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      Three-Dimensional Cell Culture: A Breakthrough in Vivo

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          Abstract

          Cell culture is an important tool for biological research. Two-dimensional cell culture has been used for some time now, but growing cells in flat layers on plastic surfaces does not accurately model the in vivo state. As compared to the two-dimensional case, the three-dimensional (3D) cell culture allows biological cells to grow or interact with their surroundings in all three dimensions thanks to an artificial environment. Cells grown in a 3D model have proven to be more physiologically relevant and showed improvements in several studies of biological mechanisms like: cell number monitoring, viability, morphology, proliferation, differentiation, response to stimuli, migration and invasion of tumor cells into surrounding tissues, angiogenesis stimulation and immune system evasion, drug metabolism, gene expression and protein synthesis, general cell function and in vivo relevance. 3D culture models succeed thanks to technological advances, including materials science, cell biology and bioreactor design.

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          Most cited references21

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          Capturing complex 3D tissue physiology in vitro.

          The emergence of tissue engineering raises new possibilities for the study of complex physiological and pathophysiological processes in vitro. Many tools are now available to create 3D tissue models in vitro, but the blueprints for what to make have been slower to arrive. We discuss here some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment, and the methods for implementing them. We emphasize applications that involve epithelial tissues for which 3D models could explain mechanisms of disease or aid in drug development.
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            Recent advances in three-dimensional multicellular spheroid culture for biomedical research.

            Many types of mammalian cells can aggregate and differentiate into 3-D multicellular spheroids when cultured in suspension or a nonadhesive environment. Compared to conventional monolayer cultures, multicellular spheroids resemble real tissues better in terms of structural and functional properties. Multicellular spheroids formed by transformed cells are widely used as avascular tumor models for metastasis and invasion research and for therapeutic screening. Many primary or progenitor cells on the other hand, show significantly enhanced viability and functional performance when grown as spheroids. Multicellular spheroids in this aspect are ideal building units for tissue reconstruction. Here we review the current understanding of multicellular spheroid formation mechanisms, their biomedical applications, and recent advances in spheroid culture, manipulation, and analysis techniques.
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              Progress and opportunities for tissue-engineered skin.

              Tissue-engineered skin is now a reality. For patients with extensive full-thickness burns, laboratory expansion of skin cells to achieve barrier function can make the difference between life and death, and it was this acute need that drove the initiation of tissue engineering in the 1980s. A much larger group of patients have ulcers resistant to conventional healing, and treatments using cultured skin cells have been devised to restart the wound-healing process. In the laboratory, the use of tissue-engineered skin provides insight into the behaviour of skin cells in healthy skin and in diseases such as vitiligo, melanoma, psoriasis and blistering disorders.
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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
                11 March 2015
                March 2015
                : 16
                : 3
                : 5517-5527
                Affiliations
                [1 ]Radiotherapy Department, Paul Strauss Cancer Center, 3, rue de la Porte de l’Hôpital, 67065 Strasbourg Cedex, France; E-Mail: gnoel@ 123456strasbourg.unicancer.fr
                [2 ]Radiobiology Laboratory, EA 3430, Strasbourg University, Paul Strauss Cancer Center, 3, rue de la Porte de l’Hôpital, 67065 Strasbourg Cedex, France; E-Mails: hburckel@ 123456strasbourg.unicancer.fr (H.B.); ejosset@ 123456strasbourg.unicancer.fr (E.J.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: dantoni@ 123456strasbourg.unicancer.fr ; Tel.: +33-388-252-478; Fax: +33-388-258-508.
                Article
                ijms-16-05517
                10.3390/ijms16035517
                4394490
                25768338
                87928cb3-e670-4e09-8bda-75959c550cb3
                © 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
                : 17 December 2014
                : 05 March 2015
                Categories
                Review

                Molecular biology
                cell culture,three-dimensional cell culture,in vivo
                Molecular biology
                cell culture, three-dimensional cell culture, in vivo

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