Views of the Cost and Time Required to Build an Organ Engineering Industry

Below find linked an open access paper that looks at what has to be done to reach the goal of engineered patient-matched organs, built as needed for transplantation, and the resulting end to shortages and waiting lists. It is interesting for putting some figures on the table for time and cost for the various lines of development required. From my perspective, over the longer term of the next twenty to fifty years, the interesting race in tissue engineering and regenerative medicine is between as-needed production of patient-matched tissues and organs for transplant on the one hand and in-situ restoration of all damage in existing tissues and organs on the other. If organs can be comprehensively repaired in place through regenerative medicine, a process that would have to incorporate the SENS portfolio of damage repair therapies for the old, and thus be much more than just an evolution of the stem cell approaches in their infancy today, then there would be little need for transplantation. At present the production of tissues for transplant is much more advanced, however, on the verge of producing useful, functioning sections of internal organs for medicine rather than research.

Thus, over the next couple of decades the immediate race is between the varied established approaches to engineering organs to order, between the range of possible ways to improve transplantation procedures, and between the research groups specializing in different organs or methodologies. These methodologies include decellularization of existing donor organs, xenotransplantation of transgenic pig organs, the bioprinting of tissue scaffolds and cells, and force-growing tissues from stem cells, with the latter still having a long way to go yet. Researchers have demonstrated tiny sections of functional tissue for the kidney, liver, intestines, thymus, and various other organs, but at present these are intended to speed up research. They are only a stepping stone. Scaling up beyond a sliver of tissue is a real challenge, as it involves building complex vascular networks to supply the cells, something that has been a roadblock for more than a decade now, and this despite a great deal of funding, ingenuity, and effort. This is why decellularization and xenotransplantation (or both together) have gathered support and funding: they represent a shorter path to expanding the supply of viable organs.

There are other challenges to the near future of organ engineering beyond those involved in building blood vessel networks of tiny capillaries. All will require time and effort to overcome, and while the scientific community devoted to this work has better funding and support than those involved in aging or rejuvenation research, there is never enough funding or support as would be justified given the end results. No society in history has devoted as much to research as would make sense from a purely logical point of view, sad to say. It is human nature to be consumed by what is, and not with what might be. Progress is an afterthought, which is why even in fields with a sizable output of papers and trials, it is still the case that we need the advocacy of groups like the Methuselah Foundation and the New Organ prize series. Research prizes and contests such as the NASA Vascular Tissue Challenge spur progress, and faster progress towards engineered organs is a good thing indeed.

Bioengineering Priorities on a Path to Ending Organ Shortage

There are four main pathways that we will consider at a high level on a path to end organ shortage through bioengineering: (1) bioprinting organs and tissues, (2) recellularization strategies, (3) cellular repair or regeneration, and (4) xenotransplantation.

Bioprinting

3D printing, or layer-by-layer building of organs and tissues, is a process in which cells and intercellular materials are laid out (also referred to as 3D bioprinting, biofabrication, or additive manufacturing) to create a functioning tissue or organ. This living construct would then be implanted into the patient to replace lost organ functionality.

Recellularization Strategies

Through the use of existing tissue scaffolds from other organs or biologic material, new functionality can be provided to patients. These scaffolds must first be cleared of all endogenous cells, and then repopulated with new cells to form a functional bioengineered organ, at which time the newly formed organ would be implanted into the patient. Cells can also be seeded onto/within biodegradable scaffolds that slowly breakdown after implant, leaving only the desired cells and the extracellular matrix they have deposited. One example of promising work in this area is tissue-engineered autologous urethras for patients.

Cellular Repair or Regeneration

In vivo repair/regeneration of damaged organs can be accomplished by delivering small molecules, growth factors, or genetically modified cells into existing organs in a patient. It is expected that the new cells integrating into existing tissues may increase tissue functionality through a paracrine effect, as well as by directly supplementing functional cells. Additionally, growth factors or genome-editing techniques could boost organ functionality or stimulate regeneration. Genome-editing techniques, such as the clustered, regularly interspaced, short palindromic repeat (CRISPR) technology, are showing promise in this area. It is expected that advances in CRISPR and other genetic modification systems could repair tissues that harbor genetic damage as a result of cancer, disease, or trauma, and thereby remove the need for replacement tissues in some patients.

Xenotransplantation

The use of genome-editing of animals to alter immune recognition and prevent organ rejection is another promising area that could help reduce the increasing shortage of donor organs. In principle, suitably modified animal organs could then be transplanted into human patients (xenotransplantation). Much uncertainty remains regarding the appropriate functional and genetic modifications and the necessary safety precautions that would be required for successful xenotransplantation, but some encouraging progress is being made.

