Welcome to the modern era of induced pluripotent stem cells. 2012 Nobel Prize With just a little cocktail, usually of transcription factors, you can make one type of cell turn into another. usually, you will convert it to a less differentiated (cells are created in a sort of tree structure where the leaves are more and more specialized) form, which can then be pushed to develop into other specialized forms.
This is really common in the lab now. You can use them to create organoids which are like mini-organs that have a lot of the properties of, say, a lung or a liver or a stomach or a brain, but aren't a full organism. Very useful for making models of mammalian biology.
By the way the discovery that led to this was a huge surprise (at least, that so few factors were required to transform cells) but there is still very little known, IE we can't arbitrarily convert one cell type to another reliably. Culturing mammalian cells is pretty hard.
i'm trying to learn more about this space as i have a few friends working on building brain-like organoids, converting different types of neural / glial cells to other types, etc
seems like this stuff is mostly at the basic science stage, with main applications being better disease models (which in neuro is huge). do you have a sense for how far along these are translationally? do the cultured / expanded cells build up lots of mutations? can you induce specific neural cell types, or at least consistently end up with daughter cells that have the same function as their parents? are these processes scalable beyond the quantities needed for this initial work? are there quality methods in place for determining the identity and function of these cells?
Targeting cancer cells is hard. One of the functions of the immune system is to clear out pre-cancerous disease and error state. Cancer proliferates because it evolves in situ to evade immune regulatory checks.
One of the reasons stem cell technology is moving so slowly is that, apart from mammalian cell culture being hard, we're extremely anxious about messing with the growth pathways. Tripping up the gene expression is what causes cancer in the first place. We're trying to find exploits in the same machinery to induce novel transformations without kicking the cell into unregulated growth. It's going to be a long time before I let something like that into my body.
You make a bunch of solid points, IMHO, but to your last sentence - If I’m facing dying due to a neurodegenerative disease, I’d be willing to roll the dice on the possibility of cancer. Facing death seems like a powerful disinhibitiory driver to me....
I had a neighbor that was working on this to fix cartilage in race horses. They take connective tissue cells from the horse with bum knee, multiply them, turn them back into stem(ish) cells by exposing them to a series of chemical signals, purify them, and then inject them back into the injured area. They were stem(ish) cells because they would only ever turn into connective tissue, which was a guard against them turning into the wrong thing. He said full on stem cells had a tenancy to turn into cancers if used for this process. The purification process was the hard part, they had special plastic sheets that would stick to only the right kind of cells, they wash the cells over the sheet and then check with the microscope to make sure they only have good ones. Very tedious process, but a race horse is worth enough money to make it possible.
All my personal knowledge on this subject is like 6 years out of date. It appears there are companies now offering this for humans but I have no way of telling if they are legit.
To be clear though, This was a nuts concept until Yamanaka blew everyone's minds.
When I read cell biology texts in 2008 the "dogma" was that differentiation was a one way route.
I've had the pleasure of attending classes by a prominent stem cell person who presided over the conference session where Yamanaka presented his findings first. Apparently everyone just thought he was nuts. People only believed it when the original cell paper came out. Definitely one of my favorite biology papers of all time!
Just a general heads-up: the rest of the world hasn't quite noticed this yet, but it seems like biology has turned into a blink-and-you'll-miss-it science of rapid breakthroughs in the last decade.
I mention this to people and they stare sort of blankly at me. I point out that computers started taking the process in the 70's with the advent of new ways to make them cheaply. But it wasn't until the 90's, 20 years later, that "regular" people started seeing a benefit in owning a computer and how many things they could do. Then over the next 20 years that changed nearly everything about our world and continues to this day although it is slowing down a bit.
Similarly with cell biology which now has enough tools in the toolchest to do amazing things, and every year there is a new technique, a new finding, a new way of putting together the tools.
I really think this will materially change everyone's quality of life when we've got much of the cell manipulation down to engineering rather than science. Organ replacement, cures for illnesses that are incurable, and generally better health for everyone. But its 40 years away at this point before its "common for everyone"
Probably at least a decade. I remember hearing about it towards the beginning of the century. It is one path towards a less controversial acquisition of stem cells.
