Jump to main content
Jump to site search

Issue 12, 2009
Previous Article Next Article

Engineering microscale cellular niches for three-dimensional multicellular co-cultures

Author affiliations

Abstract

Modeling the in vivo microenvironment typically involves placing cells in a three-dimensional (3D) extracellular matrix (ECM) in physiologically relevant context with respect to other cells. The mechanical and chemical features of 3D microenvironments play important roles in tissue engineering, tumor growth and metastasis, and in defining stem cell niches, and it is increasingly recognized that cells behave much differently when surrounded by a 3D ECM than when anchored to a 2D substrate. To create microenvironments that more closely mimic in vivo settings, here we describe a novel microfluidic device that allows multiple discrete constructs of 3D cell-laden hydrogels to be patterned in a sequence of simple steps. The microfluidic platform allows for real-time imaging of the interactions between multiple cell types exposed to both autocrine and paracrine signaling molecules, all within a 3D ECM environment. Detailed modeling determined that surface tension, hydrophobic interactions, and spatial geometry were important factors in containing the gels within distinct separate channels during the filling process. This allowed us to pattern multiple gel types side-by-side and pattern 3D gels spatially with tight dimensional control. Cells embedded in gels could be patterned by culturing MDA-MB-231 metastatic breast cancer cells and RAW 264.1 macrophage cells within distinct collagen type I and Matrigel ECM environments, respectively. Over a 7 day culture experiment, RAW cells invaded into neighboring gels containing MDA-MB-231 cells, but not into gels lacking cells. These studies demonstrate the versatility and potential of this new microfluidic platform to engineer 3D microscale architectures to investigate cell–cell and cell–matrix interactions.

Graphical abstract: Engineering microscale cellular niches for three-dimensional multicellular co-cultures

Back to tab navigation
Please wait while Download options loads

Supplementary files

Publication details

The article was received on 20 Oct 2008, accepted on 20 Feb 2009 and first published on 18 Mar 2009


Article type: Paper
DOI: 10.1039/B818401A
Citation: Lab Chip, 2009,9, 1740-1748
  •   Request permissions

    Engineering microscale cellular niches for three-dimensional multicellular co-cultures

    C. P. Huang, J. Lu, H. Seon, A. P. Lee, L. A. Flanagan, H. Kim, A. J. Putnam and N. L. Jeon, Lab Chip, 2009, 9, 1740
    DOI: 10.1039/B818401A

Search articles by author