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Isolation and Characterization of Multipotent Skin-Derived Precursors from Human Skin

^a Departments of Developmental Biology and
^b Urology, Hospital for Sick Children, Toronto, Ontario, Canada;
^c Departments of Physiology and
^d Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada;
^e Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada

Key Words. Neural stem cells • Neural crest • Neurons • Schwann cells • Smooth muscle cells • Foreskin • Stem cells • Dermis

Correspondence: Freda D. Miller, Ph.D., Senior Scientist and Professor, Department of Developmental Biology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. Telephone: 416-813-7654, ext. 1434; Fax: 416-813-2212; e-mail: fredam{at}sickkids.ca

We have previously isolated, expanded, and characterized a multipotent precursor cell from mammalian dermis (termed skin-derived precursors [SKPs]) that can differentiate into both neural and mesodermal progeny. In this study, we report the isolation, expansion, and characterization of a similar precursor cell from neonatal human foreskin tissue. Like their rodent counterparts, human SKPs grew in suspension as spheres in the presence of the mitogens fibroblast growth factor 2 and epidermal growth factor and expressed nestin, fibronectin, vimentin, and characteristic embryonic transcription factors. Human SKPs could be maintained in culture for long periods of time and would still differentiate into neurons, glia, and smooth muscle cells, including cells with the phenotype of peripheral neurons and Schwann cells. Clonal analysis indicated that single SKP cells were multipotent and could give rise to all of these progeny. Moreover, human SKPs apparently derive from an endogenous precursor within human foreskin; a subpopulation of dissociated primary foreskin cells could differentiate into neurons, a cell type never seen in skin, and the initial spheres to develop from skin expressed the same markers and had the same potential as do passaged SKPs. Together, these data indicate that SKPs are an endogenous multipotent precursor cell present in human skin that can be isolated and expanded and differentiate into both neural and mesodermal cell types.

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