Jun 15 2010

Growing New Livers

A team as Mass General has published the results of their preliminary research into growing new livers from hepatocyte stem cells. The work is encouraging – but to put it into perspective, it is still a long way away from growing fully functional transplantable organs.

What the team did was take rat livers and wash away all of the liver cells leaving behind just the connective tissue. They used this connective tissue as a scaffold on which to grow a new liver with hepatocytes. They then transplanted the new liver into rats. They report that the artificial livers survived for a few hours.

This is obviously a long way away from an artificial liver. First, the new livers had only hepatocytes, but not the other kinds of cells that make up a normal liver. So even if this technique worked completely, it would only create a partially functioning liver.

Another obstacle to overcome is creating a liver that has something approaching a normal infrastructure, including blood vessels and bile ducts. It’s not enough to have a mass of cells, they have to have the proper structure to function. This is not a trivial obstacle.

In fact the liver may be a deceptively difficult organ to grow in this manner. Other teams have had success using essentially the same technique with hearts – using a scaffold on which to grow new heart cells. Heart cells have the advantage of synchronizing themselves as they grow, so they beat together. The challenge is growing the internal electrical system of the heart, but this can be bypassed by using a pacemaker.

Other organs will be of varying complexity. A pancreas doesn’t seem as difficult as a lung or liver, while kidneys have a complex internal structure.

The questions is – how much potential is there in the scaffolding approach to growing organs? This seems like a stop-gap measure – a partial solution to the problem of how to grow organs. It may be useful for a couple of different kinds of organs, likes hearts, and for some other body parts – a trachea was transplanted using this method. But it seems unlikely, without further major breakthroughs, that this approach will be the ultimate solution to growing organs.

Growing new organs from scratch – from an embryonic state – may be the only way to get the full infrastructure and cellular organization. The problem here is that it takes time. An adult organ may take a decade to grow. For some organs an adult organ, or close to it, would be necessary – like heart and lungs. For others, even a several year old organ may suffice. A small liver or kidney would still provide significant function, and may continue to grow as the recipient ages.

There is also the  question of what to grow the new organs in. Ideally we would grow them in vats – some completely artificial environment. But this will likely be a huge technological hurdle. There are insurmountable ethical problems to growing them in people – clones that would serve as organ banks (like in the movie, The Island). It is interesting to consider the public reaction to other human options, such as growing them in headless torsos – just a formless mass of cloned human tissue full of organs being fed intravenously.

There is also the option of genetically engineering animals to grow cloned human organs, and then sacrificing them when the organs are needed. Perhaps they can be engineered to be immunologically naked, and then matched to the recipient when it comes time to harvest the organ.

There are two significant advantages to growing organs. The first is that we have a shortage of donated organs – people die waiting for organs to be transplanted. The second is the issue of tissue rejection. Getting a transplant even from a compatible donor requires a lifetime of immunosuppressant drugs and the risk of rejection. A transplant of  your own cloned tissue, however, would be 100% compatible and therefore not require drugs or risk rejection. This is a huge advantage, which would revolutionize organ transplants.

Conclusion

This latest study is a baby step forward in one technique which is likely to be very useful, but ultimately limited, in terms of a final solution for organ transplants. But it’s a step. We need another 50 baby steps or so before we reach our goal, but there are useful milestone along the way. I think we will see in the next decade grown hearts for transplant, and maybe even grown livers and pancreases. Skin is another organ that will likely occur sooner than later. But such predictions are inherently unreliable – there remains major obstacles to overcome and they cannot be predicted in the short term.

12 responses so far

12 Responses to “Growing New Livers”

  1. eeanon 15 Jun 2010 at 9:27 am

    I thought they could grow skin in a lab already.

  2. bluedevilRAon 15 Jun 2010 at 9:48 am

    I can’t wait for JB Handley, Homeopath Benneth or some other loon to get ahold of that cloning quote. “Novella wants to clone headless torsos and harvest them for organs! What a monster!”

    I’m sure it would provide for some quality entertainment.

  3. cdegrooton 15 Jun 2010 at 9:52 am

    Given the little I know about embryonic development and the little more I know about genetics, I wouldn’t be surprised if it turns out to be nigh impossible to grow a, say, liver, without having the rest of the body growing in concert. But that’s a gut feeling – I’d love to have my personal spare parts bank, I just fear it’s a long time away (longer, in fact, than repairing damaged organs using nano-scale technology).

