Stem Cells That Will Not Be Rejected Will Bring Mass Produced Stem Cell Treatments

CRISPR-Cas9 gene-editing system has made pluripotent stem cells that are functionally “invisible” to the immune system which will prevent rejection of stem cell transplants. Universal stem cells can be produced that will work for everyone and there will not be the need for personalized stem cells. This will bring mass production of stem cells for regenerative medicine.

The immune system is unforgiving. It’s programmed to eradicate anything it perceives as alien, which protects the body against infectious agents and other invaders that could wreak havoc if given free rein. But this also means that transplanted organs, tissues or cells are seen as a potentially dangerous foreign incursion, which invariably provokes a vigorous immune response leading to transplant rejection.

Drugs are currently used to suppress the immune system, but this makes the patient vulnerable to other diseases and problems.

In the new work, three genes were altered. The stem cells were able to avoid rejection after being transplanted into histocompatibility-mismatched recipients with fully functional immune systems.

Nature Biotechnology – Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients


Autologous induced pluripotent stem cells (iPSCs) constitute an unlimited cell source for patient-specific cell-based organ repair strategies. However, their generation and subsequent differentiation into specific cells or tissues entail cell line-specific manufacturing challenges and form a lengthy process that precludes acute treatment modalities. These shortcomings could be overcome by using prefabricated allogeneic cell or tissue products, but the vigorous immune response against histo-incompatible cells has prevented the successful implementation of this approach. Here we show that both mouse and human iPSCs lose their immunogenicity when major histocompatibility complex (MHC) class I and II genes are inactivated and CD47 is over-expressed. These hypoimmunogenic iPSCs retain their pluripotent stem cell potential and differentiation capacity. Endothelial cells, smooth muscle cells, and cardiomyocytes derived from hypoimmunogenic mouse or human iPSCs reliably evade immune rejection in fully MHC-mismatched allogeneic recipients and survive long-term without the use of immunosuppression. These findings suggest that hypoimmunogenic cell grafts can be engineered for universal transplantation.

SOURCES- UCSF, Nature Biotechnology, Tobias Deuse

Written By Brian Wang,

26 thoughts on “Stem Cells That Will Not Be Rejected Will Bring Mass Produced Stem Cell Treatments”

  1. That’s an interesting concept I hadn’t thought of. Use them as temps and scaffolding. You could even limit their telomeres (and knock out telomerase) to limit their division and cancer potential, while also doubling up on suicide genes to prevent them from becoming senescent. I’m not sure that an older adult has enough autologous stem cell capacity to keep up, but if not, we could work on it.

  2. Yes at present these cells would be more vulnerable to cancer or viral or intra bacterial infection. However the final product could easily have suicide genes under the control of something like tetracycline added to deal with cancer.

    virus can probably Be swiftly dealt with in the future by improved vacine technology. Methods to encourage cell turnover could probably even replace the Allogenic cells with native autologous cells over a medium timespan. e.g. build a replacement kidney in the short term out of these allogenic iPS cells, then encourage replacement over the next 15 years.

  3. Can’t they start trying to CRISPR cells into matching the MHC I and II of the host already? Even if it’s not “mass producible” it would be an important milestone and safer in the long run. Best to get started with a proof of concept now.

  4. They inactivated two genes. That’s not something a virus can copy.

    That said, these cells with the inactivated MHC genes would be good breeding grounds for viruses, and I suspect they might make deadly cancers.

  5. Yeah well great. Now you have a cell that is immortal and capable of infinite replication that escapes immune surveillance. We usually call that a metastasis. Better be some checks before we put that into someone’s body. As for the need for stem cells, we already have stem cells in situ everywhere we look in the body. The trouble is not the lack of stem cells but the means to control them in situ. No one seems to be making any headway there.

  6. I dont know what the role of CD47 is but
    eliminating MHC I and II is not enstop regection since there are minor histocompatibility antigens that lead to long term rejection. My guess; CD47 overexpression downregulates the minor histocompatibility response.

  7. Great news for those of us on the upper end of middle age. Lets hope the FDA does not kill too many people delaying this technology.

  8. That thought occurred to me although, if it really is a problem, it might not be a factor until that virus extracted DNA finds its way into a bacterial pathogen. I would tend to believe they have already thought of this, and strongly suspect they have an answer, but it would be nice to hear it.

    Even so, this is thrilling, maybe we can all look back at it in a couple hundred years and recall reading this as the moment just before everything changed.

  9. Wow! Even beyond health care and regenerative therapy this launches a whole new “Transhuman” future. They injected human stem cells into mice with no rejection – so it should work the other way around. The possibilities are endless – from things like new rod/cone structures in your eye to allow you to see into infrared/ultraviolet spectrum, chimpanzee muscles for super strength or cosmetic applications like horns or tails should be possible. Probably wont start here in the U.S. for awhile but give this 10 years (and a lot of research and engineering) and I bet we see it happening in Asia (Cat Ears of course – meow). Hey – did the Singularity happen while I blinked?

