Isolation of multipotent neural crest-derived stem cells from the adult mouse cornea

¹ Cornea Center, Tokyo Dental College, Chiba, Japan; Department of Opthalmology, Keio University School of Medicine, Tokyo, Japan
² Department of Physiology, Keio University School of Medicine, Tokyo, Japan
³ Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo, Japan

^* To whom correspondence should be addressed. E-mail: shige{at}sc.itc.keio.ac.jp.

	Abstract

We report the presence of neural crest-derived corneal precursors (COPs) that initiate spheres by clonal expansion from a single cell. COPs expressed the stem cell markers, nestin, Notch1, Musashi-1, ABCG2 and showed the side-population (SP) cell phenotype. COPs were multipotent with the ability to differentiate into adipocytes, chondrocytes as well as neural cells, as shown by the expression of III-tubulin, GFAP and neurofilament-M. COP spheres prepared from E/nestin-EGFP mice showed induction of EGFP expression that was not originally observed in the cornea, indicating activation of the neural-specific nestin 2nd intronic enhancer in culture. COPs were Sca-1+, CD34+, CD45- and c-kit-. Numerous GFP+ cells were observed in the corneas of mice transplanted with whole bone marrow of transgenic mice ubiquitously expressing GFP, however, no GFP+ COP spheres were initiated from these mice. On the other hand, COP spheres from transgenic mice encoding P0- Cre/Floxed-EGFP as well as Wnt1-Cre/Floxed-EGFP were GFP+ indicating the neural crest origin of COPs, which was confirmed by the expression of the embryonic neural crest markers Twist, Snail, Slug, and Sox9. Taken together, these data indicate of existence of neural crest-derived, multipotent stem cells in the adult cornea.

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