Open AccessThree-Dimensional Culture Alters Primary Cardiac Cell Phenotype
Author(s) -
Robert E. Akins,
Danielle N. Rockwood,
Karyn G. Robinson,
Daniel Sandusky,
John F. Rabolt,
Christian Pizarro
Publication year - 2010
Publication title -
tissue engineering. part a
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.964
H-Index - 111
eISSN - 1937-335X
pISSN - 1937-3341
DOI - 10.1089/ten.tea.2009.0458
Subject(s) - phenotype , microbiology and biotechnology , biology , stimulation , cell , multicellular organism , cell culture , regenerative medicine , gene expression , function (biology) , cell growth , cell type , heart development , stem cell , endocrinology , gene , genetics , embryonic stem cell
The directed formation of complex three-dimensional (3D) tissue architecture is a fundamental goal in tissue engineering and regenerative medicine. The growth of cells in 3D structures is expected to influence cellular phenotype and function, especially relative cell distribution, expression profiles, and responsiveness to exogenous signals; however, relatively few studies have been carried out to examine the effects of 3D reaggregation on cells from critical target organs, like the heart. Accordingly, we cultured primary cardiac ventricular cells in a 3D model system using a serum-free medium to test the hypothesis that expression profiles, multicellular organizational pathways, tissue maturation markers, and responsiveness to hormone stimulation were significantly altered in stable cell populations grown in 3D versus 2D culture. We found that distinct multi-cellular structures formed in 3D in conjunction with changes in mRNA expression profile, up-regulation of endothelial cell migratory pathways, decreases in the expression of fetal genes (Nppa and Ankrd1), and increased sensitivity to tri-iodothyronine stimulation when compared to parallel 2D cultures comprising the same cell populations. These results indicate that the culture of primary cardiac cells in 3D aggregates leads to physiologically relevant alterations in component cell phenotype consistent with cardiac ventricular tissue formation and maturation.