Repairing the corneal epithelium using limbal stem cells or alternative cell-based therapies

ABSTRACT

Introduction: The corneal epithelium is maintained by limbal stem cells (LSCs) that reside in the basal epithelial layer of the tissue surrounding the cornea termed the limbus. Loss of LSCs results in limbal stem cell deficiency (LSCD) that can cause severe visual impairment. Patients with partial LSCD may respond to conservative therapies designed to rehabilitate the remaining LSCs. However, if these conservative approaches fail or, if complete loss of LSCs occurs, transplantation of LSCs or their alternatives is the only option. While a number of clinical studies utilizing diverse surgical and cell culture techniques have shown favorable results, a universal cure for LSCD is still not available. Knowledge of the potential risks and benefits of current approaches, and development of new technologies, is essential for further improvement of LSCD therapies.

Areas covered: This review focuses on cell-based LSCD treatment approaches ranging from current available clinical therapies to preclinical studies of novel promising applications.

Expert opinion: Improved understanding of LSC identity and development of LSC expansion methods will influence the evolution of successful LSCD therapies. Ultimately, future controlled clinical studies enabling direct comparison of the diverse employed approaches will help to identify the most effective treatment strategies.

KEYWORDS:

• Limbal stem cells
• limbal stem cell deficiency
• ABCB5
• CLET
• SLET
• SEAM

Article highlights

• Limbal stem cell deficiency (LSCD) resulting from diverse genetic or acquired conditions is a major cause of corneal blindness.

• Unilateral LSCD can be treated with autologous limbal stem cell (LSC)-containing grafts using various techniques.

• Currently, treatment of patients with bilateral LSCD relies of allogeneic donor cell grafts requiring immunosuppression.

• Alternative therapeutic strategies utilizing stem cells derived from other tissues are currently being tested in preclinical studies.

• ABCB5-positive LSC represent a novel molecularly defined stem cell population with promising therapeutic potential.

This box summarizes key points contained in the article.

Declaration of interest

M.H. Frank, B.R. Ksander and N.Y. Frank are inventors or co-inventors of US and international patents assigned to Brigham and Women’s Hospital, and/or Boston Children’s Hospital, and/or Massachsetts Eye and Ear Infirmary, and/or VA Boston Healthcare System, Boston, MA, licensed to Ticeba GmbH (Heidelberg, Germany) and Rheacell GmbH & Co. KG (Heidelberg, Germany). M.H. Frank. serves as a scientific advisor to Ticeba GmbH and Rheacell GmbH & Co. KG. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by a National Institutes of Health (NIH)/National Eye Institute (NEI) grant RO1EY025794-01A1 grant to NY Frank, BR Ksander and MH Frank, and a by NIH/NEI Schepens Core Grant P30EY003790 to BR Ksander. It was also supported by Veterans Affairs (VA) Rehabilitation Research and Development (RR&D) Merit Review Award 1I01RX000989 and a Harvard Stem Cell Institute (HSCI) seed grant award to NY Frank. Support was also received via the Kanae Foundation for the Promotion of Medical Science (Tokyo, Japan), Alcon Japan Ltd. (Tokyo, Japan) and Japan Eye Bank Association (Tokyo, Japan) to Y Sasamoto.