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First published online September 27, 2007
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Submitted on April 17, 2007
Accepted on September 14, 2007

TISSUE-SPECIFIC STEM CELLS

A Highly Enriched Niche of Precursor Cells with Neuronal and Glial Potential within the Hair Follicle Dermal Papilla of Adult Skin

David PJ Hunt 1*, Paul N Morris 2, Jane Sterling 3, Jane Anderson 1, Alexis Joannides 1, Colin Jahoda 4, Alastair Compston 1, Siddharthan Chandran 1

1 Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, UK
2 Department of Plastic and Reconstructive Surgery, Addenbrookes Hospital, University of Cambridge, Cambridge, UK
3 Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
4 Centre for Stem Cell Biology and Regenerative Medicine, School of Biological Sciences, University of Durham, UK

* To whom correspondence should be addressed. E-mail: dpjh2{at}cam.ac.uk.


  Abstract

Skin-derived precursor cells (SKPs) are multipotent neural crest-related stem cells which grow as self-renewing spheres and are capable of generating neurons and myelinating glial cells. SKPs are of clinical interest because they are accessible and potentially autologous. However, although spheres can be readily isolated from embryonic and neonatal skin, SKP frequency falls away sharply in adulthood and primary sphere generation from adult human skin is more problematic. In addition the culture-initiating cell population is undefined and heterogeneous, limiting experimental studies addressing important aspects of these cells such as the behaviour of endogenous precursors in vivo and the molecular mechanisms of neural generation.

Using a combined fate-mapping and microdissection approach, we have identified and characterised a highly enriched niche of neural crest-derived sphere-forming cells within the dermal papilla of the hair follicle of adult skin. We demonstrate that the dermal papilla of the rodent vibrissal follicle is 1000-fold enriched for sphere forming neural crest-derived cells compared to whole facial skin. These "papillaspheres" share a similar phenotypic and developmental profile to SKPs, can be readily expanded in vitro and are able to generate both neuronal and glial cells in response to appropriate cues.

We demonstrate that papillaspheres can be efficiently generated and expanded from adult human facial skin by microdissection of a single hair follicle. This strategy of targeting a highly enriched niche of sphere-forming cells provides a novel and efficient method for generating neuronal and glial cells from an accessible adult somatic source which is both defined and minimally invasive.

 Key Words. Skin-derived precursor, Dermal Papilla, Hair follicle, Adult stem cell, Neural repair




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