
Israeli scientists develop tissue implants that won't be rejected - evo_9
https://www.israel21c.org/israeli-scientists-develop-implanted-organs-made-from-patients-own-cells/
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andy-fillebrown
This is interesting stuff but I don't think the article describes anything
groundbreaking. The cells used by the scientists in the article are called
adipose-derived stem cells and their applications are already well known in
the regenerative medicine industry. See
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668445](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668445)

The biologists I develop software with have been talking about adipose-derived
stem cells for over a year, so I was hoping the article was going to announce
a technological leap in organ manufacturing. It did not.

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azernik
The joys of press releases vs. actual scientific papers.

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pjschlic
The innovation is personalized hydrogels built to avoid rejection, not the
induced pluripotent stem cells which were re-differentiated into things. The
key was the structural materials which hold those cells.

[https://onlinelibrary.wiley.com/doi/10.1002/adma.201803895](https://onlinelibrary.wiley.com/doi/10.1002/adma.201803895)

~~~
andy-fillebrown
That makes sense but is hydrogel rejection really a thing? I thought hydrogels
were already safe from rejection because they don’t contain anything the
immune system sees as a threat. Same goes for collagen, no?

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claytonius
It seems to me that the main advancement here is that the native extracellular
matrix is being re-seeded with differentiated stem cells, as opposed to
ordinary tissue engineering which uses a manufactured ECM or tissue
transplants, which do not involve making stem cells.

There’s still a long way to go before organs can be engineered, even with this
tech. We will need much finer control over the delivery of differentiating
signal factors for pluripotent stem cells as well as ECM structure.

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riazrizvi
I thought we already had processes for taking pig organs to use as ECMs (by
chemically flushing them of cells) and then reseeding then with a patient’s
stem cells? If so then this discovery is about not requiring stem cells,
instead they have found a new reliable process to repurpose stomach cells,
which are obviously easier to harvest.

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claytonius
You're right that we could already re-seed decellularized pig ECMs with human
stem cells, but we have also already been able to derive stem cells from the
stomach. I think the main claim that they're making is that by deriving both
the ECM and the Stem cells from the patient, the resulting tissue engineering
scaffold is less immunogenic than other methods.

While this is somewhat interesting, they get into trouble by going on to claim
that they've been able to generate "functional cardiac, cortical, spinal cord,
and adipogenic tissue implants". From what I can see in the paper they saw
increased expression of a few markers associated with those cell types and
some minor electrical activity, etc.

The idea that differentiating stem cells into vaguely tissue-like phenotypes
is equivalent to being able to manufacture organs brings back memories of the
shenanigans that went down at UCL a few years ago [1].

1\. [https://forbetterscience.com/2016/12/21/birchalls-trachea-
tr...](https://forbetterscience.com/2016/12/21/birchalls-trachea-transplant-
trial-at-ucl-suspended-by-health-authorities/)

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trhway
>decellularized pig ECMs

why not 3d print the ECMs? Isn't it just basically collagen with some
fibrin/laminin thrown into? Do the decellularized ECMs not have any immunogens
left? Definitely isn't an issue with the printed ones.

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claytonius
Unfortunately even with just collagen we can see an immunogenic response that
is annoyingly exacerbated by UV cross-linking of the individual collagen
proteins. That's why many of the best manufactured ECMs are cross-linked using
a mixture of UV exposure and EDC-NHS. Without photolithography i'm not sure
you'd be able to get a resolution high enough to mimic native ECM structures.

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surgeryres
No one likes to talk about the potential side effects of stem cell therapy.
They express tissue factor, which increases after culture required for these
treatments. Tissue factor is highly thrombogenic and can cause blood clots.

[https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/1...](https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/sctm.18-0015)

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anfilt
Sounds like great news for damaged organs, but the article seems imply full
organs.

Like the first line is: "cutting the risk of an immune response to implanted
organs."

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HocusLocus
I feel threatened by this and consider my ability to reject tissue implants as
a last line of defense.

