Journal Article

Allogeneic Ex Vivo Expanded Corneal Epithelial Stem Cell Transplantation: A Randomized Controlled Clinical Trial

Turner, Marc L., Dhillon, Baljean, Kaye, Stephen, Ramaesh, Kanna, Campbell, John D.M., Fraser, Alasdair R., Ahmad, Sajjad, Barry, Jacqueline, Agrawal, Ashish, Downing, Ian, Bienek, Carol, Drain, John, Mantry, Sanjay, Glover, Alison, Nerurkar, Louis, Hargreaves, Emily, Mcgowan, Neil W.A., Pelly, Jane, MacDonald, Margaret, Atkinson, Anne, MacRury, Coral, Cuthbertson, Bruce

2019

Overview

Limbal stem cell deficiency (LSCD) is a disease resulting from the loss or dysfunction of epithelial stem cells, which seriously impairs sight. Autologous limbal stem cell transplantation is effective in unilateral or partial bilateral disease but not applicable in total bilateral disease. An allogeneic source of transplantable cells for use in total bilateral disease can be obtained from culture of donated cadaveric corneal tissue. We performed a controlled multicenter study to examine the feasibility, safety, and efficacy of allogeneic corneal epithelial stem cells in the treatment of bilateral LSCD. Patients were randomized to receive corneal epithelial stem cells cultured on amniotic membrane (AM): investigational medicinal product (IMP) or control AM only. Patients received systemic immunosuppression. Primary endpoints were safety and visual acuity, secondary endpoint was change in composite ocular surface score (OSS). Sixteen patients were treated and 13 patients completed all assessments. Safety was demonstrated and 9/13 patients had improved visual acuity scores at the end of the trial, with no significant differences between IMP and control groups. Patients in the IMP arm demonstrated significant, sustained improvement in OSS, whereas those in the control arm did not. Serum cytokine levels were measured during and after the period of immune suppression and we identified strongly elevated levels of CXCL8 in the serum of patients with aniridia, which persisted throughout the trial. This first randomized control trial of allogeneic corneal epithelial stem cells in severe bilateral LSCD demonstrates the feasibility and safety of this approach. Stem Cells Translational Medicine 2019;8:323–331 Patients with severe ocular surface disorder received transplants of amniotic membrane with (black bars) or without (gray bars) cadaveric‐donor‐derived cultured limbal stem cells. All patients received immune suppression. Only patients who received transplants containing limbal stem cells showed sustained significant improvements (reductions) in combined ocular surface scores (5 factors scored 0–3 where 0 is a normal eye score).

• Publisher: John Wiley & Sons, Inc,Oxford University Press
• Subject: Acuity / Adult / Aged / Allogeneic corneal epithelial stem cell transplantation / Amnion - cytology / Amnion - surgery / Amniotic membrane / Aniridia / Autografts / Cadavers / Cell culture / Clinical trials / Cloning / Cornea / Cornea - cytology / Cornea - surgery / Corneal Diseases - surgery / Corneal Transplantation - methods / Donation of organs, tissues, etc / Epithelial Cells - cytology / Epithelium, Corneal - cytology / Feasibility studies / Female / Good Manufacturing Practice / Hematopoietic Stem Cell Transplantation - methods / Human Clinical / Humans / Immunosuppression / Immunotherapy / Limbal stem cell deficiency / Limbus Corneae - cytology / Limbus Corneae - surgery / Male / Middle Aged / Ocular surface disorders / Patients / Safety / Single-Blind Method / Stem cell transplantation / Stem Cell Transplantation - methods / Stem cells / Stem Cells - cytology / Studies / Transplantation / Transplantation, Autologous - methods / Transplants & implants / Visual Acuity - physiology / Young Adult