Eyeworld

62 | EYEWORLD | OCTOBER 2020 by Ellen Stodola Editorial Co-Director Stem cell transplantation for corneal scarring C SKILL FOCUS ORNEA S tem cell transplantation for corneal scarring is currently in development, with limited experience so far in human patients. Sayan Basu, MBBS, and Ali Djalilian, MD, discussed this treatment and how it works. Before getting into treatment options and choosing a treatment, Dr. Basu discussed some of the key terms, including allogeneic grafts, embryonic stem cells, induced pluripotent stem cells, and limbal stem cell transplantation. He noted that the term allogeneic means from another person. The converse, he said, is autologous, meaning from the same person. "These are terms used to refer to the source of tissue/grafts or organs for transplantation," he explained. Embryonic stem cells (ESCs) are those that are found in the early (embryo) stage of the formation of the fetus. Typically, Dr. Basu said, in the case of human ESCs, these are created in the lab or obtained from fertility clinics as un- used embryos. They have the potential to create any tissue in the body. ESCs have the greatest potential and are pluripotent, however, they are allogeneic. Induced pluripotent stem cells (iPSCs), he said, are adult cells that have been programmed to function similar to ESCs by introducing certain genes, known as the Yamanaka factors or some variations thereof. "Usually these are derived from skin fibroblasts," Dr. Basu said. "Once iPSCs are formed, they can, like ESCs, produce any tissue of the body. The advantage over natural ESCs is that iPSCs are autologous." Limbal stem cells are adult stem cells that are present throughout life and are responsible for producing the corneal epithelial cells. Like the cornea, all epithelial surfaces in the body (like the skin, gastric mucosa, or endometrium) have their own adult stem cells in different locations. Dr. Basu said that this is because epithelial surfaces have a high turnover (cells die and fall off and need to be replaced by new cells), and stem cells keep these surfaces epithe- lialized. However, adult stem cells, unlike iPSCs or ESCs, can only produce cells of one/limited type(s); they can't make all cells and tissues of the body. According to Dr. Basu, the corneal epi- thelial stem cells were discovered at the limbus in the late 1980s, and since then, it has been possible to reverse corneal stem cell damage by transplanting healthy limbal tissue from either the other eye of the same patient (autologous) or another person (allogeneic: living or cadaver- ic). "There are many techniques of limbal stem cell transplantation; the most recent and popu- lar of them is simple limbal epithelial transplan- tation (SLET)," he said. Treatment options now and on the horizon Currently no therapy exists that can reverse a formed scar, Dr. Basu said. Scarring can be mitigated to an extent by treating the cause early and adequately, he added. "If the scar is significantly opaque and interferes with visual function, it has to be removed surgically." This can be done with laser, if the scar is superficial, or by performing a corneal transplantation, if the scar is deep. Surgical therapies include phototherapeutic keratectomy using excimer laser for superficial scars and non-penetrating (DALK) or pene- trating (PK) corneal transplantation for deeper scars, Dr. Basu said. The limbus is also the source of mesenchy- mal stem/stromal cells (MSC), Dr. Basu said. MSCs are of interest for modulating scarless wound healing. He added that there are a large number of trials using MSCs for various kinds of injuries and degenerations. They also have immunomodulatory properties and are less im- munogenic. Therefore, allogeneic therapy is less of a problem with MSCs. They are also known as stromal stem cells, he said. Mesenchymal is a morphological description, while stromal is an anatomical description (based on the location within the tissue). Dr. Basu said there is a lot of interest in using MSCs, either from the limbus or from the bone marrow to treat corneal stromal patholo- gies and opacities. At LV Prasad Eye Institute, continued on page 64 About the doctors Sayan Basu, MBBS Director and D Balasubramanian Chair of Eye Research LV Prasad Eye Institute Hyderabad, India Ali Djalilian, MD Professor of Ophthalmology University of Illinois College of Medicine Chicago, Illinois

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