"Common"? Like you can actually just transform differentiated cells into stems cells into other differentiated cells willy-nilly? I thought this was still being worked on.
After spending several years using various methods to deliver small molecules in the mouse brain in vivo, we have not achieved definitive success of chemical conversion inside mouse brains despite the observation of a few neurons after chemical treatment. This is rather disappointing, but we are still continuously trying direct in vivo chemical conversion in the mouse brain. The biggest challenge for in vivo chemical conversion is how to maintain a constant concentration of small molecules inside the brain without causing a severe invasive damage to the brain. We have tried using biomaterial to encapsulate small molecules, but, perhaps because our small molecules are too small or we have not found the right biomaterial for such small molecules, the small molecules we applied might not stay for a long time inside the brain. We also tried an osmotic minipump (Alzet) but the tip of the insertion caused significant tissue damage inside the brain, and the injury induced many DCX+ cells that were mainly reactive astrocytes 2 weeks after drug treatment (Figures S7I–S7K).
Shame, but this is an entirely understandable problem, and these are still early days!
On the other hand, during our vigorous testing of in vivo chemical reprogramming, we accidentally found that core drugs significantly increased adult neurogenesis in the mouse hippocampus (Figure 7). We initially injected core drugs through intracranial injection into the hippocampus and sacrificed the mice 7 days later (Figure 7A). We observed remarkable increase of DCX-labeled newborn neurons together with Ki67-labeled proliferative cells in the dentate granule layer (Figures 7B–7E).
So, not conversion of glia into neurons, but production of new neurons from progenitor cells. That's still really useful! The hippocampus is what gets whacked in a load of different brain disorders (wikipedia tells me Alzheimer's and other dementias, PTSD, schizophrenia, and depression, for starters), so being able to drive neurogenesis there sounds really useful.
its still debatable however if there is neurogenesis in the human hippocampus so not sure if this method results are transferable. it would be cool if it worked generally though. alzheimer's causes neuronal loss throughout the cortex, while parkinson's mostly on dopaminergic neurons.
So the paper describes a way to make new neurons. Any indication that adding new neurons will actually improve cognitive abilities? I know nothing about neuroscience, but I could see a scenario where it is analogous to adding a computer to a computer room, with nothing on the hard drive, and no network connection.
If it's anything like an artificial neural network, adding new neurons or new neuron connections likely causes degradation in the overall abilities of the NN. Having neurons and connections is important, but the connections themselves have to be learned, selected, pruned to have overall value to the system.
I too would like to know more. Extending on the computer analogy, even if it is just adding more blank drives — does that mean your brain has additional _capacity_ for cognition?
Or is it more like those people who inject oil into their muscles in an attempt to look more buff without the work (and often end up looking grotesque instead).
i think most applications of neuronal cell therapy or regenerative medicine have focused on thinks like stroke. my understanding of the field is limited, but from what i understand the current tools are sort of blunt instruments. there are a huge amount of subtypes of neurons, and i dont think we are able to exert detailed control over which subtypes of neurons are created, and i think that after a certain number of divisions neural stem cells "forget" their subtype
i also dont think we understand enough about the biology of cognition to know how many of what kind of neurons to put where. not to mention any adverse effects, like synapses forming with non-target neurons, etc
It might be really useful to try to repair some non-cognitive areas of the brain. I.e. grow some new neurons to implant in the motor cortex that can relearn how to control limbs for people who had damage there.
Exactly, or what about strange new memories, i guess it would depend wholly on what layer of the neocortext the cell was converted on, but still, it could be very interesting.
Although it’s possible to change cells, once a cell has taken a form, it’s used resources. Having a cell shift to a new form seems nuts.
It may be possible, but I’m dubious. I find it more likely that their experiment(s) were contaminated, which seems relatively easy to do in this case.
Anyone with more experience have any thoughts?
I minored in bioengineering, but that was years ago, so I have limited knowledge.