  10. And what happens to those cells if they get infected with a deadly pathogen e.g. virus that can copy that part of the gene for itself and is no longer recognized by immune system? – Bye Bye host

  11. Guys,
    maybe it’s just me …. but I’m seeing your comments about some silicon, crystals and stuff, but the article above is about Stem Cells That Will Not Be Rejected. Is there something wrong with the comment system?

  12. > There may be other substrates that are currently being used that would work better – e.g., GaN or SiC.

    I think a key point in this research is that the gold is liquid. That lets the growing BN crystals freely rotate and align themselves to produce a single crystal. It’d be darn hard to liquefy GaN or SiC.

    For that matter, this can’t even be done on the target wafer at all, unless it’s not populated yet. The temperature would destroy any structures you’ve already made there.

    (Of note, pure Ga melts at just 30 C, but it would react with the nitrogen to form GaN.)

  13. I don’t think it’s an unsolvable problem. You just need another atomically flat substrate that is more attractive to BN than gold on tungsten. Like maybe a treated silicon wafer, for example…

    Also, did anyone mention just how thick the gold layer gas to be? Tungsten sputtered onto a silicon wafter, coated with atomically thin gold, only where a BN layer is needed. Tada! If you can’t do it beforehand, just etch away the unneeded BN and the underlying gold afterwards, and recycle it.

    Materials cost would probably go up, but it’s the capital costs that kill. A few more cents per chip is nothing.

    For an +entire+ 12-inch wafer, assuming 100% coverage, complete loss of gold, and a ‘thick’ layer of gold
    (150mm^2*pi) * 1 micron * 20g/cc * $40/g = $56.55

    Raw materials cost has nothing to do with it, it’s all about capital costs, throughout, and improved capabilities.

    There may be other substrates that are currently being used that would work better – e.g., GaN or SiC.

  14. Well, as we agree, for certain applications “within reason”, the high cost of the substrate “hardly matters” in the long run. When I think of military leading-edge electronics, I tend to remind myself that $10,000 a chip … for chips of critically magnificent performance, can well be the difference between a system working, or being useless without it. So, yah.  

    It kind of answers the slow-slow-slow problem, too. Who cares? If getting the film onto the substrate takes a whole day, I imagine that a whole oven-load of them could do several dozen a day. And those ovens can be rubber-stamped for higher production rates.  

    More taxing though is “The Transfer Problem”: it isn’t terribly useful unless the boron nitride (hex packed) film can be transferred, essentially without damage, to the “chipmaking and runtime” substrate in some fashion. While I wouldn’t expect BN to stick to the gold underlayment with other than van der Waals forces, let it be know that VDW forces can be pretty darn sticky. 

    However, again remembering other articles, wasn’t graphene discovered and first isolated by way of using sticky-tape on single-crystal graphite sheets, to “peel off” the topmost layer?  Ought to work for BN, too.  

    Who knows.

    Maybe a non-problem.

  15. Considering the low solubility of boron and nitrogen in gold, I’m guessing it can be reused. When you lift off the boron nitride film, most of the gold should stay behind – especially if it has good affinity to the tungsten underneath (if not, replace the tungsten with a more suitable material). You wash/blow/bake the gold traces off of the film, collect it, remelt it, and add it back to the molten gold pool (or make a new one).

  16. The leading performance intel Core i9 sells for $1699 (current google search price).

    I think that the materials cost going into an even more advanced chip is meaningless at this stage, even if they have to throw the gold away (which they won’t).

    Of course the number of chips they can make per hour per $billion worth of fab line is the actual critical factor, and there you have a strong point that this is slow, slow, slow.

    At this stage of development.

  17. New technology will always have to reckon with established technology. The original process for bulk drawing silicon boules was quite expensive and required extensive remelt of the best quartz you could buy. Comparing something that has 80 years of engineering optimization is really not how we should be looking at this.

    Band gap, breakdown voltage and doping properties are what will make or break this particular epitaxy for semiconductors. There are applications where performance justifies the cost…even simple ones like when GaAs is used for Transmitters etc.. There just isn’t silicon in any shape or form that will do the job.

  18. “They grew it on liquid gold films on tungsten substrates”… 

    Compare that to “we melted a bunch of silicon, spun the pot, dipped a cool single-crystal of it in, and slowly drew out a ⅓ ton popsicle of ultrapure single crystal Si. Then, using saw blades, we sawed it up, polished it real good, got it to a bright mirror finish, packed 20 of them in a stack, and shipped them to the customer. Each popsicle yielded about 500 slices good enough to send to the chip makers.”

    Mmmm… I’m thinking the boron nitride-on-liquid-gold-in-a-hard-vacuum is kind of WAY more expensive. Way, way more. And not sounding like it could be readily mass-produced like the cut-up-silicon-popsicle method. 

    Moreover, how are the makers planning on cleanly transferring the film to something rather less expensive than a gold covered atomically flat tungsten blank?

    Just asking…

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