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Capturing complex 3D tissue physiology in vitro

Capturing complex 3D tissue physiology in vitro Over the past two decades, the field of tissue engineering has focused primarily on the creation of tissues for patients. The emphasis of the field is now shifting to include the creation of complex in vitro tissue models that help to explain disease processes (for example, breast cancer) and serve as tools to assess the safety and efficacy of therapies (for example, screens of liver toxicity). The 3D extracellular-matrix (ECM) environment in vivo provides both chemical and physical cues to regulate cell behaviour, serving not only as a structural support, but as a depot of many effector molecules. New synthetic matrices that include well-defined adhesion, growth factor and degradation moieties are being developed to mimic these cues, thereby allowing the quantitative analysis of cell migration, differentiation, survival and growth. Gradients of nutrients and effector molecules are present in 3D cultures. The magnitude of gradients for vital molecules such as oxygen can be predicted for a given experimental arrangement, but data are just emerging for the rates of production and consumption of growth factors, cytokines and other effector molecules. All tissues are subjected to mechanical forces that arise from interstitial flow and tissue movement. These mechanical forces can redistribute effector molecules that are secreted by cells, resulting in the coupling of chemical and mechanical signalling. Microfabrication methods that have been adapted from the microelectronics industry and applied to miniaturize biochemical analyses are now being applied to create complex 3D tissue structures for in vitro studies, and are being combined with microfluidic pumps that can provide microscale fluid flows through tissues for long-term culture. Experimental systems must be developed hand-in-hand with mathematical models that take into account the integration of numerous cues that influence downstream signals and, ultimately, cell responses. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Reviews Molecular Cell Biology Springer Journals

Capturing complex 3D tissue physiology in vitro

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References (145)

Publisher
Springer Journals
Copyright
Copyright © 2006 by Nature Publishing Group
Subject
Life Sciences; Life Sciences, general; Cell Biology; Cancer Research; Developmental Biology; Stem Cells; Biochemistry, general
ISSN
1471-0072
eISSN
1471-0080
DOI
10.1038/nrm1858
Publisher site
See Article on Publisher Site

Abstract

Over the past two decades, the field of tissue engineering has focused primarily on the creation of tissues for patients. The emphasis of the field is now shifting to include the creation of complex in vitro tissue models that help to explain disease processes (for example, breast cancer) and serve as tools to assess the safety and efficacy of therapies (for example, screens of liver toxicity). The 3D extracellular-matrix (ECM) environment in vivo provides both chemical and physical cues to regulate cell behaviour, serving not only as a structural support, but as a depot of many effector molecules. New synthetic matrices that include well-defined adhesion, growth factor and degradation moieties are being developed to mimic these cues, thereby allowing the quantitative analysis of cell migration, differentiation, survival and growth. Gradients of nutrients and effector molecules are present in 3D cultures. The magnitude of gradients for vital molecules such as oxygen can be predicted for a given experimental arrangement, but data are just emerging for the rates of production and consumption of growth factors, cytokines and other effector molecules. All tissues are subjected to mechanical forces that arise from interstitial flow and tissue movement. These mechanical forces can redistribute effector molecules that are secreted by cells, resulting in the coupling of chemical and mechanical signalling. Microfabrication methods that have been adapted from the microelectronics industry and applied to miniaturize biochemical analyses are now being applied to create complex 3D tissue structures for in vitro studies, and are being combined with microfluidic pumps that can provide microscale fluid flows through tissues for long-term culture. Experimental systems must be developed hand-in-hand with mathematical models that take into account the integration of numerous cues that influence downstream signals and, ultimately, cell responses.

Journal

Nature Reviews Molecular Cell Biology – Springer Journals

Published: Mar 1, 2006

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