Stem Cells and Tissue-Engineered Skin

Department of Dermatology, University of California and Veterans Affairs Medical Center, San Francisco, CA, USA.
Skin pharmacology and physiology (Impact Factor: 2.37). 02/2009; 22(2):55-62. DOI: 10.1159/000178864
Source: PubMed


Advances in tissue engineering of skin are needed for clinical applications (as in wound healing and gene therapy) for cutaneous and systemic diseases. In this paper we review the use of epidermal stem cells as a source of cells to improve tissue-engineered skin. We discuss the importance and limitations of epidermal stem cell isolation using biomarkers, in quest of a pure stem cell preparation, as well as the culture conditions necessary to maintain this purity as required for a qualitatively superior and long-lasting engineered skin. Finally, we review the advantages of using additional multipotent stem cell sources to functionally and cosmetically optimize the engineered tissue.


Available from: Ruby Ghadially, May 26, 2015
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    • "Therefore, genetically modified, in vitro-expanded adult stem cells are attractive alternatives for use in gene therapy. In this regard, one previous study demonstrated the formation of clonal units of epidermal structures after infusion of mouse ESCs transduced with retroviruses (Charruyer and Ghadially, 2009). The cell cycle mainly proceeds in three phases, the G0/G1 phase, S phase, and G2/M phase. "
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    ABSTRACT: Epidermal stem cells (ESCs) are characterized as slowcycling, multi-potent, and self-renewing cells that not only maintain somatic homeostasis but also participate in tissue regeneration and repair. To examine the feasibility of adenoviral vector-mediated keratinocyte growth factor (KGF) gene transfer into in vitro-expanded ESCs, ESCs were isolated from samples of human skin, cultured in vitro, and then transfected with recombinant adenovirus (Ad) carrying the human KGF gene (AdKGF) or green fluorescent protein gene (AdGFP). The effects of KGF gene transfer on cell proliferation, cell cycle arrest, cell surface antigen phenotype, and β-catenin expression were investigated. Compared to ESCs transfected with AdGFP, AdKGFtransfected ESCs grew well, maintained a high proliferative capacity in keratinocyte serum-free medium, and expressed high levels of β-catenin. AdKGF infection increased the number of ESCs in the G0/G1 phase and promoted ESCs entry into the G2/M phase, but had no effect on cell surface antigen phenotype (CD49f(+)/CD71(-)). The results suggest that KGF gene transfer can stimulate ESCs to grow and undergo cell division, which can be applied to enhance cutaneous wound healing.
    Moleculer Cells 10/2013; 36(4):316-21. DOI:10.1007/s10059-013-0093-y · 2.09 Impact Factor
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    • "Epidermal stem cells are located in the basal layer of the epidermis and can differentiate into keratinocytes [Blanpain and Fuchs, 2009; Charruyer and Ghadially, 2009]. However, there are relatively few data on the effects of EMF on epidermal stem cells, which are regarded as the progenitor cells of keratinocytes and defined by b1-integrin (known as CD29) þ /CD71 À expression [Barthel and Aberdam, 2005]. "
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    ABSTRACT: To investigate the effects of low frequency electromagnetic fields (EMF) on the proliferation of epidermal stem cells, human epidermal stem cells (hESC) were isolated, expanded ex vivo, and then exposed to a low frequency EMF. The test and control cells were placed under the same environment. The test cells were exposed for 30 min/day to a 5 mT low frequency EMF at 1, 10, and 50 Hz for 3, 5, or 7 days. The effects of low frequency EMF on cell proliferation, cell cycle, and cell-surface antigen phenotype were investigated. Low frequency EMF significantly enhanced the proliferation of hESC in the culture medium in a frequency-dependent manner, with the highest cell proliferation rate at 50 Hz (P < 0.05). Exposure to a low frequency EMF significantly increased the percentage of cells at the S phase of the cell cycle, coupled with a decrease in the percentage of cells in the G1 phase (P < 0.05) but the effect was not frequency dependent. The percentage of CD29(+) /CD71(-) cells remained unchanged in the low frequency EMF-exposed hESC. The results suggested that low frequency EMF influenced hESC proliferation in vitro, and this effect was related to the increased proportion of cells at the S phase. Bioelectromagnetics. © 2012 Wiley Periodicals, Inc.
    Bioelectromagnetics 01/2013; 34(1). DOI:10.1002/bem.21747 · 1.71 Impact Factor
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    • "Sophisticated fabrication and bioengineering techniques have allowed researchers to generate complex three-dimensional environments to regulate stem cell fate. As the physicochemical gradients, matrix components, and surrounding cells constituting stem cell niches in skin are further elucidated (Table 1), tissue engineered systems will need to be increasingly scalable, tunable, and modifiable to mimic these dynamic microenvironments [57–61]. A detailed discussion of different biomaterial techniques for tissue engineering is beyond the scope of this paper, but we refer to reader to several excellent papers on the topic [62–70]. "
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    ABSTRACT: Stem cell-based therapies offer tremendous potential for skin regeneration following injury and disease. Functional stem cell units have been described throughout all layers of human skin and the collective physical and chemical microenvironmental cues that enable this regenerative potential are known as the stem cell niche. Stem cells in the hair follicle bulge, interfollicular epidermis, dermal papillae, and perivascular space have been closely investigated as model systems for niche-driven regeneration. These studies suggest that stem cell strategies for skin engineering must consider the intricate molecular and biologic features of these niches. Innovative biomaterial systems that successfully recapitulate these microenvironments will facilitate progenitor cell-mediated skin repair and regeneration.
    International Journal of Biomaterials 06/2012; 2012(3):926059. DOI:10.1155/2012/926059
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