Technical Feasibility and Cost to Arrive at Successful Solutions to Bioengineering Challenges and Limitations

We reached out to 35 leaders in the field to delve into each of these challenges and limitations to provide perspectives on the technical feasibility of addressing each of these bioengineering challenges, as well as the estimated cost to arrive at successful solutions for the proposed bioengineering challenges. The majority of those polled (67%) indicated that we have, for the most part, identified the major bioengineering challenges. These cover a wide range of areas, including manufacturing, storage and distribution challenges, regulatory and standards challenges, and technological challenges.

Mapping: 5-10 years, costing $1M-50M

It is important to improve our understanding of the detailed structures and organization of cells within each organ to accurately bioengineer tissues to replace lost functionality. Maps of cell placement, phenotype, function, organization, and interaction have not been created in sufficient detail to reliably provide a blue print to repair or replace the functions of existing organs. The generation of a comprehensive "cellular atlas" for each organ would provide great benefit to reconstruction and repair of organ functionality. This cellular atlas would consist of both genetic and development mapping. In many solution pathways, bioengineered organs will likely not be perfect mimics of native organs, but nonetheless will deliver the functions needed. For example, pancreatic islet transplants delivered into the liver can function, but do not replicate the microenvironmental pancreas map.

Vascularization: 5-15 years, costing $50M-100M

Engineering thick tissues in vivo or ex vivo requires the ability to create an internal vascular system that provides the required nutrients to all cells. This has not yet been achieved for tissues thicker than a few millimeters. In order to engineer thick-tissue organs such as the heart, liver, lung, or kidney, this challenge must be overcome. Some progress has been made toward this goal. For example, co-transplantation of hematopoietic and mesenchymal stem/progenitor cells has been shown to improve vascularization in a bioengineered tissue graft model. Developing strategies such as this to improve vascularization in bioengineered tissues and organs, through the addition of cells, small molecules, biomaterials, or other methods, will aid regenerative mechanisms as well as ensure sufficient diffusion of nutrients and oxygen and removal of waste.

Integration: 5-15 years, costing $100M-1B

The nervous and lymphatic systems are not intentionally reestablished at the time of organ transplant, so it remains unclear if bioengineered tissues and organs will behave in the same manner as their native counterparts, or if they will require additional connections to successfully integrate with the patient's body. A need for innervation and lymphatic drainage may be a complex challenge that varies from one organ to the next. Solutions may also vary with the pathways being pursued. Connecting thick tissues to an existing host's vasculature will require different techniques than integrating new vascularized tissues, or other thin-walled structures. Interesting work has shown nerve regeneration within a biosynthetic extracellular matrix for corneal transplantation. Expanding work such as this to larger tissues, and eventually to bioengineered organs, will be critical to ensure proper organ function.

Immunosuppression: 5-10 years, costing $1M-50M

Immunosuppression has been critical for allowing for graft survival and limiting rejection after organ transplantation. However, the long-term use of immunosuppression carries with it several side-effects, such as progressive renal impairment. When cells or tissues are implanted into new patients, immunosuppression requirements can greatly reduce the quality of life, damage the transplanted organ if left unchecked, and increase the risk of infection, cancer, cardiovascular disease, diabetes mellitus, and others. Immunosuppressive drugs are also expensive. Eliminating the need for immunosuppression would be ideal. This may be addressed by using autologous cell sources, the genetic modification of cells and tissues, and possibly by methods we have not yet conceived to induce tolerance in organ transplantation.

Cell manufacturing and sourcing: 5-10 years, costing $50M-100M

There is great need to create more reliable sources of different types of cells that are required to produce each desired organ function. We do not yet have enough reliable, replicable sources of key cell types that can be provided at economical costs and scale. The purity and quality of existing cell sources must also be improved to better prepare bioengineered tissues and organs. Autologous cell sourcing techniques are preferred to banking of allogeneic sources, as the use of autologous cells would mitigate rejection and minimize the need for immunosuppression requirements; however, allogeneic sources are far more cost-effective.

Envisioned Impact Eliminating Organ Shortage Would Have on Disease and Global Economies

An extensive report on improving organ donation and transplantation was prepared by the RAND Corporation in 2008. This report is comprehensive and interested readers are encouraged to review. The authors provided projections on organ donation and transplantation rates, quality-adjusted life years and life years saved, health risks to patients, living organ donation, cross-border exchange, and health inequalities. Their most favorable scenario projected health benefits including transplanting up to 21,000 more organs annually in the EU, which would save 230,000 life years or gain 219,000 quality-adjusted life years (QALYs). For social impacts, it was predicted that increasing organ transplantation will have a positive effect on quality of life for organ recipients, and will lead to increased participation in both social and working life activities. RAND Europe projects the economic benefits of implementing policies to improve organ donation and transplantation of up to €1.2 billion in potential savings in treatment costs, and productivity gains of up to €5 billion. These calculations are based solely on increasing transplants by 21,000 more organs annually. Imagine the projected savings globally for completely eliminating organ shortage!

