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
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.
Isn't the story eerily similar to the Macchiarini scandal at Karolinska from a few years ago? https://forbetterscience.com/2016/04/26/the-stem-cell-faith-... He also thought he could use adipose stem cells for implants but it didn't work and patients died. E.g if the new method causes implants not to be rejected that would indeed be a breakthrough, but many have tried and failed so one should be extremely skeptical about these claims.
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.
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?
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.
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.
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].
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.
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.
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.
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.
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. :)
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.
There are enzymes in cells called proteasomes that degrade intracellular proteins that are damaged, not needed anymore or just old and ready to be replaced. The rest products are peptides, short chains of amino acids, some of which become bound to molecule called the Major Histocompatibility Complex 1, which is then transported to and presented on the surface of the cell. It functions more or less as an ID badge of the cell. Foreign cells, cancerous cells or cells infested by bacteria or viruses will present unknown proteins, which will trigger an immune response.
An obvious solution would be to deactivate the MHC 1 in transplanted foreign tissue, but sadly that wouldn't work because the Natural killer cells in our immune system destroy cells without MHC 1. This is probably an adaption that evolved as bacteria evolved the capability to downregulate MHC 1 molecules to evade detection by other parts of the immune system.
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?
>- 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.
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?
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*
Well they do talk about using the implanted tissue to regenerate organs, which is pretty cool. But it still doesn't seem to render the headline accurate.
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.