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      Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Organ replacement regenerative therapy is purported to enable the replacement of organs damaged by disease, injury or aging in the foreseeable future. Here we demonstrate fully functional hair organ regeneration via the intracutaneous transplantation of a bioengineered pelage and vibrissa follicle germ. The pelage and vibrissae are reconstituted with embryonic skin-derived cells and adult vibrissa stem cell region-derived cells, respectively. The bioengineered hair follicle develops the correct structures and forms proper connections with surrounding host tissues such as the epidermis, arrector pili muscle and nerve fibres. The bioengineered follicles also show restored hair cycles and piloerection through the rearrangement of follicular stem cells and their niches. This study thus reveals the potential applications of adult tissue-derived follicular stem cells as a bioengineered organ replacement therapy.

          Abstract

          Bioengineered hair follicles can be produced from embryonic follicle germ cells, but whether these follicles can interact with the surrounding tissue and function normally is unknown. Here, bioengineered hair follicles transplanted into mouse dermis make connections with the surrounding tissue and show normal hair cycles.

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          Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche.

          Cédric Blanpain, William E. Lowry, Andrea Geoghegan … (2004)
          In adult skin, each hair follicle contains a reservoir of stem cells (the bulge), which can be mobilized to regenerate the new follicle with each hair cycle and to reepithelialize epidermis during wound repair. Here we report new methods that permit their clonal analyses and engraftment and demonstrate the two defining features of stem cells, namely self-renewal and multipotency. We also show that, within the bulge, there are two distinct populations, one of which maintains basal lamina contact and temporally precedes the other, which is suprabasal and arises only after the start of the first postnatal hair cycle. This spatial distinction endows them with discrete transcriptional programs, but surprisingly, both populations are growth inhibited in the niche but can self-renew in vitro and make epidermis and hair when grafted. These findings suggest that the niche microenvironment imposes intrinsic "stemness" features without restricting the establishment of epithelial polarity and changes in gene expression.
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            Dominant role of the niche in melanocyte stem-cell fate determination.

            Shin-ichi Nishikawa, Yann Barrandon, Hisahiro Yoshida … (2002)
            Stem cells which have the capacity to self-renew and generate differentiated progeny are thought to be maintained in a specific environment known as a niche. The localization of the niche, however, remains largely obscure for most stem-cell systems. Melanocytes (pigment cells) in hair follicles proliferate and differentiate closely coupled to the hair regeneration cycle. Here we report that stem cells of the melanocyte lineage can be identified, using Dct-lacZ transgenic mice, in the lower permanent portion of mouse hair follicles throughout the hair cycle. It is only the population in this region that fulfils the criteria for stem cells, being immature, slow cycling, self-maintaining and fully competent in regenerating progeny on activation at early anagen (the growing phase of hair follicles). Induction of the re-pigmentation process in K14-steel factor transgenic mice demonstrates that a portion of amplifying stem-cell progeny can migrate out from the niche and retain sufficient self-renewing capability to function as stem cells after repopulation into vacant niches. Our data indicate that the niche has a dominant role in the fate determination of melanocyte stem-cell progeny.
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              The secret life of the hair follicle.

              M. Hardy (1992)
              The mammalian hair follicle is a treasure waiting to be discovered by more molecular geneticists. How can a tiny cluster of apparently uniform epithelial cells, adjacent to a tiny cluster of uniform mesenchymal cells, give rise to five or six concentric cylinders, each of which is composed of cells of a distinctive type that synthesize their own distinctive set of proteins? There is now evidence that several growth factors, cell adhesion molecules and other molecules play important roles in the regulation of this minute organ.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nat Commun
                Journal ID (iso-abbrev): Nat Commun
                Title: Nature Communications
                Publisher: Nature Pub. Group
                ISSN (Electronic): 2041-1723
                Publication date (Electronic): 17 April 2012
                Volume: 3
                Page: 784
                Affiliations
                [1 ]simpleResearch Institute for Science and Technology, Tokyo University of Science , Noda, Chiba 278-8510, Japan.
                [2 ]simpleDepartment of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science , Noda, Chiba 278-8510, Japan.
                [3 ]simpleOrgan Technologies Inc. , Tokyo 101-0048, Japan.
                [4 ]simpleDepartment of Oral Pathology, Showa University School of Dentistry , Tokyo 145-8515, Japan.
                [5 ]simpleTokyo Memorial Clinic , 151-0053, Japan.
                [6 ]simpleDepartment Regenerative Medicine, Plastic and Reconstructive Surgery, Kitasato University School of Medicine, Sagamihara , Kanagawa 252-0374, Japan.
                [7 ]simpleDepartment of Plastic and Aesthetic Surgery, Kitasato University School of Medicine, Sagamihara , Kanagawa 252-0374, Japan.
                Author notes
                Article
                Publisher Item ID: ncomms1784
                DOI: 10.1038/ncomms1784
                PMC ID: 3337983
                PubMed ID: 22510689
                SO-VID: 0c5391d9-40a0-4090-a133-4879c19768c6
                Copyright © Copyright © 2012, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

                History
                Date received : 30 August 2011
                Date accepted : 12 March 2012
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                Subject: Article

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