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      Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications

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          Abstract

          The skin is the largest organ of the body and has an array of functions. Skin compartments, epidermis, and hair follicles house stem cells that are indispensable for skin homeostasis and regeneration. These stem cells also contribute to wound repair, resulting in restoration of tissue integrity and function of damaged tissue. Unsuccessful wound healing processes often lead to non-healing wounds. Chronic wounds are caused by depletion of stem cells and a variety of other cellular and molecular mechanisms, many of which are still poorly understood. Current chronic wound therapies are limited, so the search to develop better therapeutic strategies is ongoing. Adult stem cells are gaining recognition as potential candidates for numerous skin pathologies. In this review, we will discuss epidermal and other stem cells present in the skin, and highlight some of the therapeutic applications of epidermal stem cells and other adult stem cells as tools for cell/scaffold-based therapies for non-healing wounds and other skin disorders. We will also discuss emerging concepts and offer some perspectives on how skin tissue-engineered products can be optimized to provide efficacious therapy in cutaneous repair and regeneration.

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          Most cited references140

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          The recent discovery of microRNAs (miRNAs) took many by surprise because of their unorthodox features and widespread functions. These tiny, approximately 22-nucleotide, RNAs control several pathways including developmental timing, haematopoiesis, organogenesis, apoptosis, cell proliferation and possibly even tumorigenesis. Among the most pressing questions regarding this unusual class of regulatory miRNA-encoding genes is how miRNAs are produced in cells and how the genes themselves are controlled by various regulatory networks.
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            Generation of induced pluripotent stem cells using recombinant proteins.

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              Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis.

              Inconsistent with the view that hair follicle stem cells reside in the matrix area of the hair bulb, we found that label-retaining cells exist exclusively in the bulge area of the mouse hair follicle. The bulge consists of a subpopulation of outer root sheath cells located in the midportion of the follicle at the arrector pili muscle attachment site. Keratinocytes in the bulge area are relatively undifferentiated ultrastructurally. They are normally slow cycling, but can be stimulated to proliferate transiently by TPA. Located in a well-protected and nourished environment, these cells mark the lower end of the "permanent" portion of the follicle. Our findings, plus a reevaluation of the literature, suggest that follicular stem cells reside in the bulge region, instead of the lower bulb. This new view provides insights into hair cycle control and the possible involvement of hair follicle stem cells in skin carcinogenesis.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                23 October 2015
                October 2015
                : 16
                : 10
                : 25476-25501
                Affiliations
                [1 ]Faculty of Medical Sciences, the University of the West Indies, Cave Hill Campus, P.O. Box 64, Bridgetown BB 11000, St. Michael, Barbados; E-Mail: nkemcho.ojeh@ 123456cavehill.uwi.edu
                [2 ]Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami Miller Medical School, 1600 NW 10th Avenue, RMSB, Room 2023-A, Miami, FL 33136, USA; E-Mails: ipastar@ 123456med.miami.edu (I.P.); mtcanic@ 123456med.miami.edu (M.T.-C.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: ostojadinovic@ 123456med.miami.edu ; Tel.: +1-305-243-7295; Fax: +1-305-243-6191.
                Article
                ijms-16-25476
                10.3390/ijms161025476
                4632811
                26512657
                9d533874-87ce-4295-90c8-04a1352db460
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 September 2015
                : 20 October 2015
                Categories
                Review

                Molecular biology
                skin,epidermis,stem cells,wound healing,chronic wounds
                Molecular biology
                skin, epidermis, stem cells, wound healing, chronic wounds

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