Innovation and Partnerships Office

Tracking and Quantifying Organization of Epithelial Cells IB-2903

APPLICATIONS OF TECHNOLOGY:

  • Drug development
  • Toxicology testing
  • Regenerative medicine
  • Cancer research

ADVANTAGES:

  • Quantifiable assessments
  • Simple scalable platform using inexpensive materials
  • Permits sustained observation of rare cell populations
  • Supports replicable experiments
  • Provides controlled environment to study dynamic intercellular relationships

ABSTRACT:

Berkeley Lab researchers have developed a new technology that, for the first time, can track and quantify the dynamic self-organization of cells that build epithelial tissues such as mammary glands. Their discovery provides valuable information about the effect of various molecules on the organization of epithelial cells, where disorganization can lead to cancers of the breast, prostate, sweat glands, lung, and skin.

A team led by Mina Bissell and Mark LaBarge developed a technique to build arrays of cylindrical microwells into which various human epithelial cells are seeded and may subsequently organize themselves into bilayered structures. A classic model tissue architecture supported by the platform and protocols employs luminal epithelial cells (LEPs), which can secrete milk and myoepithelial cells (MEPs) that contract and naturally surround LEPs to form ductile secretory glands.

Once the LEPs and MEPs are installed in the microwells, they can be exposed to a wide variety of proteins, hormones, drug candidates, or chemical substances — singly or in combination — and the effects on self-organization of the bilayered ductile tissue can be measured. Each well confines cell growth within a space of 100 microns in diameter at a depth of 50 microns and is formed in a substrate of pliable materials such as polydimethylsiloxane or agaroses that more closely resemble biological substrates than hard plastic.

The assay will be an effective tool for regenerative medicine researchers studying self-organization in adult and embryonic tissues and for drug developers exploring the effects of candidate pharmaceuticals on organization in human tissues. The tool will be useful for research that is unraveling how normal tissue organization is maintained and lost in a bilayered epithelium such as the mammary gland or prostate, and it may shed light on the factors that go awry and lead to cellular disorganization in cancers and other diseases. The assay can also be used to evaluate the effects of potentially hazardous chemicals in the environment, to study how cells interact with other cells in the presence of these substances.

DEVELOPMENT STAGE: Bench-scale prototype

STATUS: Patent pending. Available for licensing or collaborative research.

FOR MORE INFORMATION:

Chanson, L, Brownfield, D., Garbe, J.C., Kuhn, I., Stampfer, M.R., Bissell, M.J., LaBarge, M.A., “Self-Organization is a Dynamic and Lineage-intrinsic Property of Mammary Epithelial Cells,” Proceedings of the National Academy of Sciences, Vol. 108, No. 8, pp.3264-3269, 2011.

Yarris, Lynn. “Getting Organized: Berkeley Lab Study Shows How Breast Cell Communities organize into Breast Tissue,” Berkeley Lab News Center, March 11, 2011.
http://newscenter.lbl.gov/feature-stories/2011/03/11/getting-organized-breast-cell-communities-organize-into-breast-tissue/

SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:

Long-term Growth of Finite Life Span Normal Human Epithelial Cells, IB-2077

Microenvironment Arrays for Tissue-Specific Functional Screening of Compounds, IB-3237

REFERENCE NUMBER: IB-2903