Comments

I thought I read somewhere in 2015 that one of the big ivy league schools had gotten close to being able to "vascularize" tissue up to an inch in size.

Thinking outside of the box, I'm not sure that for some organs that organoids of an inch in size might not be enough. In other words, you could conceivably grow multiple kidney or liver or pancreas (etc) organoids and attach them to the blood supply and they should in theory be able to do the job of a larger organ.
It's the heart, lungs and digestive system that are problematic but the "support" organs should be solvable within the next couple of years to five years.

Bearing in mind this is a wild ass guess.

Posted by: xd at May 4th, 2016 1:14 AM

Bioprinting organs is a long way off. Vascularization is only one issue and it still hasn't been completely solved. It may be possible to bioprint skin in the next 30 years, but things like hearts, livers, lungs, etc. will be impossible for the next 50 years or so. The technical hurdles are vast. I'd love to be proven wrong.

Posted by: MissKaioshin at May 4th, 2016 2:05 AM

@MissKaioshin: I'd love you proved something, for a change.

Posted by: Antonio at May 4th, 2016 4:17 AM

Why would she ever back up any claims when she can just wildly throw dates around to make her seem credible? She never actually has anything to back up her statements, just appeals to authority about what some "scientists" say on the matter.

Posted by: Ham at May 4th, 2016 4:55 AM

Can we just ignore her?

Posted by: Barbara T. at May 4th, 2016 8:34 AM

If we can manufacture organs using these techniques, we can manufacture entire bodies using the same techniques. Combine this with repair of the brain itself (apparently there is a start-up doing this as well) and we can start reanimating people from cryo-suspension once we have the cure for aging.

Perhaps we see all of this in the latter half of this century.

Posted by: Abelard Lindsey at May 4th, 2016 10:13 AM

The nice thing about all of this is that there are large multiple markets for these technologies - synthetic meats, organs and tissues for transplants, all kinds of bio-engineered materials for all kinds of industries. This means this kind of bio-engineering technology being a huge industry with lots of suppliers and customers. By the time we are able to bring people out of cryo-suspension, there is a whole industry of off the shelf capabilities that we can utilize to do such.

Posted by: Abelard Lindsey at May 4th, 2016 10:19 AM

No need for antiaging if you can print whole body. But Reanima project is not about "defreezing". It probably can't deal with ischemic damage and ice crystal formation. Defreezing process itself is also unclear at the moment. I'm afraid that frozen tissue will melt into a mush when you try to just heat it up.

Posted by: Martin S. at May 4th, 2016 1:52 PM

Well in the last few weeks we already have "breakthrough" multi-layer artificial skin with sweat glands, hairs etc. I suspect growing viable skin in the lab is closer by orders of magnitude than 50 years away.

Posted by: xd at May 4th, 2016 2:52 PM

Antonio: I can't prove what will happen in the future. It hasn't happened yet. I can't prove that bioprinting entire transplantable organs won't be accomplished for another 50 years. I would LOVE to see it happen much, much sooner, however. But reality doesn't care about what we want.

Ham: Anthony Atala himself has said that bioprinting whole organs is decades, not years, away. As far as I know, he hasn't changed that estimate.

Barbara T.: I'm not trying to upset anyone. Like I said, I would love to be proven wrong. I'm interested in this stuff, too. I'd love to see it advance rapidly. But I'm not very optimistic because of what folks like Dr. Atala have said, along with many others.

xd: I hope you are right, but "breakthroughs" seem like they're a dime a dozen. We hear about advancements in stem cells, CRISPR, tissue engineering, etc. every month. Maybe they're real, or maybe they're hype. But in the meantime, no treatments for aging seem to be in sight. I've actually been following this stuff for about 10 years, and I remember hearing about the 2010s will be the decade where anti-aging and regenerative medicine really take off. But we're over halfway through this decade, and it still hasn't happened yet. Now I'm hearing it's going to be the 2020s or 2030s. I wouldn't be surprised if, in 10 years, it's pushed back again.

Posted by: MissKaioshin at May 4th, 2016 3:39 PM

MissKaioshin unfortunately, you're absolutely right. Bioprinting in the foreseeable future, only suitable for the creation of cartilage, but with a more complex organs failure can be expected like in operations of Macchiarini. We can not print the organs without knowing complex patterns of interaction between the matrix and the cell, between neighboring cells. Tissue formation relies on cell-cell and cell-ECM adhesions via transmembrane proteins to transduce signals between the intra- and extracellular domains that are linked to actomyosin networks and cell-cell/ECM adhesions, respectively. Disruption of cell-ECM adhesions by cell detachment leads to anoikis (a specific type of apoptosis). Similarly, disruption of cell-cell adhesions by inactivation of tight junction causes apoptosis.
There is however hope that it will be possible in the near future to grow human organs in the body of specially selected bred (tolerant to human tissues) animals (which cells can not survive in a human without special medication).

