Human stem cells for organs-on-chips: “clinical trials” without patients?

ABSTRACT An exciting multidisciplinary area of scientific research has recently emerged around a new concept now referred to as “organ-on-a-chip.” “Organ” is, of course, clear and “chip” is familiar to many as the miniaturized electrical circuitry in their mobile phone or laptop, but organ-on-a-chip? The term was coined to describe a cell culture based model system in which cells of different kinds are placed on small structures (chips), usually made of synthetic polymers, that had been “patterned” into grooves, channels, or spirals using the same kind of technology used for making electrical chips. These chip and cell combinations can mimic (or model) the smallest functional subunit of an organ or tissue. Using organs-on-chips, it is becoming possible to mimic many organs and tissues in the human body but in a miniaturized format outside the body. Depending on the cell types used and the format of the patterning on the chip, the alveoli of a lung, small numbers of synchronously contracting heart cells, or even mini kidney and liver-like structures can be created. By adding bacteria, immune cells, drugs, or even cells from diseased tissue to the chips, it may even be possible to model human disease states, not only reducing the use of experimental animals for research but also providing better ways of looking for cures for human ailments. In this chapter we will explain what making organs-on-chips entails, what role human stem cells could play in making organs-on-chips a success, what the applications could be, and what challenges will be faced in getting there.