WASHINGTON, Oct. 30, 2017 /PRNewswire/ -- The latest issues of Experimental Biology and Medicine (Volume 242, Issues 16 and 17, October and November, 2017) highlight recent advances in microphysiological systems (MPS). The issues were guest edited by Dr. John P. Wikswo, founding Director of the Vanderbilt Institute for Integrative Biosystems Research and Education in Nashville, TN, and contain 15 articles by scientists and engineers from the National Institutes of Health (NIH), the IQ Consortium, the Food and Drug Administration and Environmental Protection Agency, industry and academia. Topics include the progress, challenges and future of organs-on-chips, dissemination of tissue chips into Pharma, children's health protection, liver zonation, liver chips and their coupling to interconnected systems, gastrointestinal MPS, maturation of immature cardiomyocytes in a heart-on-a-chip, co-culture of multiple cell types in a human skin construct, use of synthetic hydrogels to create engineered organoids that form neural tissue models, the blood-brain barrier-on-a-chip, MPS models of coupled female reproductive organs, coupling MPS devices to create a body-on-a-chip and the use of a microformulator to recapitulate endocrine circadian rhythms.
As noted in the introductory review by Dr. David E. Watson (Senior Research Advisor at Eli Lilly and Company), Dr. Rosemarie Hunziker (Tissue Engineering/Regenerative Medicine Program Director, National Institute of Biomedical Imaging and Bioengineering) and Dr. Wikswo, MPS, which include engineered organoids, single organ/tissue chips and multiple organs interconnected to create miniature in vitro models of human physiological systems, are rapidly becoming effective tools for drug development and the mechanistic understanding of tissue physiology and pathophysiology. After five years of vigorous funding by DARPA, NIH and DTRA, the resulting device and technique development has demonstrated that human MPS models can provide new capabilities for in vitro recapitulation of normal and diseased human tissue interfaces and three-dimensional tissues. Three areas of application that readily suggest MPS approaches include disease biology/pharmacology; absorption, distribution, metabolism and excretion (ADME)-pharmacokinetic clinical pharmacology; and systems toxicology.
For example, using human skin constructs as a tool in drug development is described in the paper from Dr. Angela Christiano's group at Columbia University. Co-author Dr. Hasan Erbil Abaci explains, "Many medical conditions and side effects of drugs manifest themselves through skin symptoms, which makes [skin] a very important organ for drug testing. It was actually one of the first engineered tissues, and was initially only composed of two cell types back in the 1980s. Those pioneering studies back then started the first wave of skin tissue engineering, and now, nearly 40 years later, we are generating and witnessing the second wave of skin tissue engineering with the emerging iPS cell technology that allowed us to make many different skin cell types, and the recent microfabrication tools such as 3D bioprinting. Using these new biotechnology and engineering tools now, we are becoming more capable of incorporating many critical skin components in these engineered skin constructs, such as vasculature, immunity, pigmentation, sensory neurons and even skin appendages like hair follicles. It is to our great excitement to see the advancements also in generating other tissues and how our skin constructs will communicate with those when integrated on microfluidic platforms to mimic human physiology."
Dr. Michael L. Shuler, Samuel B. Eckert Professor of Engineering at Cornell University, says, "The dramatic increases in research on microphysiological systems have led not only to significant advances in the underlying science, but a tremendous increase in industrial relevance. We are seeing many companies beginning to use microphysiological systems, particularly multi-organ or body-on-a-chip systems, which is a tremendous advance in the last three years. The next three years will be critical in determining if industry will incorporate these systems into their normal processes of drug development. If these systems work well they should significantly reduce the costs of drugs to the public while making more useful drugs available."
Dr. Kristin Fabre of AstraZeneca concurs: "As the former National Center for Advancing Translational Science Tissue Chip Program Manager, I worked directly with many MPS developers and could clearly see the potential impact this technology could have on disease modeling and therapeutic development. Now, we have the exciting opportunity to identify and test MPS platforms to determine if they can help us accelerate potentially more effective treatments for patients with an even better safety profile. The technology is still relatively new, and there is much to be done to gain confidence and general acceptance in these models. Therefore, key partnerships with government, academia and industry will continue to be essential to ensure that MPS are a robust, viable, user-friendly commercial product."
Areas that may be beyond the state of today's MPS include fully functioning adaptive immune models and recapitulation of the complete metastatic cascade, but progress is being made in these directions. MPS studies are now moving from isolated organ experiments to coupled in vitro organ systems. There is a concomitant increase in the complexity of the support hardware and an opportunity for systems multi-omics to identify the signatures of both disease and drug response. Ultimately, MPS tissues may include self-organizing tissue heterogeneity and hierarchical microvasculature. At no point, however, should the goal be to create perfect "microhumans" – instead, the most effective use of MPS technologies will be to produce toy models that are optimized for the particular application, as demonstrated by the work described in this issue.
Dr. Joanna Burdette, Associate Professor of Medicinal Chemistry and Pharmacognosy at the University of Illinois at Chicago, agrees: "Microphysiological systems are starting to redefine biology and provide new methods for preclinical drug testing. Our next challenge is to develop accurate disease models. The community is highly collaborative, which facilitates creative design and rapid scientific advances."
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said "Microphysiological systems or Organs-on-a-Chip have developed from a powerful convergence of technologies which will allow better understanding of both normal and pathophysiology. Furthermore, it will allow future testing of every type of therapeutic in a meaningful model of human organ function. I am extremely pleased with the high quality of all of the articles in this important EBM Thematic Issue and thank Dr. John Wikswo and all of the authors."
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