Posted by: Dmitry Dzhagarov at May 4th, 2016 5:45 PM

Dmitry Dzhagarov:

That's about what I figured. I also find it interesting that nobody has bothered to reply since you posted. It makes me think that no one has a good rebuttal...

Posted by: MissKaioshin at May 4th, 2016 11:36 PM

@MissKaioshin: You made a narrow assertion and then used that assertion to make a broad sweeping statement. My rebuttal is this: It does not follow.

Regardless of your inability to argue coherently there are several anti-aging treatments available right now.

Tissue engineering, while in it's infancy is categorically NOT 10-15 years off and repeatedly stating that it doesn't exist in any shape or form is just denying the evidence from several dozens of teams continually posting medical papers with stellar results.

Flatly: you are just plain wrong.

Posted by: xd at May 4th, 2016 11:58 PM

xd:

I think it's worth mentioning that Dmitry Dzhagarov agrees with me. Do you have a rebuttal to what he's said?

The technical hurdles that we still need to overcome in tissue engineering and bioprinting are tremendous. Just because people are working on these problems doesn't mean that they'll actually be solved anytime soon. There have been people working on fusion for decades, to no avail. Back in the 1950s, many scientists thought we'd have human-level A.I. fairly soon. Well, it's been 60 years, and it's still something that lies in the indefinite future. Don't be so sure that the barriers to bioprinted organs will be overcome in the near future. It might take significantly longer.

Posted by: MissKaioshin at May 5th, 2016 12:57 AM

@Misskaioshin,

I am surprised how you love to disagree with any advancement in medical science that Reason may post on this blog. You LOVE to be a naysayer for nearly everything posted. I think you may be right for SOME topics, but given the advances and the resulting synergy in some of these fields over the next 5-20 years, I feel confident we will advance much more that your little brain can comprehend. I.E. The genome with robotics and AI ought to greatly advance our knowledge of ourselves. Gene therapy (CRISPR specifically) has advanced surprising fast over the last couple years and even the continually downsizing of medical robotics systems such as Surgical Intuitive is fascinating to see. Also, stem cells research have also made huge advancement over the last couple years (imagine where we'd be if Bush did not stop stem cell research in the early 2000's).

To assume we will see little medical progress over the next decade or two, IMO, is really naive. I am really surprised, MissKaioshin, you bother to read, let along make comments in this column. And, always very negative, too. The only sticking point I see is the FDA slowing down what is discovered and feasible in the lab to be utilized (legally) on average citizens in the U.S.

Posted by: Robert Church at May 5th, 2016 2:27 AM

"That's about what I figured". No, Misskaioshin, you hadn't "figured" what Dmitry said because you have no scientific knowledge whatsoever (trust me, it is painfully clear from your posts) and you just love saying that whatever advance is being discussed is somewhere between 50 and 100 years away if not downright impossible.

So, since everyone and their cousin here knows that you think that nothing will be accomplished in our lifetime, why don't you just do everyone a favour and stop clogging this blog with the same old trite baseless opinion? You think that we are all going to die. Fine, we got it.

Now go walk the dog or watch a reality show and stop irritating people who are trying to discuss something that is none of your business since you believe it's all baloney.

Posted by: Barbara T. at May 5th, 2016 4:22 AM

Robert & Barbara,

It really makes you wonder why she bothers posting here, huh? I just don't understand the smug tone and self satisfaction about how "that's about what I figured", and when she talks about no one has a good rebuttal to what Dmitry said, like shes getting one over on everyone. She literally does the exact same thing on reddit (a lot), when someone explains to her why she has no clue what she's talking about. It's widely known she has absolutely zero scientific credentials, so all she does is regurgitate what some other people say. Anyone who has a glimmer of optimism is wrong, anyone negative is right. This has all been pointed out before, everywhere.

Posted by: Ham at May 5th, 2016 4:37 AM

To Ham and everyone else:

The problem is that we keep engaging, and whether we try and reason with her (like Robert) or we call her a troll (like me) the result is the same because what she is really after is attention - the more negative the better! The ONLY way to get her off this blog is to ignore her, always and forever until she gets bored. She loves pushing people's buttons and as long as she manages to annoy or upset us she will not stop.

