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Microstructured Cocultures of Cardiac Myocytes and Fibroblasts: A Two-Dimensional In Vitro Model of Cardiac Tissue

Published online by Cambridge University Press:  12 May 2005

Patrizia Camelliti ,
Andrew D. McCulloch  and
Peter Kohl
Patrizia Camelliti
Affiliation:
University Laboratory of Physiology, Oxford, OX1 3PT, UK
Andrew D. McCulloch
Affiliation:
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412, USA
Peter Kohl
Affiliation:
University Laboratory of Physiology, Oxford, OX1 3PT, UK
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Abstract

Cardiac myocytes and fibroblasts are essential elements of myocardial tissue structure and function. In vivo, myocytes constitute the majority of cardiac tissue volume, whereas fibroblasts dominate in numbers. In vitro, cardiac cell cultures are usually designed to exclude fibroblasts, which, because of their maintained proliferative potential, tend to overgrow the myocytes. Recent advances in microstructuring of cultures and cell growth on elastic membranes have greatly enhanced in vitro preservation of tissue properties and offer a novel platform technology for producing more in vivo-like models of myocardium. We used microfluidic techniques to grow two-dimensional structured cardiac tissue models, containing both myocytes and fibroblasts, and characterized cell morphology, distribution, and coupling using immunohistochemical techniques. In vitro findings were compared with in vivo ventricular cyto-architecture. Cardiac myocytes and fibroblasts, cultured on intersecting 30-μm-wide collagen tracks, acquire an in vivo-like phenotype. Their spatial arrangement closely resembles that observed in native tissue: Strands of highly aligned myocytes are surrounded by parallel threads of fibroblasts. In this in vitro system, fibroblasts form contacts with other fibroblasts and myocytes, which can support homogeneous and heterogeneous gap junctional coupling, as observed in vivo. We conclude that structured cocultures of cardiomyocytes and fibroblasts mimic in vivo ventricular tissue organization and provide a novel tool for in vitro research into cardiac electromechanical function.

Keywords

microfluidicsmicropatterningin vivocell culturerabbitrat
Type
Research Article
Information
Microscopy and Microanalysis , Volume 11 , Issue 3 , June 2005 , pp. 249 - 259
Copyright
© 2005 Microscopy Society of America

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