Biomedical Engineering Reference
In-Depth Information
12.
Biotech Histochem
. 2010 Aug;
85(4):213-29. Tissue engineered
tumor models. Ingram M, Techy
GB, Ward BR, Imam SA,
Atkinson R, Ho H, Taylor CR.
Huntington Medical Research
Institutes, 99 North El Molino
Avenue, Pasadena, CA
91101-1830.
Many research programs use well-characterized
tumor cell lines as tumor models for in vitro studies.
Because tumor cells grown as three-dimensional (3D)
structures have been shown to behave more like
tumors in vivo than do cells growing in monolayer
culture, a growing number of investigators now use
tumor cell spheroids as models. Single-cell-type
spheroids, however, do not model the stromal-
epithelial interactions that have an important role in
controlling tumor growth and development in vivo.
We describe here a method for generating,
reproducibly, more realistic 3D tumor models that
contain both stromal and malignant epithelial cells
with an architecture that closely resembles that of
tumor microlesions in vivo. Because they are so
tissue-like, we refer to them as tumor histoids. They
can be generated reproducibly in substantial
quantities. The bioreactor developed to generate
histoid constructs is described and illustrated. It
accommodates disposable culture chambers that
have filled volumes of either 10 or 64 mL, each
culture yielding on the order of 100 or 600 histoid
particles, respectively. Each particle is a few tenths of
a millimeter in diameter. Examples of histological
sections of tumor histoids representing cancers of
breast, prostate, colon, pancreas, and urinary bladder
are presented. Potential applications of tumor
histoids include, but are not limited to, use as
surrogate tumors for prescreening antisolid tumor
pharmaceutical agents, as reference specimens for
immunostaining in the surgical pathology laboratory,
and use in studies of invasive properties of cells or
other aspects of tumor development and progression.
Histoids containing nonmalignant cells also may
have potential as “seeds” in tissue engineering. For
drug testing, histoids probably will have to meet
certain criteria of size and tumor cell content. Using a
COPAS Plus flow cytometer, histoids containing
fluorescent tumor cells were analyzed successfully
and sorted using such criteria.