She is not simply "negative", or "a pessimist" but blatantly personality disordered (on the psychopathic spectrum) so let's just deal with her accordingly.

http://www.livescience.com/48128-internet-trolls-sadistic-personalities.html
https://www.psychologytoday.com/blog/your-online-secrets/201409/internet-trolls-are-narcissists-psychopaths-and-sadists

Posted by: Barbara T. at May 5th, 2016 5:56 AM

It is a pity that instead of discussion about the obstacles to achieving the goal - getting young organs for patients - and the most effective ways to overcome them, all the posts were devoted to non-constructive discussions on person of MissKaioshin.
I am interested in the opinion of a group: whether implanting organoids into the body of the embryo of a pig or a goat (tolerant to human tissue) instead of their organ bud, will produce a result - young human organ?
In experiments of Nakauchi H. on creating animals that contain cells or tissues of human origin (animals containing human materials), the possibility of forming human germ cells or brain cells in the body of a pig has often been a focus of bioethical concern. Human organoid instead of strategy of blastocyst complementation with human PSCs, can be a solution to the bioethical problem.
http://www.theriojournal.com/article/S0093-691X(16)30095-4/abstract

Posted by: Dmitry Dzhagarov at May 5th, 2016 10:17 AM

Dmitry you are absolutely right. And that's why we should make a concerted effort to ignore her. The disruption to this blog that you lament is exactly what she is after.

Posted by: Barbara T. at May 5th, 2016 10:28 AM

Barbara T.:

I'm not trying to disrupt anything and I'm not trying to upset anyone on purpose. I am honestly curious to hear about how I'm wrong. If someone who is actually an expert in this domain can explain how and why I'm wrong, I'd be thrilled. Seriously, that'd be great. As I said earlier, Anthony Atala himself said that bioprinting whole organs is "decades, not years" away, but if there are other experts who disagree with him, I want to know. But so far, Dmitry Dzhagarov has agreed with me. I'm not sure if he's a scientist or not, though.

Posted by: MissKaioshin at May 5th, 2016 1:52 PM

You're so full of it. That's exactly what you do. Literally everything you post, everywhere you post is argumentative, dismissive, or you going out of your way to try and be contrarian based on select opinions of select scientists. And I'm not even talking about just this article here, because I honestly have no idea how long it will take nor do I proclaim to know a ton about this area. I mean your posting history is easy to see and it doesn't lie. But even if an expert were to tell you why you were wrong, you would just say he's hyping his own work because he's trying to sell books or get more funding. The only experts that matter to you are the ones who agree with what you believe in, whatever that may be.

I've never seen someone (especially someone that isn't even in the sciences) so confident about so many different things that won't happen and try to pass off their opinion like it's some sort of credible authority. My god, give it a rest.

Posted by: Stem at May 5th, 2016 2:07 PM

Again, I do not understand why such intolerance in people who want to live a long life? Hold in control emotions - they are harmful to your organism. Candidates for centenarians must be impenetrable rationalists! They should never say: "My god, give it a rest." Never!!!
They should smile and say: "Thanks for the info!" (Even if this is nonsense).
By the way in this case, the comments of MissKaioshin were quite logically justified.

Posted by: Dmitry Dzhagarov at May 5th, 2016 2:53 PM

Dmitry, MissKaioshin's comments were not logically justified but at best ACCIDENTALLY justified.

What you read above is her stock answer to anything mildly encouraging that gets posted on this site and anywhere else on the internet. She has no idea whether something - be it organ printing, telomere extension, glucosepane cleaving or whatever - is possible or not. In fact, she has no idea of what these things are in the first place. Just google her name + "troll" and you'll get 254 hits, which is way more than what most legitimate professionals can claim for their name alone.

To give you a measure of her trolling, she claimed in 2015 that self-driving autonomous cars will only be available in the 2030s (to which one commentator suggested she asks Google about "those pesky autonomous cars off the streets of Mountain View because they shouldn't exist". Kudos to you, anonymous commentator), which should be enough for even the most tolerant and well-disposed of people to question if not her motives at the very least her attachment to reality.

To get to the point: if knowledgeable people say that organ printing is not going to happen for another 50 years and provide scientific evidence to back their claim, as you do, the community here will be very happy to take that opinion on board or perhaps try and rebut it with similarly knowledgeable arguments.

On the other hand, if someone regurgitates the same un-knowledgeable and defeatist statements just to get a reaction, which is what she does, then we should think about closing ranks and make a conscious decision to ignore her once and for all.

As you noted above, it is a shame that instead of debating the obstacles to getting organs to patients we waste time on non-constructive discussions about someone's credentials / motivations / personality etc. BUT THIS IS EXACTLY WHAT SHE WANTS! And whether it would be nice for us to be able to control our emotions 100% of the time, human beings as they currently are (but perhaps Misskaioshin has a timeline for when a brain chip that provides automatic control of annoyance will be available) do get frustrated when brought down in extremely dumb ways by someone who is clearly taking pleasure in the enterprise.

