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Engineers grow pancreatic organoids that mimic the real thing (news.mit.edu)
204 points by geox on Sept 13, 2021 | hide | past | favorite | 21 comments



While the pancreas is of particular interest to me, its presence in the title is the worst sort of clickbait: it buried the lede.

The real invention is a batch-reproducible gel in which all sorts of tissue can be grown. That’s really exciting!


We've tried the organoid approach, but ultimately, you need an animal model to properly model blood flow, immune response, etc. So we developed a pig model of pancreatic cancer: https://journals.plos.org/plosone/article?id=10.1371/journal...

My lab uses an engineering approach to develop new minimally invasive cancer therapies, and some of the new therapies are already being translated into early phase human trials: http://www.edboas.com/lab/

We're hiring biomedical engineers, so please contact me if you're interested.


I'm pretty sure you are well compensated and all that (though probably not as well as your bosses), but also just personally, thank you to you and everyone in your lab.

Cancer killed my grandfather, my best friend, my aunt, and so many other people I know, and what you are working on isn't just making money, it's saving lives.


Are there any plans to study and treat neuroendocrine tumors?


hello,

first thanks for your work, since you're in advanced medical territories, what other labs / people / work do you follow with interest ?


that sounds incredibly interesting actually, great work


You mean you purposefully grew tumors on pigs?


Yes, we induce pancreatic cancer in pigs, and then we try to treat the cancer.

One important question is why so many new cancer treatments are successful in mice and rats, but then fail in human trials. You could point to genetic differences between mice and humans, but I think another important factor is simply the size difference. Just like a scale model of an airplane won't fly the same way, there are also scaling laws in animals. Large animals have a lower metabolic rate (per kg), require lower drug dosing (mg/kg), have more defense mechanisms against cancer, and have differences in blood flow and many other variables. We suspect that cancer treatments that work in pigs will be more likely to also work in humans.


The size of the tumor likely makes a big difference too: a centimeter-sized lump contains 1000x more cells than a millimeter-sized one. It will contain 1000x more drug-resistant cells (given identical mutation rates). For example, a human brain tumor is likely to already contain hundreds of cells carrying a mutation for every amino acid in every protein. Thus for any inhibitor drug you try, hundreds of cells will already be resistant, and they will grow back the tumor in just a few months. That’s much less likely to be the case in a mouse tumor.


You could also say that induced cancers are somehow different from naturally occurring cancers so treatments targeted toward 'artificial' cancers fail to work on real things.


Could be what GP says, could be what you say, but the only way to know for sure is to try and reduce the differences.


I wonder if this will have application for diabetics.


I know someone that has been effectively cured from type 1 diabetes from islet-cell transplantation into the liver by injection into arteries in the liver.

This seems to be one step closer to being able to that without the problem of harvesting those islet cells from living human pancreases.

However, the main problem remains, if you are not already on immune-suppression you will have another autoimmune-reaction to your insulin producing cells. I don't know the status of highly specific immune-suppression like that but I know as a type 1 diabetic that I rather keep my diabetes if required to have a functioning immune-system.


I found this study where gene therapy was used to alter alpha cells to behave more like beta cells quite interesting:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757249/

I don't know if much has happened with the research since, but the theory was since only beta cells are targeted by the autoimmune response, perhaps these "pseudo Beta cells" might be left to produce insulin without being attacked. Does mean you're potentially left with inhibited glucagon production though. Perhaps gene therapy altered alpha cells could be implanted rather than altering the ones you have.


> highly specific immune-suppression

It is being developed and has cured type 1 diabetes in two clinical trials:

1. "Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes" https://doi.org/10.1126/scitranslmed.aaf7779

2. "Safety and feasibility of intradermal injection with tolerogenic dendritic cells pulsed with proinsulin peptide—for type 1 diabetes" https://doi.org/10.1016/S2213-8587(20)30104-2

A press release about the study: https://www.cityofhope.org/breakthroughs/safety-trial-for-ty...

They are currently recruiting for the next clinical trial. Perhaps you could participate?

"An Immunotherapy Vaccine (PIpepTolDC) for the Treatment of Patients With Type 1 Diabetes" https://clinicaltrials.gov/ct2/show/NCT04590872


Unfortunately, you really can't (except as an absolute last resort) suppress the immune system of children. Seems as most Type 1 diabetics are diagnosed in early childhood and the age of onset/diagnosis is creeping forward, an approach involving immunosuppressants is not likely feasible for the majority. By the time you're old enough to take immunosuppressants the beta cells are well and truly destroyed and they don't regenerate.


The new treatment isn't an immuno-suppressant. It de-programs the immune system so it stops attacking the beta cells. It's essentially a highly-effective allergy shot.


Thanks for the clarification. Your links aren't working now (site maintenance).

However, I did view them initially. The study abstracts mentioned immunotherapy, I didn't even realise we were capable of "de-programming", or that that was a considered immunotherapy!

My 3 year old daughter is the Type 1 diabetic in our family. However, I'm immunosuppressed due to a (seemingly) entirely unrelated autoimmune disease, Sarcoidosis. I'll definitely be keeping an eye out for this more targeted approach to immunotherapy.

If you happen to have links to any other papers/articles using similar techniques (even for different diseases) then I'd be quite curious to read up on the topic. Thanks!


That's all I have at the moment.


Could be maybe also of use for alcohol use disorders where the pancreatic cells are chronically damaged from the metabolites of ethanol.


Finally, my garloid can have a friend




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