Epidermis generated in vitro: practical considerations and applications

Parenteau, Nancy L.; Nolte, Cynthia J. M.; Bilbo, Patrick; Rosenberg, Mireille; Wilkins, Leon M.; Johnson, Eric W.; Watson, Stephen R.; Mason, Valerie S.; Bell, Eugene

doi:10.1002/jcb.240450304

Cited by 186 publications

(89 citation statements)

References 35 publications

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“…A cultured version of a 'skin equivalent' has been achieved through culturing of keratinocytes either on de-epidermized dermis (Regnier et al, 1981;Watt, 1988;Fartasch and Ponec, 1994) or on collagen gels embedded with dermal fibroblasts (Bell et al, 1981;Regnier et al, 1981;Asselineau and Prunieras, 1984;Asselineau et al, 1985;McCance et al, 1988;Watt, 1988;Coulomb et al, 1989;Fartasch and Ponec, 1994). Such cocultures give rise to stratified epithelium that displays many of the morphological and functional features of an epidermis in vivo (Bell et al, 1981;Kopan et al, 1987;Watt, 1988;Kopan and Fuchs, 1989;Hertle et al, 1991;Parenteau et al, 1991;Fusenig, 1994;Smola et al, 1998).…”

Section: Modeling Organs In Vitro: Organotypic Co-culturesmentioning

confidence: 99%

Modeling tissue-specific signaling and organ function in three dimensions

Schmeichel

Bissell

2003

Journal of Cell Science

537

418

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IntroductionQualitative evaluation of the cellular complexity and structural integrity of organ biopsies has been used by pathologists for decades to gain insight into human diseases. The well-accepted correlation between tissue structure and health or disease conveys important lessons for the development of experimental models for the study of normal human biology and associated disease progression. Optimally, model design should recapitulate both the 3D organization and the differentiated function of any given organ but at the same time allow experimental intervention. By doing so, cell-based models facilitate systematic analyses that address, at the molecular level, how normal organ structure and function are maintained or how the balance is lost in cancer.Because of the ethical, technical and financial constraints inherent in research on human cells and tissues, the demand for models that faithfully parallel human form and function considerably outweighs the supply. We and others asserted more than two decades ago that development of physiologically relevant models of both rodent and human origin should recognize that organs and tissues function in a 3D environment (Elsdale and Bard, 1972;Hay and Dodson, 1973;Bissell, 1981;Ingber and Folkman, 1989). Further, that in the final analysis, the organ itself is the unit of function (Bissell and Hall, 1987). We now know that exposure of cells to the spatial constraints imposed by a 3D milieu determines how cells perceive and interpret biochemical cues from the surrounding microenvironment [e.g. the extracellular matrix, growth factors and neighboring cells (for reviews, see Roskelley et al., 1995;Bissell et al., 2002;Cunha et al., 2002;Ingber, 2002;Radisky et al., 2002)]. Furthermore, it is in this biophysical and biochemical context that cells display bona fide tissue and organ specificity.Here, we describe studies of epithelial-cell-based systems that demonstrate the importance of developing and utilizing 3D human organotypic models to understand the molecular and cellular signaling events underlying human organ biology (Fig. 1). In their most simplistic form, these models comprise homogeneous epithelial cell populations that are cultured within 3D basement-membrane-like matrices. These relatively simple 'monotypic' cell models have progressively evolved into 3D co-culture models containing multiple cell types, which approximate organ structure and function in vitro and enable systematic analyses of the molecular contributions of multiple cell types. Finally, we go on to explore how human 3D culture models are being coupled to existing technologies in the mouse to generate models in vivo that could elucidate the fundamental influence of stromal-epithelial interactions in normal organ function as well as those that perturb organ homeostasis and lead to disease. As a result of these advancements, we are equipped with a hierarchy of related models that appreciate the importance of 3D environments but vary with respect to cellular complexity. By using this collectio...

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Section: Modeling Organs In Vitro: Organotypic Co-culturesmentioning

confidence: 99%

Modeling tissue-specific signaling and organ function in three dimensions

Schmeichel

Bissell

2003

Journal of Cell Science

537

418

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“…As previously described, the collagen gel can be very useful for rapid production of skin substitutes (Bell et al, 1981a;Bell et al, 1981b;Bell et al, 1979) but, the presence of an exogenous scaffold can be disadvantageous for mechanical studies of the extracellular matrix and a severe surface reduction of dermal substitutes can be observed (Auger et al, 1998;Germain and Auger, 1995). Contraction can be prevented using anchorage methods in vitro (Eckes et al, 1995;Germain and Auger, 1995;Grinnell and Lamke, 1984;Parenteau et al, 1991;Xu et al, 1996). However, these anchoraged models are often fragile and difficult to handle.…”

Section: Collagen Gelsmentioning

confidence: 99%

In Vivo and In Vitro Models of Psoriasis

Jean¹,

Pouliot²

2010

Tissue Engineering

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“…2B). To achieve this, keratinocytes can be grown in organotypic culture (Bell et al, 1983;Parenteau et al, 1991). In this system, keratinocytes are cultured at the air-liquid interface on a collagen matrix containing fibroblasts (Fig.…”

Section: ) Ex Vivo Gene Therapymentioning

confidence: 99%

Keratinocyte Gene Transfer and Gene Therapy

Garlick

Fenjves

1996

Critical Reviews in Oral Biology & Medicine

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Gene therapy has moved beyond the pre-clinical stage to the treatment of a variety of inherited and acquired diseases. For such therapy to be successful, genes must be efficiently delivered to target cells and gene products must be expressed for prolonged periods of time without toxic effects to the host. This may be achieved by means of an in vivo strategy where genes are transferred directly into a host cell, or by means of an ex vivo approach through which cells are removed, cultured, targeted for gene delivery, and grafted back to the host. Several obstacles continue to delay safe and effective clinical application of gene therapy in a variety of target cells. The limited survival of transplanted cells, transient expression of transferred genes, and difficulties in targeting stem cells are technical issues requiring further investigation.Epidermal and oral keratinocytes are potential vehicles for gene therapy. Several features of these tissues can be utilized to achieve delivery of therapeutic gene products for local or systemic delivery. These qualities include: (1) the presence of stem cells; (2) the cell-, strata-, and site-specific regulation of keratinocyte gene expression; (3) tissue accessibility; and (4) secretory capacity. Such features can be exploited by the use of gene therapy strategies to facilitate: (1) identification, enrichment, and targeting of stem cells to ensure the continued presence of the transferred gene; (2) high-level and persistent transgene expression using keratinocyte-specific promoters; (3) tissue access needed for culture and grafting for ex vivo therapy and direct in vivo gene transfer; (4) secretion of transgene product for local or systemic delivery; and (5) monitoring of genetically modified tissue and removal if treatment termination is required. Optimal gene therapy strategies are being tested in a variety of tissues to treat dominant and recessive genetic disorders as well as acquired diseases such as neoplasia and infectious disease. This experience provides a basis for the application of such clinical studies to a spectrum of diseases effecting epidermal and oral keratinocytes. Gene therapy is in an early stage yet holds great promise for its ultimate clinical application.

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Epidermis generated in vitro: practical considerations and applications

Cited by 186 publications

References 35 publications

Modeling tissue-specific signaling and organ function in three dimensions

Modeling tissue-specific signaling and organ function in three dimensions

In Vivo and In Vitro Models of Psoriasis

Keratinocyte Gene Transfer and Gene Therapy

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