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You’ve got a lot of nerve! Industrial-scale procedure for generating plenty of personalized nerve cells

You've got a lot of nerve! Industrial-scale procedure for generating plenty of personalized nerve cells

Embryonic stem cells (or ESCs) and their younger cousins the induced pluripotent stem cells (iPSCs) are prized because they can, alternatively, replicate themselves indefinitely in a dish or differentiate into every cell type in the body. This makes them potentially valuable tools for regenerative medicine.

And because iPSCs can be made from a person’s skin cells, manipulating their differentiated progeny lets investigators study disease processes at the cellular level, in a dish and in a personalized way. By custom-producing, for example, a given individual’s nerve cells,  researchers can study the specific defects of those cells in a dish, without having to first perform the ethically unthinkable – and, therefore, purely hypothetical – act of slicing chunks of tissue out of that person’s brain in order to do so. The researchers can, further, toss thousands of different compounds into thousands of tiny “wells” containing these nerve cells to see which ones might restore those cells’ proper function. (Different drugs are likely to work better with different individuals’ defective cells, depending on the nature of the cell’s defining defect.)

Scientists have successfully coaxed both ESCs and iPSCs down the developmental pathway to become nerve cells. They’ve even generated nerve cells directly from skin cells. But up to now, the procedures they’ve used have been plagued by two problems. First, quality assurance: The extent to which nerve cells generated by these methods actually look and act like nerve cells are supposed to look and act varies a lot, depending on which particular ESC line, or which iPSC line, was used to generate them. Second, the process is slow and the yield is low (it typically takes months to get from the beginning to the end, and many of the “starter” ESCs or iPSCs don’t successfully convert to decently functioning nerve cells).

But in a recently published paper in Neuron,  a team under the direction of Stanford cell physiologist and neuroscientist Tom Sudhof, PhD, has showed that just boosting the level, in human ESCs or iPSCs, of one single substance (a type known as a transcription factor) results in an abundant and quite pure population of nerve cells within as little as two weeks. And unlike previous methods, this one seems to generate nerve cells of equally high functional quality regardless of which “starter” cell line was used to get the process underway.

Clearly, if you’re doing regenerative medicine for a stroke or brain-trauma victim etc., you’re going to need a lot of nerve cells, and time is of the essence. So the new method represents a major forward step toward the realization of the dream of personalized regenerative medicine.

Previously: Revealed: the likely role of Parkinson’s protein in the healthy brain, Nervous breakdown: Preventing demolition of faulty proteins counters neurodegeneration in lab mice and Human neurons from skin cells without pluripotency?
Photo by Crystalline Radical

10 Responses to “ You’ve got a lot of nerve! Industrial-scale procedure for generating plenty of personalized nerve cells ”

  1. Kyle Furth Says:

    With so many cells being created, won’t it be that much harder to verify their quality?

  2. Jennifer Says:

    This article was a great find. Thanks, Bruce. I’ve got so much hope for these cells. Will this be able to help those with Parkinson’s?

  3. Chris Says:

    Scientific research always has it’s lulls and breakthroughs, the point is to keep a rational perspective on the state of it

  4. Nate Says:

    I feel like I’ve been hearing a lot about the “dream of personalized medicine”. But at the same time I feel like a lot of stuff goes unexplained. Things like cell lines and “pluripotency” are such ambiguous terms that are used loosely that’s it’s hard for any sort of casual observer to have a true grasp of what is going on.

  5. Chris Says:

    I agree, Nate. For me, it’s a matter of finding good sources. Wired and Forbes both offer quality subject matter in a digestable way.

  6. Tim Henry Says:

    Great point, Nate. I’ve recently begun doing my own research into it and found an article on Wired. http://bit.ly/13CXJMJ

    Hope it can put stem cell research into a different light.

  7. Bruce Goldman Says:

    In response to several thoughtful comments, a few points that I hope will be helpful.

    Kyle, the scientists in this case used a sophisticated selection method that ensured that a) only nerve cells would survive and b) that those nerve cells would report their new identities by, essentially, glowing. Then, they checked those cells for a number of markers that are defining characteristics of a specific class of nerve cells (excitatory ones, which make up about 80 percent of the nerve cells in our brains) as well as distinguishing morphological and functional features. If* you’re a scientist, I’d urge you to read the study itself, for which I provided a link in my post. (*If not, it’s going to be pretty tough sledding!)

    Nate, it’s certainly true that there’s been a lot of puffery in this field, albeit (I hope) less in the past few years as utopian pronouncements have given way to problem-solving efforts. As for the term “pluripotency,” correctly used it should be quite unambiguous: the ability of a stem cell to differentiate into every known mature lineage (at least to the extent this can be tested).

    Tim, the Wired “dictionary” is great. I would add, though, that while it’s definitely true that pluripotent cell can turn into cancer cells, you don’t have to be pluripotent to do that. In fact, the prevailing thinking is that it is stem or progenitor cells – none of them pluripotent – in our tissues that, when things go wrong, kick off the cancer process. Needless to say, you sure wouldn’t want to just shove a bunch of pluripotent cells into a patient’s body (even if they were derived from adult cells that came from the patient’s own body) and hope for the best. That’s why it’s so important that the cells you DO put in are of the more differentiated type you’re trying to replace. This is one reason why the Sudhof team’s apparent ability to generate large numbers of a very specific type of nerve cell that, by their testing, was 100 percent pure (beating all previous attempts) is such great news.

    Still a long, long way to go before this translates into cell replacement for stroke, brain trauma, Parkinson’s, you name it. But a step in the right direction.

  8. Kyle Furth Says:

    Not a scientist. Just someone with an intense interest in the science. Appreciate you taking the time to answer my question, thank you Bruce.

  9. Tim Henry Says:

    Thanks kindly for the response, Bruce. I read about Sudhof, but considering the production of so many cells, aren’t there concerns about having a much greater potential for unrecognized flaws?

  10. Chris Says:

    One question Bruce: what are you referring to as “utopian pronouncements”?

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