Screened at the symposium opening, this animation artistically connects concepts of therapeutic organ engineering presented during the event. Credit: Wyss Institute at Harvard University
th Annual Wyss International Symposium held on September 22 nd focused on Therapeutic Organ Engineering. By bringing together world-leading experts in this highly multi-disciplinary biomedical research area, the event galvanized recent advances in different key disciplines that impact present and may guide future synergistic approaches aiming to create transplantable organs in the laboratory.
The event was opened by Wyss Institute Founding Director Donald Ingber to a large, international audience from academia, clinical institutions and industry who learned about breakthroughs and new visions presented in 12 captivating presentations and a closing plenary session. Organized by Ingber and Wyss Institute faculty members David Mooney, Jennifer Lewis, Christopher Chen and Ali Khademhosseini, the speakers addressed key challenges and presented synthetic solutions integrating stem cell biology, new biomaterials, 3D organ engineering and regenerative medicine approaches.
According to Ingber who summarized the event, “this field still is embryonic, but the range of contributions we have heard about today is huge. There is enormous potential here and we need to sew many of the approaches together and understand the shortest path to ultimately get organ replacements to patients.”
1/17 Wyss Core Faculty member David Mooney presented a new biomaterials approach which his team is developing in collaboration with David Scadden from Harvard University, and which increases the success rates of bone marrow transplants in irradiated mice. The approach could be developed as an enhancement for human bone marrow therapy in leukemia and other patients. Credit: Wyss Institute at Harvard University 2/17 With the aim to develop organoids, small organ-like structures that are created in in vitro culture, towards better disease modeling and regenerative medicine opportunities, Matthias Lutolf from the Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland, outlined a fascinating series of materials and microfluidic approaches. Lutolf’s work is focused on providing defined geometrical environments for intestinal organoid formation, reducing unwanted heterogeneity in their cell compositions, and engineering tubular, perfusable systems that can be exposed to a microbiome. Credit: Wyss Institute at Harvard University 3/17 Founding Wyss Core Faculty member Kevin Kit Parker, whose vision is the engineering of complete, functional heart valves, summarized insights into how single cardiomyocytes mechanically couple to each other, how the contractile molecular fibers in heart tissue can align themselves in parallel patterns, and how biomechanic and cellular principles from contracting jellyfish and stingray can inspire tissue engineering solutions for constructing human muscular heart pumps. Credit: Institute at Harvard University 4/17 Wyss Institute Founding Director Donald Ingber with Wyss Core Faculty member Jennifer Lewis. Along with Wyss Institute faculty members David Mooney, Chris Chen and Ali Khademhosseini, Ingber and Lewis organized the symposium. Credit: Institute at Harvard University. 5/17 Wyss Core faculty member Jennifer Lewis highlighted her team’s efforts aimed at reconstructing human kidney tissue. Using intricate 3D printing techniques creating vascularized kidney tissue from different cell types, her group has recreated some of the kidney’s principle filtration and reabsorption abilities. Credit: Wyss Institute at Harvard University 6/17 Kristi Anseth, an expert in designing new materials for organ and tissue engineering from the University of Colorado at Boulder addressed the challenge of creating dynamic tissue environments, essentially introducing the fourth dimension — time — in the design of extracellular matrix materials that primary cells can live on and be controlled in their behavior over time. Credit: Wyss Institute at Harvard University 7/17 Scott Hollister from the Georgia Institute of Technology made the point that implantable regenerative devices, like a 3D printed tracheal splint, can promote natural-like tissue growth and prevent the collapse of bronchiolar airways in patients with a condition called Tracheobronchomalacia. His group is now developing patient-specific vascularized 3D-printed scaffold approaches for other regenerative processes in the human body. Credit: Wyss Institute at Harvard University 8/17 Scott Hollister, Milica Radisic, Kristi Anseth and Chris Chen in the event auditorium. Credit: Wyss Institute at Harvard University 9/17 After summarizing previous approaches to engineering 3D-printed vascular networks in vitro and showing how they can connect to host vasculature of animal models in vivo, Christopher Chen shared with the audience translational efforts where this and similar strategies helped re-vascularize ischemic sites resulting from infarct and vascular leg occlusion. Chris also presented an endothelium-driven regenerative method to treat liver injury, which he has developed in collaboration with Sangeeta Bhatia at MIT. Credit: Wyss Institute at Harvard University 10/17 Nenad Bursac from Duke University described the engineering of macrotissues called ‘cardiopatches’ from human pluripotent stem cells for treatment of myocardial infarction and ischemic heart disease. The artificial tissue patches mature mechanically, molecularly and electrically and display heart muscle functionality. They can be prevascularized to increase integration with host tissue and electrical coupling with heart tissue in animal models. Credit: Wyss Institute at Harvard University 11/17 University of Toronto’s Milica Radisic, also a pioneer in cardiac tissue engineering, outlined ‘Biowire’, a platform that facilitates the maturation of human pluripotent stem cell-derived cardiomyocytes. The electrically matured cardiomyocytes and other cell types were integrated into microfluidic vascularized ‘angiochips’ for advanced drug testing and discovery purposes. Radisic also presented new methods to surgically apply engineered tissue patches to injured tissues. Credit: Wyss Institute at Harvard University 12/17 Nenad Bursac, Chris Chen and Wyss Institute visiting scholar James Gorman. Credit: Wyss Institute at Harvard University 13/17 Wyss Associate Faculty Ali Khademhosseini spoke about biomaterials emerging from his lab, that, like the tunable tropoelastin-based MeTro hydrogels, can be used as super-elastic materials in tissue engineering and surgical sealing applications, or, like minimally invasive shear-thinning biomaterial (STB) gels, help to occlude damaged blood vessels. Credit: Wyss Institute at Harvard University 14/17 Ali Khasemhosseini, Michael Levin, Laura Niklason and Jennifer Elisseeff. Credit: Wyss Institute at Harvard University 15/17 Jennifer Elisseeff from Johns Hopkins University has been developing ways with which ECM-mimicking hydrogels can be combined with developmental processes. Her talk covered a wide range of topics ranging from hydrogel effects in the repair of microfractures to designer biomaterials that can be applied as soft tissue fillers. Elisseeff conveyed to the audience that immune cells are among the first responders to implanted biomaterials and that they help shape not only the regenerative microenvironment, but also systemic immunological changes. Skewing these immune cell activities with functionalized biomaterials thus could lead to improved tissue regeneration. Credit: Wyss Institute at Harvard University 16/17 Wyss Associate Faculty member Michael Levin from Tufts University impressed the concept of ‘bioelectronics’ on the audience. He made clear that in non-neuronal tissues, ion channel-targeting drugs or genetic manipulations can specifically alter electric activities, changing tissue plasticity, and bringing bioelectric approaches into the realm of tissue regeneration in higher organisms including humans. Credit: Wyss Institute at Harvard University 17/17 The symposium’s plenary talk was presented by Laura Niklason from Yale University, who first summarized the state-of-the-art of cell therapies and then honed in on impressive approaches to engineer implantable trachea-stents and “universal” arteries that have been progressing through preclinical trials, with latter being tested in human trials. Credit: Wyss Institute at Harvard University