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biot
How does the immune system distinguish between native tissue and foreign
tissue?

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vibrio
Many ways you could a semester of immunology on this. High a level there are
molecules called MHC (Major Histocompatability Complex), or HLA (Human
Leukocyte Antigen). They are very important to the immune system in a number
of ways. Any individual has a few sets of these, and there are many different
genetic types of these molecules so the differences between any two people can
be many. The immune system is even sensitive to their absence, since their
down regulation is a strategy for some pathogens such as virus. Anyway, as the
name MHC suggests, this is one way that the immune system detects foreign
tissue.

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weberc2
Apologies for an unsubstantial comment, but biology blows my mind.

Do we know when these features in our immune system evolved? I assume
something this foundational is shared with fish or maybe earlier?

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reubenswartz
Vertebrates have an adaptive immune system. It’s astounding from a biological
and information theory perspective. Genes basically mutate themselves so they
can form an enormous variety of proteins instead of the typical one to one
mapping of gene to protein. Then there is a protein selection process that
weeds out those antigens that bind to the host of that don’t bind to anything,
leaving those that can bind to foreign proteins. (There’s another process to
replicate antigens when they attack something.)

At least, that’s my primitive understanding. Come on HN, please someone fill
in the real story, because I’d love to understand it better. :)

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vibrio
I think you described it pretty well. my version of the same: During their
development Lymphocytes have 'gene cassettes' that get shuffled randomly so
that the specificity of the receptor (antibody for cells, T cell receptor for
T cells) is random for each individual lymphocyte cell during development. The
ones that bind "Self" stuff are killed off during their development and the
rest of them other just hang out waiting for something that binds their
receptor. (There is a step here where T cells must bind to MHC within an
affinity window to survive) If they find it the reproduce rapidly making many
more cells with that specify. once amazing thing is that during that cell
replication at the sites of antibody specificity the DNA copying gets sloppy,
allowing new mutations to 'fine tune' the specificity of the antibody to the
antigen (called somatic hypermutation). The cells that bind the tightest to
the foreign antigen, reproduce the most robustly providing an 'evolution' of
increasing affinity to the antigen. This stuff is only the tip of the iceberg
- immunology it is amazing.

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youeseh
Broadly speaking, does this mean that all we have to do now is figure out how
to rejuvenate the brain and spinal chord because everything else is
replaceable?

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effnorwood
They didn't

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car
The title is totally misleading.

\- The 'implants' are not organs.

\- The cells being implanted are from the recipient, so they naturally won't
be rejected.

If the headline were true at all, we'd be reading about this in one of the big
journals.

Edit: changed transplant to implant

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24gttghh
>\- The cells being implanted are from the recipient, so they naturally won't
be rejected.

Well, they appear to have engineered a patient's own cells into stem cells
which were then re-implanted into a patient(s).

>“We were able to create a personalized hydrogel from the materials of the
biopsy, to differentiate fatty tissue cells into different cell types and to
engineer cardiac, spinal cord, cortical and other tissue implants to treat
different diseases,” said lead researcher Prof. Tal Dvir

>The researchers extracted a small biopsy of fatty tissue from patients, then
separated its cellular and a-cellular materials. While the cells were
reprogrammed to become induced pluripotent stem cells — able to make cells
from all three basic body layers, so they can potentially produce any cell or
tissue the body needs to repair itself — the extracellular material was
processed to become a personalized hydrogel.

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lou1306
The title is about "organs", but the article apparently refers to tissue
transplants? No small feat, don't get me wrong, but isn't it a little
misleading?

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yohann305
you're right, there is a difference between organs. Tissue make up organs just
like amino acids would make proteins.

Here is a clear explanation:

The difference between cells, tissues and organs. A group of cells working
together is defined as a tissue and several tissues working together comprise
an organ*

source: [https://www.merckmanuals.com/home/fundamentals/the-human-
bod...](https://www.merckmanuals.com/home/fundamentals/the-human-body/tissues-
and-organs)

