Organoids help bridge gap between laboratory study and animal modeling of disease

WINSTON-SALEM, NC — Aug. 6, 2020 — Scientists at the Wake Forest Institute for Regenerative Medicine (WFIRM) have biofabricated human colorectal cancer miniature organs, called organoids, to better understand how a tumor grows in its natural microenvironment and its response to therapies. This new study is the first to replicate observations of native tumor tissue in a laboratory model and validate it in the context of the whole-body physiology.

Current strategies to understand tumor progression studies are centered on the tumor cells in isolation, but do not capture the interactions between a tumor and its surrounding microenvironment. This leads to inaccuracies in predicting tumor progression and chemotherapy response.

“Tumors are products of their environment. They send signals that can have significant effects on local tissue, and they receive signals from nearby cells and tissues that can alter their progression,” said Shay Soker, PhD, senior author of a new study published in the journal Scientific Reports.

New technologies that better show the specific properties of a tumor will have a significant effect on patient death rates and lead to development of new treatments which target the cancer, sparing healthy tissue from the side effects of chemotherapy treatments.

The WFIRM team previously developed a 3D organoid model of the colon, complete with its unique micro-architecture, and used it to analyze colorectal cancer biopsies to identify significant changes in the miroenvironment.

The team analyzed the tumor microenvironment and corresponding “finger print” and found that samples with orderly extracellular matrix – the “glue” that holds cells together – maintained these structures. In contrast, disordered extracellular matrix allowed for a more primitive “finger print.” Furthermore, these results were replicated in the context of whole-body physiology, to show for the first time that a pre-structured tumor microenvironment maintains its architecture in the laboratory. Non-traditional treatments that target the extracellular matrix might provide valuable avenues for developing new treatments or therapies that synergize with existing chemotherapeutic or radiation technologies.

By controlling cancer cell responsiveness through changes to the tumor microenvironment, lower doses of chemotherapy or radiation could become effective, thereby reducing or eliminating many of the undesirable side effects of traditional cancer therapies, as well as yielding lower tumor resistance.

“The 3D bioengineered colon cancer constructs are a promising model for drug development and screening because they can reproduce human physiology at a high level,” said Anthony Atala, MD, director of WFIRM.

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Additional co-authors include: Mahesh Devarasetty, Anthony Dominijanni, Samuel Herberg, Ethan Shelkey, and Aleksander Skardal. Authors Soker and Skardal are inventors on patent rights related to this work owned by Wake Forest University Health Sciences. The patents, whose value may be affected by publication, have the potential to generate royalty income in which the inventors would share.

The work was supported with funding through the NIH NCI grant R33CA202822. The authors wish to acknowledge the support of the Wake Forest Baptist Comprehensive Cancer Center Tumor Tissue and Pathology Shared Resource supported by the National Cancer Institute’s Cancer Center Support Grant award number P30CA012197.

About the Wake Forest Institute for Regenerative Medicine: The Wake Forest Institute for Regenerative Medicine is recognized as an international leader in translating scientific discovery into clinical therapies, with many world firsts, including the development and implantation of the first engineered organ in a patient. Over 400 people at the institute, the largest in the world, work on more than 40 different tissues and organs. A number of the basic principles of tissue engineering and regenerative medicine were first developed at the institute. WFIRM researchers have successfully engineered replacement tissues and organs in all four categories – flat structures, tubular tissues, hollow organs and solid organs – and 15 different applications of cell/tissue therapy technologies, such as skin, urethras, cartilage, bladders, muscle, kidney, and vaginal organs, have been successfully used in human patients. The institute, which is part of Wake Forest School of Medicine, is located in the Innovation Quarter in downtown Winston-Salem, NC, and is driven by the urgent needs of patients. The institute is making a global difference in regenerative medicine through collaborations with over 400 entities and institutions worldwide, through its government, academic and industry partnerships, its start-up entities, and through major initiatives in breakthrough technologies, such as tissue engineering, cell therapies, diagnostics, drug discovery, biomanufacturing, nanotechnology, gene editing and 3D printing.

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Bonnie Davis
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http://dx.doi.org/10.1038/s41598-020-66785-1

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