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Human body-on-chip platform could speed up drug testing

europeanscientist.com

11–20 of 47 posts

Re: Human body-on-chip platform could speed up drug testing

#11

Earlier quoted context omitted.

OK why the need for a physical chip, why not replicate in software?

Because we can't effectively model the behavior of human tissue in software.

by a long shot, too.

Re: Human body-on-chip platform could speed up drug testing

#12
post #5

Earlier quoted context omitted.

This isn't a chip for implanting inside the body; this is a microfluidic chip that replicates some body systems in the laboratory.

OK why the need for a physical chip, why not replicate in software?

Look at how much energy and computer cycles they have to put into just for folding a single protein and then realise that scaling it up at our current level is basically impossible: https://foldingathome.org/

Re: Human body-on-chip platform could speed up drug testing

#13

Earlier quoted context omitted.

OK why the need for a physical chip, why not replicate in software?

Because we can't effectively model the behavior of human tissue in software.

We can't even effectively model basic chemistry. We can't a priori tell you what color a chemical will be, much less many of its other properties.

Re: Human body-on-chip platform could speed up drug testing

#14

If you can really, truly get liver-on-a-chip to work, it's going to positively change drug testing forever and will be the first huge win for tissue engineering. You can throw away animal models for tox screens forever, and that's great news. It will save vast amount of time and money. By using a much better proxy model for humans (slices aren't organs, they have different rheological characteristics and morphology,…

Meh. There are plenty of human cell line derived assays for things like membrane permeability, liver toxicity, etc.

Those assays are super helpful, but don't replicate what happens in humans. They are good boxes to check, and can help weed out compounds early, but just because a compound passes the assay doesn't guarantee something weird won't pop up in humans.

Re: Human body-on-chip platform could speed up drug testing

#16
post #14

If you can really, truly get liver-on-a-chip to work, it's going to positively change drug testing forever and will be the first huge win for tissue engineering. You can throw away animal models for tox screens forever, and that's great news. It will save vast amount of time and money. By using a much better proxy model for humans (slices aren't organs, they have different rheological characteristics and morphology,…

Meh. There are plenty of human cell line derived assays for things like membrane permeability, liver toxicity, etc. Those assays are super helpful, but don't replicate what happens in humans. They are good boxes to check, and can help weed out compounds early, but just because a compound passes the assay doesn't guarantee something weird won't pop up in humans.

Is it possible that these proxies you mention could weed out compounds incorrectly? For example, if we have a liver proxy that fails on drug A, is it possible that drug A will work fine in the human body provided that there’s a lot of other processes that could contribute to the liver?

Re: Human body-on-chip platform could speed up drug testing

#18
post #7
post #6

Does anyone have a layman-accessible explanation for how exactly this works? My last biology class was freshman year of college, but I find the "body-on-chip" startups incredibly interesting. I take it this is different than "growing" organs via stem cells?

Basically, when you are growing organs or organoids (or 3d printing organs) with stem cells (which are used for organ on a chip too), you're actually trying to recreate the physical organ itself in it's original structure/function. You can imagine in the extreme the end result of trying to do this with a lung would be actually having a working lung that you could transplant into a person. Organ on a chip is less abou…

This reminds me very much of manufacturing quality testing, where you do initial DoE and validation builds to develop knowledge of the process. Eventually the knowledge of procc behavior at boundary conditions is known well enough that you can start to use alternative process monitoring approaches, like building a representative mockup of in-vitro conditions that represents the actual use conditions.

It doesnt have to be the same vector, just the same eigenvector.

Re: Human body-on-chip platform could speed up drug testing

#19
post #5

Earlier quoted context omitted.

This isn't a chip for implanting inside the body; this is a microfluidic chip that replicates some body systems in the laboratory.

OK why the need for a physical chip, why not replicate in software?

It's not a chip like a CPU. It's chemistry and biology.

Re: Human body-on-chip platform could speed up drug testing

#20
post #16
post #14

Earlier quoted context omitted.

Meh. There are plenty of human cell line derived assays for things like membrane permeability, liver toxicity, etc. Those assays are super helpful, but don't replicate what happens in humans. They are good boxes to check, and can help weed out compounds early, but just because a compound passes the assay doesn't guarantee something weird won't pop up in humans.

Is it possible that these proxies you mention could weed out compounds incorrectly? For example, if we have a liver proxy that fails on drug A, is it possible that drug A will work fine in the human body provided that there’s a lot of other processes that could contribute to the liver?

Absolutely. That's the flip side of in vitro and animal testing. You might see a negative signal and stop development, only to find out that it can't be replicated in humans.

The cell line assays replicate much of what happens in humans, but not all of it, in particular the interactions between different tissues. For example, a drug might be toxic in a liver assay because a reactive metabolite damages the cells. But in an actual human, you might never see those high of concentrations in the liver or there may be a process (like glutathione adducts) that deactivates the metabolite and prevents cell damage.

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