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Trial Provides Impetus for Autologous Limbal Stem Cell Transplantation in Vision Threatening Disease

Review of “Allogeneic Ex Vivo Expanded Corneal Epithelial Stem Cell Transplantation: A Randomized Controlled Clinical Trial” from STEM CELLS Translational Medicine by Stuart P. Atkinson 

Limbal stem cell deficiency results from the loss or dysfunction of corneal epithelial stem cells, which results in reduced vision or blindness and chronic ocular irritation amongst other symptoms [1]. To avoid the somewhat problematic application of large segments of limbal tissue from healthy eyes [2] or donor eyes [3], researchers and clinicians alike have turned to a potentially exciting alternative: the ex vivo expansion of small segments of autologous or allogeneic corneal epithelium on substrates such as amniotic membrane. This strategy produces a cell product rich in stem cells that has been employed to treat approximately eighty patients across nine studies [4], although the combined data generally lacks coherence. Importantly, no allogeneic studies have included a control comparison arm, no multi-center studies have been published, and the contribution of stem cells independent of surgery, amniotic membrane resurfacing, and immunosuppression remains to be determined.

These problems led researchers from the laboratory of John D.M. Campbell (Scottish National Blood Transfusion Service, Edinburgh, UK) to perform a multicenter randomized, controlled, and partially blinded phase I/II trial to examine the feasibility, safety, and efficacy of allogeneic corneal epithelial stem cells cultured on amniotic membrane at good manufacturing practice standard for the treatment of bilateral limbal stem cell deficiency [5]. 

Here are the details on this exciting new trial from the team's recent STEM CELLS Translational Medicine article:

  • Randomized patients with severe bilateral limbal stem cell deficiency received corneal epithelial stem cells derived from deceased donors cultured on amniotic membrane or control amniotic membrane only
    • All patients received systemic immunosuppression and topical autologous serum eye drops
    • In total, the study began with sixteen patients with thirteen completing all assessments
  • A lack of serious adverse reactions or events attributed to the stem cell graft suggests safety
  • Nine of thirteen patients exhibited improved visual acuity scores with no significant differences between the experimental and control groups
  • However, only those patients in the experimental arm displayed significant sustained improvement in composite ocular surface scores
  • Measurements of serum cytokine levels uncovered strongly elevated levels of the pro-inflammatory CXCL8 chemokine in patients with persistent aniridia

Overall, the findings from this first randomized control trial of allogeneic corneal epithelial stem cells in severe bilateral limbal stem cell deficiency demonstrate feasibility and safety and provide the impetus for further studies and trials into this potentially useful approach.

For more on corneal epithelial stem cells and treatment approaches for limbal stem cell deficiency, stay tuned to the Stem Cells Portal!


  1. Ahmad S, Osei-Bempong C, Dana R, et al., The culture and transplantation of human limbal stem cells. Journal of Cellular Physiology 2010;225:15-19.
  2. Keivyon KR and Tseng SCG, Limbal Autograft Transplantation for Ocular Surface Disorders. Ophthalmology 1989;96:709-723.
  3. Tsubota K, Satake Y, Kaido M, et al., Treatment of Severe Ocular-Surface Disorders with Corneal Epithelial Stem-Cell Transplantation. New England Journal of Medicine 1999;340:1697-1703.
  4. Behaegel J, Ni Dhubhghaill S, Koppen C, et al., Safety of Cultivated Limbal Epithelial Stem Cell Transplantation for Human Corneal Regeneration. Stem Cells International 2017;Article ID 6978253:11.
  5. Campbell JDM, Ahmad S, Agrawal A, et al., Allogeneic Ex Vivo Expanded Corneal Epithelial Stem Cell Transplantation: A Randomized Controlled Clinical Trial. STEM CELLS Translational Medicine 2019;8:323-331.