Stepping Towards Bioartificial Immune Systems

There is no necessary reason that an artificial organ has to look like or be structured in the same way as the evolved organ it is intended to replace or augment. There are good reasons to try different approaches, largely cost-effectiveness in research and development at the present time, such as by narrowing down work to replicating specific functions rather than trying to encompass everything that a natural organ accomplishes. Further down the line researchers will be aiming to produce improvements on the capabilities of natural biology, however.

This is all especially true of the immune system: so long as it is possible to produce the desired end result of the correct balance of signals in tissues and competent immune cells roaming the body to defend it from pathogens and malfunctioning cells, then it doesn't really matter what the controlling organs look like or where they are in the body. Since immune function can readily be divided up into discrete but interacting portions, there is considerable leeway for researchers to build and augment a bioartificial immune system piece by piece in the years ahead. This sort of work is promising when considering the importance of age-related declines in immune function in frailty and disease. Any means of safely recreating youthful immune system activity in the old is likely to bring considerable benefits.

Beyond that, why shouldn't we all have immune systems that support twice or ten times as many active immune cells, or which are pre-immunized against every known disease, or have other capabilities far beyond the evolved system we're presently stuck with? These and other options are very plausible for the near future:

Engineers have created a functional, synthetic immune organ that produces antibodies and can be controlled in the lab, completely separate from a living organism. The engineered organ has implications for everything from rapid production of immune therapies to new frontiers in cancer or infectious disease research. The synthetic organ is bio-inspired by secondary immune organs like the lymph node or spleen. It is made from gelatin-based biomaterials reinforced with nanoparticles and seeded with cells, and it mimics the anatomical microenvironment of lymphoid tissue. Like a real organ, the organoid converts B cells - which make antibodies that respond to infectious invaders - into germinal centers, which are clusters of B cells that activate, mature and mutate their antibody genes when the body is under attack. Germinal centers are a sign of infection and are not present in healthy immune organs.

The engineers have demonstrated how they can control this immune response in the organ and tune how quickly the B cells proliferate, get activated and change their antibody types. According to their paper, their 3-D organ outperforms existing 2-D cultures and can produce activated B cells up to 100 times faster. The organ could lead to increased understanding of B cell functions, an area of study that typically relies on animal models to observe how the cells develop and mature. "You can use our system to force the production of immunotherapeutics at much faster rates. In the long run, we anticipate that the ability to drive immune reaction ex vivo at controllable rates grants us the ability to reproduce immunological events with tunable parameters for better mechanistic understanding of B cell development and generation of B cell tumors, as well as screening and translation of new classes of drugs."



This is similar to a conversation I had with Liz Parrish about creating a sythetic organ capable of monitoring and producing the correct youthful signals almost like an artificial chemical factor that would replace the other organs. In other words you would create your own endorine system. Very interesting idea which could even use cells modified by gene therapy to produce whatever mix of factors you wanted. Certainly not immediate future technology but I can see it being possible.

SENS were or are developing a cell scrubber for T-Cells if I recall correctly, I could see something like that being incorporated into the body as an augmentation to improve the immune system.

You could also target FOXN1 which has shown to reverse Thymus Involution in mice restoring production of T-Cells and boosting the immune system. They have also replicated this mechanism using Human hematopoietic precursor cells using FOXN1 in-vitro where they were able to rejuvenate and produce mature T-Cells. Not only suggesting that the skin serves a function in the immune system but also proof of concept that FOXN1 if applied to the Thymus would likely see similar results as seen in rodents.

"Beyond that, why shouldn't we all have immune systems that support twice or ten times as many active immune cells, or which are pre-immunized against every known disease, or have other capabilities far beyond the evolved system we're presently stuck with? These and other options are very plausible for the near future:"

Funny you should say that I was reading about scientists growing a second thymus in a rat so this idea is quite plausible. They took fibroblasts and converted them then returned them to the mouse and they functioned. I would say this would be a very good idea and falls into what I would call biological redundancy or in other words over engineering something so it can tolerate a far greater level of stress. Adding an extra Thymus, thyroid or spleen would build in a greater level of immune function as you suggest, quite plausible too given we could do this now with current technology.

Also reason you might find it interesting that we have extra Thymus like glands:

In general I agree fully with your assertion that we could and probably should replace our own organs for far more robust synthetic ones with much more headroom built into them.

Posted by: Steve H at June 11th, 2015 6:56 AM

Also note the ultra conservative approach they take here saying it could help produce therapeutics, help with B cell knowledge and speed up drug testing. I would say that is very unambitious considering such custom organs could potentially replace the organs we have and build into them a lot more redundancy to boot. Very interesting project lets hope they get far more ambitious with it or someone else does.

Posted by: Steve H at June 11th, 2015 10:32 AM
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