbal transplants with a high rate of success. Cultured stem cell transplantation is an exciting idea from a purely scientific point of view, but has little substance when we come to clinical practice.

When both eyes are severely damaged, as in the case of chemical burns, the only treatment that initially seemed to work was the allogenic transplantation of stem cells. However, DNA analysis conducted by Sheraz Daya, MD, on eyes in which this method was used showed that no donor stem cell DNA was present in the site of the implant 1 to 3 years after the procedure, in spite of prolonged immunosuppressive therapy. The rate of failure is extremely high, and unfortunately there is very little that can be done in these cases.

Massimo Busin, MD, is head of the ophthalmology department of Villa Serena Hospital in Forlì, Italy.