What are the key similarities and differences between organoids and organs-on-a-chip? What are their advantages and disadvantages, and how widely used are they in practical applications?
Their distinguishing features (already very well-explained in David Belair’s answer) historically stem from the distinction:
Organoids are how biologists build an organ. Organs-on-a-chip are how engineers build an organ.
As you can imagine, the barrier between the two is quite porous (*cough* points to bioengineering in bio *cough*). At the risk of making overly broad generalizations, organoids and organs-on-chips represent different approaches to the question, “What is the fundamental unit of an organ?”
On the biological side, your answer involves many different cell types in contact with one another and their protein matrix, represented with a mass of arrows and acronyms. You know that close-range signaling between different cell types generates vital signals for morphogenesis, differentiation, and survival. Something like this:
On the engineering side, you’re somewhat less interested in what the organ is made of than what it does: transport nutrients from one reservoir to another. You wouldn’t even consider leaving out the blood vessel compartment!
Such different perspectives can lead to organoids and organs-on-a-chip that model the same organ, but look dramatically different from one another.
Those organoids look very intestinal. And it’s impressive that they were grown straight from single cells that self-patterned into blobby crypt-shapes… but one can’t help but notice that there’s no way in or out of those structures. How are you supposed to measure nutrient transfer or permeability? What if you wanted to put a drug or bacteria on the inside? And they’re so randomly shaped and spaced!
On the other hand, look at the precision and spatial control achieved by these organs-on-a-chip! There are four compartments, all easily accessed with liquid or air. It has the unique capacity to apply strain, mimicking peristalsis. But Caco-2 cells (colorectal adenocarcinoma cell line) stuck to a polymer membrane aren’t very much like normal intestine.
Neither approach is strictly better than the other, nor are they mutually exclusive.
- Biologists and engineers have different goals — the biologist builds organs in order to understand how normal organs are built and maintained, while the engineer wants to recapitulate certain organ functions for in vitro tissue models. There’s not a pressing reason drug screens should be done on expensive tissue or stem cell-derived intestinal cells when Caco-2 cells are perfectly serviceable in their own context.
- Biologists and engineers tend to have access to different technologies and knowledge, hence the use of 3D culture, stem cells, and primary tissue in one, but polymers, microfluidics, and 3D printing in the other.
This last point is changing all the time. Every couple of months there’s another paper calling for developmental biologists and engineers to work more closely together — there’s a lot of exciting research that can be done when biological knowledge meets tissue engineering technology! (And of course, “organoids-on-a-chip” are a thing now.)
From a practical perspective, it remains to be seen what kinds of models will be adopted by industry or accepted by the FDA. It was only last year (2017) that the FDA announced that it would begin evaluating the organs-on-a-chip developed by Emulate:
On April 11, 2017, FDA announced a multi-year research and development agreement with a company called Emulate Inc. to evaluate the company’s “Organs-on-Chips” technology in laboratories at the agency’s Center for Food Safety and Applied Nutrition, one of a number of FDA efforts to help evaluate this chip technology…
Research will begin with a liver-chip but the agreement may expand in the future to cover additional organ-chips, including kidney, lung and intestine models. The ultimate goal is to predict how specific organs will respond to exposure to potential chemical hazards found in foods, cosmetics and/or dietary supplements with greater precision than other methods currently being used, such as cell-culture or animal-based tests.
Organs-on-chips have been the focus of a public-private collaboration between FDA, the federal Defense Advanced Research Projects Agency (DARPA) and the National Institutes of Health (NIH) since 2012.
Organoids and organs-on-a-chip, organotypic cultures and microphysiological systems — whatever you decide to call them, methods for increasing the relevance and utility of in vitro tissue models will be here to stay.
Shortly after I wrote this answer, the same folks who produced the Caco2 intestine-on-a-chip model published Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids, beautifully demonstrating the interaction between organoids and organ-on-a-chip. Here are their organoids-on-a-chip:
Nice blobby villi here. The addition of intestine-specific blood vessel cells also improved cell monolayer and villus formation.
And if you look at gene expression data, Caco2 systems cluster by themselves, while the organoid chip very closely resembles native duodenum.
This article was originally posted on Quora and written by Jennifer Hu