  4. locutusbrgon 15 Jun 2010 at 11:05 am

    Another issue with this type of research is that animal model studies do not always translate well to human success. Rats are a very hardy organism and promising research often does not translate into a 1 to 1 results in human studies. Sometimes the rat itself appears to be the reason for the success.
    Still it is an exciting incremental step.

  5. SARAon 15 Jun 2010 at 12:29 pm

    I’m not a doc/scientist – but couldn’t the person who needs the organ be the person who grows the organ.
    In other words, you stick the seeds of the organ (for lack of technical language) into the person who needs them and they incubate their own organs. Perhaps it would help with the rejection issues as well.

    Of course the time issue sounds like huge hurdle.

    I know its just another thoroughly uniformed idea, but it seems like a good idea in my head.

  6. Steven Novellaon 15 Jun 2010 at 12:34 pm

    Sara – that is not a bad idea, depending on the organ. That would have its own technical hurdles – monitoring it and keeping it functional and growing. Most organs would then need to be translocated to a functional locations, so surgery would still be necessary. For a large organ there would also be the question of room – you have to grow the new organ before you can take out the old one, which may be partially functioning.

    But this may become an option.

  7. komouseon 15 Jun 2010 at 2:30 pm

    Markus Grompe’s lab has already been growing human livers inside of mice. This article talks about the use of this technology for drug testing, but he is also trying to set the system up in larger animals for organ transplantation. Ideally you would use the patients own cells to repopulate the animal liver, thus avoiding the need for immunosuppressant drugs.

    http://www.healthcaretechnologyonline.com/article.mvc/OHSU-Turns-Mouse-Into-Factory-For-Human-Liver-0001

  8. superdaveon 15 Jun 2010 at 2:57 pm

    I know one of the co authors. However I have no more useful information than this.

  9. superdaveon 15 Jun 2010 at 3:00 pm

    Actually I can. The way he always sells this research is with the claim that people who have liver failure but are otherwise healthy could use a device such as this to assist liver function during a recovery period, after which their original liver takes over.

  10. CivilUnreston 15 Jun 2010 at 4:13 pm

    I have a subscription to The Economist and, recently, their Science and Technology section had an article about using 3D printers to craft organs. The article itself requires a subscription, but an NYTimes blogger referenced it:

    http://freakonomics.blogs.nytimes.com/2010/03/02/an-organ-printer/

    Of course, the company’s claims are likely overstated and many years away from usefulness. Still, I imagine it’s possible to use such technology to lay down a very complex scaffolding (with various growth factors embedded) and/or stem-like cells from different tissue types.

    PS: I know it sounds creepy, but, other than a visceral disgust, what’s wrong with engineering a clone of myself to be born with severe anencephaly? Do religious folks believe that even things without brains have souls?

  11. daedalus2uon 17 Jun 2010 at 10:41 am

    This is very interesting research and growing organs is a very difficult challenge and I think Dr Novella is correct that one of the main difficulties is the internal microscopic structure. No organ is composed of only one type of cell. There are multiple cell types that perform multiple functions and they all have to work together “in sync”. The only reason they do work together “in sync” is because there are control systems that regulate them to work together in sync. These control systems are not understood, and are likely the reason the organ failed in the first place.

    That control system functions best when the liver is functioning best (that is why there is good liver function, the control system is acting to cause the liver to function well and a well functioning liver has a control system in good shape that is working effectively).

    There are systemic health effects that have impacts on liver health. When people get liver transplants, it is not atypical for the liver to fail much faster in the recipient than the liver would have failed had the donor lived. I suspect this derives from the physiology of the recipient calling on the new liver to do things that cause that liver to fail.

    I think this is the generic problem of transplanted organs, and will be the major problem with using stem cells. Organs fail for a reason (even if we don’t know what that reason is), and if that reason is not corrected, it is unreasonable to expect a new organ to not fail also.

    I have only seen the abstract, but I suspect that they put their whole liver graft in the rat without taking out any of the rat’s healthy liver. The liver control system must have pathways that limit liver size, and that even reduce liver size when there is more than enough. Physiology is not going to try and support an extra liver with crappy performance (the initial state of the transplanted liver) when it has all the healthy liver it needs. Better to ablate the liver cells with marginal functionality.

    Taking out part of the healthy liver might stimulate the liver control system to produce liver growth factors that might accelerate the growth and healthy activation of the new liver.

  12. BillyJoe7on 17 Jun 2010 at 5:41 pm

    Daedalus,

    How much of what you say above is speculation like the control mechanisms getting rid of deficient cells if it has enough efficient cells; and that controls limit liver size; and that liver failure is often the result of poorly functioning control systems?

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