So here's my proposal: 1) We completely, totally, and forever ignore her; OR: 2) We do what Dmitry suggested and say "Thanks for the info!" in response to all of her posts.

Posted by: Barbara T. at May 5th, 2016 4:02 PM

Barbara T.:

Whether or not my comments are accidentally justified doesn't matter; they're either justified or they're not. Dmitry is saying I'm (unfortunately) correct. I wish that weren't the case, but it probably is. No one has offered a good rebuttal. How and why am I wrong about bioprinting? You say that I would just reject anyone that disagrees with me, but that isn't true. If one or more reputable scientists with domain-relevant expertise were to explain how I was wrong, I would take it as good evidence that I am wrong. I can't promise that I would do a complete 180 on my opinions,but I would definitely amend them.

Posted by: MissKaioshin at May 5th, 2016 4:41 PM

@MK "Don't be so sure that the barriers to bioprinted organs will be overcome in the near future. It might take significantly longer."

I'm not saying they will be overcome in the near future. I'm saying they've already been overcome. If you had actually read my post and thought about what I'm saying instead of sounding in your own echo chamber you would have got that.

I'll repeat myself and see if you get it: No full sized multi-cell *human* organs have yet been grown.

We *don't need them* to solve the "replace worn out tissue" problem.

We already have organoids for at least half a dozen major organs and tissue from the rest.

We already have full size *mouse* organs for some of the others.

Now here's my key point for the near future. Let's see if you get it this time:
Clusters of organoids will *work just fine* as replacements for *some* of the full sized organs.

And the vascularization thing is really, really close.

As to your straw man on fusion. It's a crappy analogy. A much better analogy is the human genome project.

Posted by: xd at May 5th, 2016 7:54 PM

@Dimitry: "I am interested in the opinion of a group: whether implanting organoids into the body of the embryo of a pig or a goat (tolerant to human tissue) instead of their organ bud, will produce a result - young human organ?"

I wish you had asked a different questin Dimitry. Regardless, I'll take a stab at answering you. Possibly *partially* yes. I think I have read that some university in Australia has grown breast organoids inside rats and they grew into reasonable facsimiles of breasts. But I'd say it produces a *new* organ rather than a *young* organ. The *young* will depend on the age of the stem cells. I'm not clear yet on whether we have a fully worked out process to de-age stem cells without turning them cancerous. Once we do, then yes, it should be plausible.

I had hoped you asked the following question instead: can clusters of organoids replace full sized organs?

I suspect that for e.g. kidneys, livers, pancreas, thymys, spleen and other glandular type organs the answer is yes. I think that for lungs, digestive system or hearts the answer is no. We will need full size organs for these. But we should in theory be able to at least partially repair lungs, hearts and digestive system with just stem cells.

As to how to make stem cells *young* again. There are several different teams working on different approaches. Something like IBM's watson ought to collate the research efforts of these different approaches and see what combinations look like they work.

Posted by: xd at May 5th, 2016 8:03 PM

@Dimitry:

One more thing. I'm not sure I much like the idea of using mice or rats or pigs or whatever for growing organs and then transplanting into humans. There's a non-zero chance of Xeno-HERVs jumping the species barrier from the non-human DNA. It makes me uneasy. Why not grow new organs inside of volunteers, who could then sell them?

Posted by: xd at May 5th, 2016 8:09 PM

@Dimitry:
Here is a link saying it's already been done for mouse vs rat kidneys.
http://www.iflscience.com/health-and-medicine/lab-grown-kidneys-shown-work-animal-models

Now the naysayers will jump on the "human research is years away" piece as vindication. It patently *is not* vindication.
Today it takes years to test drugs in humans. That doesn't mean it takes years to develop drugs. It can take as little as several weeks. It's the testing that takes time.

At the rate of progress that's going on right now, we will have fully functioning animal models for full scale *animal* organs in less than five years.

If we used human volunteers I'd put my own money on full scale human organs in less than five years after success in animals.

Posted by: xd at May 5th, 2016 8:16 PM

@XD,

Regarding your last comment, I think there may be many ethical issues of growing new organs in volunteers, though it would be interesting if they could explore. The idea does kind of gross me out, though. Also, it reminds me of the movie, The Island.

Posted by: Robert Church at May 5th, 2016 8:22 PM

@RC: Seriously? I see it as being exactly the same as getting a transplant.
And as for ethical issues: as long as they're volunteering to do it and getting paid for it I can't see any problem with it.

Also: are you more grossed out or less or equal by the idea of getting organs grown inside a pig? I personally am *way* the heck more grossed out by the idea of putting something inside me that has grown inside an animal. Another, human (as long as they're healthy) not so much.

