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TISSUE-SPECIFIC STEM CELLS

Characterization of the Limbal Epithelial Stem Cell Niche: Novel Imaging Techniques Permit In Vivo Observation and Targeted Biopsy of Limbal Epithelial Stem Cells

^aCells for Sight Transplantation and Research Programme,
^bOcular Repair and Regeneration Biology Unit, UCL Institute of Ophthalmology, London, United Kingdom;
^cMoorfields Eye Hospital NHS Foundation Trust, London, United Kingdom

Key Words. Stem cell • Cornea • Limbus cornea • Somatic stem cell biology • Human • Stem cell transplantation • Three-dimensional imaging

Correspondence: Alex J. Shortt, M.Sc., M.R.C.Ophth., MRC Clinical Research Fellow, Institute of Ophthalmology and Moorfields Eye Hospital, 11–43 Bath Street, London, EC1V 9EL, United Kingdom. Telephone: +442076086894; Fax: +442076086887; e-mail: a.shortt{at}ucl.ac.uk

Received September 14, 2006; accepted for publication February 18, 2007.
First published online in STEM CELLS EXPRESS   March 1, 2007.



It is anticipated that stem cell (SC) therapy will enable the regeneration of diseased tissues and organs. Understanding SC niches is an essential step toward realizing this goal. By virtue of its optical transparency and physical separation of SC and transient amplifying cell compartments, the human cornea provides a unique opportunity to visualize and observe a population of adult stem cells, limbal epithelial stem cells (LESCs), in their niche environment. To date, the characteristics of the LESC niche have remained unclear. State-of-the-art imaging techniques were used to construct a three-dimensional (3D) view of the entire human corneal limbus and identify the structural characteristics of the LESC niche. Two distinct candidate LESC niche structures were identified. Cells within these structures express high levels of the putative limbal stem cell markers p63 and ABCG2; however, current methods cannot identify for certain which exact cells within this cell population are truly LESCs. These structures could be located and observed in vivo in normal human subjects, but not in patients with clinically diagnosed corneal LESC deficiency. The distribution of these structures around the corneal circumference is not uniform. Biopsies targeted to limbal regions rich in LESC niche structures yielded significantly higher numbers of LESCs in culture. Our findings demonstrate how adult stem cell niches can be identified and observed in vivo in humans and provide new biological insight into the importance of LESC niche structures in maintaining normal LESC function. Finally, the concept of targeted biopsy of adult SC niches improves stem cell yield and may prove to be essential for the successful development of novel adult stem cell therapies.

Disclosure of potential conflicts of interest is found at the end of this article.