3D model systems go mainstream for drug testing: Rocky Tuan explains

Posted by Biome on 11th August 2014 - 1 Comment


Co-Editor-in-Chief of Stem Cell Research & Therapy Rocky Tuan discusses the road to developing 3D microphysiological systems for testing drug toxicity and efficacy, following a supplement in Stem Cell Research & Therapy from leading researchers involved in the US National Institutes of Health Microphysiological Systems program.

 

Experimental model systems have long served an important role in biomedical research – to gain fundamental insights into biological mechanisms and pathways, to test the effects of putative therapies, and to detect potential toxicities of chemicals and unknown agents.

Human microvessels network developed using a microfluidic platform. Image source: Moya et al, Stem Cell Research & Therapy, 2013, 4(Suppl 1):S15.

Human microvessels network developed using a microfluidic platform. Image source: Moya et al, Stem Cell Research & Therapy, 2013, 4(Suppl 1):S15.

Organismal models constituted early attempts, while advances in tissue and cell culture systems, first developed in early 20th century, have ushered in more defined and analytical laboratory-based approaches that permit more in-depth studies of cellular and molecular events. These systems generally utilize culture vessels consisting of confined, two-dimensional ceramic or polymeric substrates for cell growth, which provide convenience in handling, imaging, and monitoring. Although these systems have yielded a tremendous wealth of information and knowledge on biological processes, they are fundamentally deficient in modeling physiological processes in whole organisms, because of the lack of three-dimensional tissue architecture and multi-organ tissue interactions. In contrast, animal models such as rats and rabbits, that are commonly used in drug toxicity or efficacy screens, are not complete human physiological mimics, and thus often fail to faithfully reproduce complex biological interactions and pathways or predict potential harmful or beneficial effects. A paradigm shift has thus been emerging in recent years to develop more robust, physiologically relevant model systems.

Recognizing this need, the United States National Institutes of Health (NIH), in partnership with the US Defense Advanced Research Projects Agency (DARPA) and the US Food and Drug Agency (FDA), initiated a Microphysiological Systems (MPS) Program in 2012, to accelerate the development of human MPS that will improve the reliability to identify human drug toxicities and predict the potential efficacy of a drug in a human population prior to use of the drug in late-stage clinical studies. The goal of the NIH MPS Program is to create and integrate MPS that utilize human primary or stem cell sources, which are sustainable over a four week period and functionally represent the ten major organ systems: circulatory, respiratory, integumentary, reproductive, endocrine, gastrointestinal, nervous, urinary, musculoskeletal, and immune.

Top: Microphysiological device for ex vivo modelling of kidney function. Bottom: Primary human renal epithelial cells cultured in the device. Image source: Kelly et al, Stem Cell Research & Therapy, 2013, 4(Suppl 1):S17.

Top: Microphysiological device for ex vivo modelling of kidney function. Bottom: Primary human renal epithelial cells cultured in the device. Image source: Kelly et al, Stem Cell Research & Therapy, 2013, 4(Suppl 1):S17.

In the 2013 Supplement of Stem Cell Research and Therapy, titled Stem Cells on Bioengineered Microphysiological Platforms for Disease Modeling and Drug Testing, the 19 investigators currently involved in the NIH MPS contributed mini-review articles describing advances in their respective systems, providing an exciting overview of the potential of the MPS approach in modeling biological systems and activities.  This consortium of research activities represents interests from 15 Institutes/Centers of the NIH.  The topics covered include experimental models for neurovascular systems, kidney, liver, myocardiac tissues, metastatic processes, osteochondral tissue, muscle, lung, intestine, brain, and skin. The cell sources employed range from adult mesenchymal stem cells, various tissue progenitor cells, embryonic stem cells, and induced pluripotent stem cells, utilizing state-of-the-art microfluidic, mechanoactive, and imaging-compatible microbioreactors.

This funding initiative represents an exciting development in the biomedical research landscape, as it represents the first time that a consortial approach, with substantive, targeted federal funding support, is taken to synergize multi-disciplinary and multi-system platforms. The objective, as stated in the MPS Program is to achieve an interactive, ‘plug-and-play’, multi-tissue platform that faithfully represents human physiology. Three-dimensional ‘tissue-on-a-chip’ (perhaps best coined as ‘Homo chipiens’) promises to present a new and rewarding experimental paradigm to the understanding of human biology and disease pathogenesis, and development of effective disease modifying therapies.

 

The complete list of supplement articles:

Stem cells on bioengineered microphysiological platforms for disease modeling and drug testing

 

 

More about the author(s)

Rocky Tuan, Director, Center for Cellular and Molecular Engineering, University of Pittsburgh, USA.

Rocky Tuan, Director, Center for Cellular and Molecular Engineering, University of Pittsburgh, USA.

Rocky Tuan is Director of the Center for Cellular and Molecular Engineering, and the Center for Military Medicine Research, at the University of Pittsburgh, USA, where he is also Professor and Executive Vice Chair in the Department of Orthopaedic Surgery, Associate Director of the McGowan Institute for Regenerative Medicine, and Professor in the Departments of Bioengineering and Mechanical Engineering & Materials Science. He obtained his PhD from Rockefeller University, USA, and pursued his postdoctoral research at Harvard Medical School. Tuan was then appointed Assistant Professor in the Department of Biology at the University of Pennsylvania in Philadelphia, where he would go on to become Associate Professor. He later joined Thomas Jefferson University, USA, as Director of Orthopaedic Research and Professor and Vice Chairman in the Department of Orthopaedic Surgery. Tuan then moved to the National Institutes of Health (NIH) National Institute of Arthritis, and Musculoskeletal and Skin Diseases (NIAMS), where he was Chief of Cartilage Biology and Orthopaedics. His current research focusses on orthopaedics, specifically the development, growth, function, and health of musculoskeletal tissues, and the development of technologies to regenerate and/or restore function to diseased and damaged skeletal tissues.

  • Ray Shay

    I don’t think this is good as it seems as the cellular architecture is really in 2d (at best) and not three dimensions. Hence the finding or work has limited relevance