Anyhow, on another note: I read the base article in a link and it says that the team have also replicated the same result in a pig. I suspect that is proof of principal that it will likely work if grown in a human volunteer icky or no.

Posted by: xd at May 5th, 2016 9:02 PM

@xd,

Any kind of transplant would make me a little quisy (not sure how to spell that word). But, if it is that or being dead, I can live with that,(pun intended):)

I would rather them able to 3d print organs. I had thought they resolved the vascualar issue several years ago. And, I was thinking within 5-10 years we would have 3-d printer organs. But, maybe not.

It seems that to use pigs, we only need to "clean out" their organs and use our dna so the organs are not rejected and they nearly ready for clinical usage from what I have been reading. To me, it seems like a simplistic but logical step moving forward I suppose.

Hopefully, we can wait for a 3d printed organ, or even better have nanotechnology repair or SENS rejuvenate our organs and bodies. I think the latter would be the best and more effective, though.

Posted by: Robert Church at May 5th, 2016 9:16 PM

@RC: Yes you're talking about decellularized scaffolds. It's not quite there but appears to be really close. Sure: grow pigs, cull them for the bacon. Take their hearts/lungs/intestines etc then decellularize them, then grow human tissue on top in the lab. Sure I'm good with that if it works. They are partway there doing it in the lab.

I'm totally *not* OK with a hybrid human/pig organ with actual pig cells in it. But again we're not quite there.

But again, I'm not queasy with the idea of someone growing an organ for me inside of them and selling it to me for e.g. 10 grand and then getting it as a transplant to replace a worn out organ inside of me. I suspect this will be the next easiest after clusters of organoids.

But sure, if we can get 3D printed organs that would absolutely work too. Not there yet though either.

Considering how far we've come in 10 years the progress of the next 10 is going to be awesome (especially since we have much better big data sifting now with machine learning and AI tools like IBM's watson).

Posted by: xd at May 5th, 2016 11:02 PM

@xd,

It is interestin to note that Ray K. made a comment that the genome has now helped make our human biology digitized. Now, our knowledge of the human biology can be increased in a similar fashion as computer chips. If true (and, makes sense to me) we could in fact advance this knowledge with AI/machine learning (I believe this is what Ray is involved with in Google). I think this is pretty awesome and hope we can warp speed the human biology (genome) all the while having the infomation getting cheaper all the time over the next 5-20 years. BTW, I live not far from Google and had a couple interviews with them in Mountain View, but not in the computer or AI field. Where we will be in a few years, I don't know. But I am quite hopeful we'll discover some incredible things using AI.

Posted by: Robert Church at May 6th, 2016 1:16 AM

@xd,
thanks for the info about clusters of organoids. It seems quite logical. But do not forget that in the body, these organoids are not constant - they will develop and who knows where this will lead.
As for the 3D bioprinting. It should be borne in mind that, unlike natural tissues where all cells orchestrated by millions of molecules of the extracellular matrix glycans; in 3D bioprinting tissues cells do not develop together, but according to the laws of cell cultures. The development of such an organ will lead to its rejection, at best, a year or two after after transplantation.
With regard to pigs already "...over 300,000 heart glutaraldehyde crosslinked porcine aortic valve replacements are performed annually to replace stenotic and regurgitant heart" valves. see http://www.sciencedirect.com/science/article/pii/S0142961215005876

Posted by: Dmitry Dzhagarov at May 6th, 2016 2:03 PM

A few comments here.

First, while MissKaoshin has occasionally seemed somewhat unreasonable in her level of skepticism, most of her comments are well within the range of reasonable skepticism. We are a very small community and are constantly confronted by completely ignorant, knee-jerk incredulity (rather than true skepticism) and/or ideological hostility, and I think it sometimes makes us overly-sensitive. Contrariwise, people who are ideologically on "our side" make far less reasonable comments without challenge here on FA! and in other communities favoring intervention in aging all the time.

If we are to make real progress toward our goals, we need to be able to engage respectfully with reasonable critique from the wider public and from scientists who have not yet been brought on board with our goals and strategies. It's also critical that we avoid the dangers of group-think, and of drinking our own Kool-Aid generally. And, finally, and without intending to insult anyone, we don't want people who are curious to come into our discussions for the first time and see discussion threads that look like a cult that is intolerant of heretics and heathens.

Now, a few things on the science:

Posted by: xd at May 4th, 2016 1:14 AM: Thinking outside of the box, I'm not sure that for some organs that organoids of an inch in size might not be enough. In other words, you could conceivably grow multiple kidney or liver or pancreas (etc) organoids and attach them to the blood supply and they should in theory be able to do the job of a larger organ.
Posted by: xd at May 5th, 2016 7:54 PM: No full sized multi-cell *human* organs have yet been grown.We *don't need them* to solve the "replace worn out tissue" problem.We already have organoids for at least half a dozen major organs and tissue from the rest.We already have full size *mouse* organs for some of the others.

