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An Eye for an Eye: Long Term Clinical Success with Limbal Stem Cells

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From Nature

The long term success of limbal stem cell (LSC) therapy to treat blindness has been highlighted in an article from Nature News & Views. LSCs reside in the narrow zone between the cornea and conjunctiva and are essential for corneal clarity and the efficient transmission and focus of light onto the retina. However ocular burns or infection can deplete LSCs, causing limbal stem cell deficiency (LSCD). Subsequent conjunctival cell invasion forms an epithelial layer over the cornea leading to corneal vascularisation, inflammation, stromal scarring and blindness. There are 8 million new cases worldwide of this painful, blinding disease each year. A recent article published in the New England Journal of Medicine by Pellegrini, De Luca and colleagues1 reports the successful treatment of LSCD following corneal burn by treatment of the affected eye with LSCs taken from the healthy, neighbouring eye. This follows the success of the first reported clinical trial of this therapy last year at the North East England Stem Cell Institute (NESCI) in Newcastle (UK), where eight patients with LSCD were treated using their own limbal stem cells, without the need for immunosuppression.2 This technique, first developed by Pellegrini’s group in 1997,3 was modified by the Newcastle group to be completely animal free by expanding patients limbal stem cells on human amniotic membrane2 instead of mouse 3T3 cells used in the original study.1,3 In all patients LSCD was successfully reversed with significant improvement in visual acuity and corneal capacity over the 19 month trial period. Pellegrini, De Luca and colleagues1 now report the results of their impressive study of 112 patients with LSCD with a follow-up of up to 10 years, which demonstrates the permanent reconstitution of healthy, self-renewing corneal epithelium in 78% of patients. Further, the authors found that treatment with limbal cultures in which p63-bright cells constituted more than 3% of colony forming cells was associated with the best clinical outcome. This work not only provides further evidence for the long term viability and success of this treatment, but equips clinicians with a powerful diagnostic tool to predict the long term transplant outcome in patients receiving autologous LSC grafts.

References

1. Rama P, Matuska S, Paganoni G et al., Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med. 2010 363(2):147-55.

2. Kolli S, Ahmad S, Lako M, Figueiredo F. Successful clinical implementation of corneal epithelial stem cell therapy for treatment of unilateral limbal stem cell deficiency. Stem Cells. 2010 28(3):597-610.

3. Pellegrini G, Traverso CE, Franzi AT et al., Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet. 1997 349(9057):990-3.

Also see related items from The Times and Newcastle University.