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Organs on Chips: Human Disease Models
Drug development is an extremely expensive, long and relatively inefficient process, often hampered by the lack of appropriate (human) disease model systems. Assays based on primary tissues and cells in culture dishes are often difficult to reproduce from cell batch to cell batch and in general do not behave like cells in complex multicellular organs as in the human body. In addition, ethnic and other genetic differences that influence disease pathophysiology, drug sensitivity and toxicity (side effects) between individuals are not captured by inbred animal models commonly used in laboratories. In addition, there is increasing social, ethical and financial pressure to reduce, refine and replace animal use for drug development and safety pharmacology. Clearly, there is a social and scientific need for in vitro alternatives for currently used model systems that more accurately model human disease and pathophysiology. In particular models that reproduce complex, integrated organ-level human physiological and pathological responses would be of great value.
The solution could be provided by the development of “Organs on Chips”, multicellular mini-organs grown in a microfluidic chips that in vitro reproduce complex, integrated organ-level physiological and pathological responses of humans. To grow, maintain, and analyze representative human organ tissue in vitro, it is necessary to create the appropriate microenvironment in which biochemical, physical, and geometrical factors are controlled with high spatiotemporal precision. Among the likely solutions to this is microfluidics technology that can produce “chips” in which small volumes of liquids can be precisely controlled and moved through microscopic (micrometer and millimeter-sized) channels and chambers, much like blood flows through the body, creating a microenvironment in which “mini-organs” can grow, function, and interact similar to the in vivo situation. If the cell types required to create Organs- on- Chips are derived from human stem or progenitor cells, expressing genes associated with specific diseases, in combination with microfluidics technology this provides an innovative approach to generating reproducible and scalable models for healthy and diseased human tissue, based on defined genetic backgrounds.
The main objective of this workshop is to develop a common view on the required combinations of methods and technologies for creating “Organs-on-Chips” for different organs and diseases, on the basis of state of the art keynote lectures and active multidisciplinary discussions. The workshop will be informal and highly interdisciplinary with delegates from diverse fields, among which physicists, chemists, engineers, biologists, medical specialists (oncologists, pathologists), representatives from pharmaceutical research, in-vitro-diagnostics (IVD) companies, and a representative from the US regulatory authorities. The following major themes will be addressed in the workshop: (1) Organs-on-Chips – definition and purpose; (2) Different human cell sources: opportunities; (3) Microfluidics / microfabrication / tissue engineering approaches; (4) Applications, regulatory aspects and related issues.
The results of the workshop will be summarized in a meeting report, to be published in a high impact scientific journal.