The work on organoids by Eric Lagasse and others is very promising, and your basic strategy here makes a lot of sense if it can be shown to work. Still, that work is still in a much more preliminary state than you seem to believe.

For instance, the kidney organoids that he has grown haven't yet been demonstrated to function in the real-world sense of actually filtering the blood (let alone maintaining blood volume and other critical renal functions), because it has been too difficult in the tiny mouse model to hook them up to the bladder, so the proto-organs form cysts, fill with fluid, accumulate urea crystals, and beagin to display signs of fibrosis or other biological infiltration not long after they initially mature into clearly structured mini-kidneys and begin to show signs of function. He also hasn't shown they can fulfill the hormonal metabolism of a real kidney, though he's shown they do at least produce most renal hormones. His proposed next step is trying this all out in a large animal model, in which the renal organoids would be hooked up to the bladder via engineered ureters to see if they could actually both function as kidneys and survive.

Their thymus organoid work, by contrast, is much closer to a meaningful real-world test, having shown signs of T-cell maturation and the functionality of these cells in mounting a rejection response to a foreign skin graft. However, they've not yet been shown to be capable of supporting a successful primary infection, for example.

Liver organoids seem to be closest to being ready for prime time, having demonstrated the ability to normalize most of the liver functions and producing bile that is apparently transported to the diseased native liver where it is apparently taken up, used for conjugation of bilirubin, and excreted. The researchers don't yet know how to produce the trophic signals that appear to be involved in stimulating the growth of the organoids in this model, but that seems like a much later-stage problem to tackle.

Additionally, the elephant threatening to quash many of these tiny organs is the fact that either the organoids themselves, or cells taken from still-developing organs, are originally harvested from embryonic or newborn mice, a process which will never be translated for clinical use in humans. The liver, happily, was done in mice that are further along (8-12 weeks old, similar to adolescence), but with the exception of the pancreatic islets, none of them have been are derived from the equivalent of adult donors, nor from the recipients themselves.

It's certainly conceivable that growing just the organoids from patient-specific precursor cells in a bioreactor that sufficiently recapitulates the complex cues they receive in the developing embryos could eventually allow us to use them as readily as they were used in the mice — but of course, that gets us back to the same core challenges in basic developmental biology and  tissue engineering we face with many approaches to engineered organs.

Posted by: xd at May 5th, 2016 8:09 PM: [As far as growing the organoids in developing pigs], Xeno-HERVs jumping the species barrier from the non-human DNA. It makes me uneasy. Why not grow new organs inside of volunteers, who could then sell them?

In addition to being ethically contentious, possibly risky to the donor (surgical or fine-needle implantation, occupied and potentially interfered-with lymph nodes, and eventual surgical removal), and likely limiting on supply (particularly once we move from emergency replacement medicine into widespread early-stage rejuvenation biotechnology), it's not totally clear that this would work: the case of both the kidney organoids and the liver, as alluded to above, there was evidence that the absence or injury of the native organ was necessary to create the trophic environment that stimulated the growth or development of organoids in the lymph nodes.

The same may be true for the thymus, since the transplant recipients are athymic mice, though no comparison studies have been done with aging normal mice — and it's not clear from the report how old the athymic mice were, so they may have been newborns themselves, and thus still have a lot better environment for growing the organoids. Simply transplanting cells or organoids into the lymph nodes of intact, adult recruits is, on available evidence, not going to work as well, and may not work at all.

Posted by: xd at May 5th, 2016 7:54 PM: We already have full size *mouse* organs for some of the other [organs].

Full-sized, functional replacement organs that last more than a few weeks and replace a missing organ or very substantially compensate for the dysfunction of one that has been badly injured or subject to the ravages of aging? I can't think of a single case. If you're thinking of the lungs, hearts, livers, and other organs worked up from the decellularized-recellularized organ scaffold paradigm, none of those last more than a few weeks before failing and most don't fully make up the function of the original organ even while they survive. Of what were you thinking?

Posted by: Martin S. at May 4th, 2016 1:52 PM: No need for antiaging if you can print whole body.

There is, at minimum, the problem of the brain, which we certainly don't want to replace wholesale. Maintaining and restoring the brain to youthful functionality requires the use of multiple rejuvenation biotechnologies, and I hold out a lot more hope for that approach to be used across the entire body than to replace everything but the brain and then apply them there alone to preserve identity.

Posted by: Michael at May 9th, 2016 10:25 PM

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