Porous polymer scaffolds fabricated to support the growth of
biological tissue for implantation may hold the potential to greatly accelerate
the development of cancer therapeutics.
Researchers at Rice University and the University of Texas
MD Anderson Cancer Center in Houston and Mount Sinai Medical Center in New York
reported this week that three-dimensional scaffolds used to culture Ewing’s
sarcoma cells were effective at mimicking the environment in which such tumours
Their research appears online in the Proceedings of the National Academy of Sciences.
How the scaffolds
“The scaffolds better recapitulate the microenvironment in
which tumours grow, as compared with two-dimensional plastic surfaces typically
used in cancer research to test anti-cancer drugs,” said Rice bioengineer
Antonios Mikos, who led the research team with Joseph Ludwig, an assistant
professor and sarcoma medical oncologist at MD Anderson.
“We’ve been working to investigate how we can leverage our
expertise in engineering normal tissues to cancerous tissues, which can
potentially serve as a better predictor of anti-cancer drug response than
standard drug-testing platforms,” Mikos said.
By growing cancer cells within a three-dimensional scaffold
rather than on flat surfaces, the team of researchers found that the cells bore
closer morphological and biochemical resemblance to tumours in the body.
Additionally, engineering tumours that mimic those in vivo offers opportunities
to more accurately evaluate such strategies as chemotherapy or radiation
therapies, he said.
The project “provides a path forward to better evaluate
promising biologically targeted therapies in the preclinical setting,” Ludwig
Scaffolds fabricated in the Mikos’ lab facilitate the
development and growth of new tissue outside the body for subsequent
implantation to replace defective tissues.
What the team found
The team found 3-D scaffolds to be a suitable environment
for growing Ewing’s sarcoma, the second most-common paediatric bone malignancy.
The tumour growth profile and protein expression characteristics were “remarkably
unlike” those in 2-D, Mikos said.
These differences led them to hypothesize that 2-D cultures
may mask the mechanisms by which tumours develop resistance to anti-cancer
therapeutics, and “may lead to erroneous scientific conclusions that complicate
our understanding of cancer biology,” they wrote.
The next challenge is to customize scaffolds to more
accurately match the actual conditions in which these tumours are found. “Tumours
in vivo exist within a complex microenvironment consisting of several other
cell types and extracellular matrix components,” Mikos said. “By taking the
bottom-up approach and incorporating more components to this current model, we
can add layers of complexities to make it increasingly reliable.
“But we believe what we currently have is very promising,”
he said. “If we can build upon these results, we can potentially develop an
excellent predictor of drug efficacy in patients.”
Co-authors are, from Rice, graduate students Eliza Fong and
Emily Burdett; Kurt Kasper, a faculty fellow in bioengineering; and Mary
Farach-Carson, Ralph and Dorothy Looney Professor of Biochemistry and Cell
Biology and vice provost for translational bioscience; from MD Anderson, senior
research scientist Salah-Eddine Lamhamedi-Cherradi, research assistants
Vandhana Ramamoorthy and Brian Menegaz, Department of Pathology Associate
Professor Alexander Lazar, graduate student Deeksha Vishwamitra and Department
of Hematopathology Associate Professor Hesham Amin; and, from Mount Sinai
Center, Assistant Professor Elizabeth Demicco. Mikos is the Louis Calder
Professor of Bioengineering and Chemical and Biomolecular Engineering at Rice.
The National Institutes of Health, a National University of
Singapore-Overseas Graduate Scholarship and an MD Anderson Support Grant
supported the research.