Going Direct: Researchers Change Skin Into Blood With No Stops in Between

By Jennifer Welsh | November 8, 2010 4:21 pm

bloodIt may not be as miraculous as turning water into wine, or as wealth-generating as turning dirt into gold, but we still think this is a very cool trick: Researchers have transformed mature skin cells directly into mature blood cells. Crucially, this was done without reverting the cells to a flexible, “pluripotent” stage in which the cells can grow into any form.

The technique, described in Nature, could lead to lab-grown blood cells for transfusions and transplants for people with bone marrow diseases. Researchers think this new process may be safer than previous methods.

By skipping the pluripotent step, the researchers believe they have skirted the risk that the replacement cells might form dangerous tumors. [Los Angeles Times]

The research team, lead by Mickie Bhatia, coaxed the skin cells into becoming blood cells via a harmless virus that carried a gene called OCT4 into the cells–this reprogrammed the cells, turning their developmental clock back part of the way. Then the cells were incubated in a mixture of cell-stimulating proteins, called cytokines, which directed them on their new paths as either red blood cells, white blood cells, or platelets. The ability to grow a specific kind of blood cell has exciting clinical possibilities.

“If the patient has anaemia, they only need red blood cells, so we can change the recipe and make those. If we wanted to treat someone with a blood coagulation disorder, we change the recipe again and make platelets,” said Mickie Bhatia. [The Guardian]

Bypassing the pluripotent cell stage has another advantage besides reducing the risk of tumor growth. Previous transformations that guided cells through an embryonic-like stage produced fetal blood, rather than adult human blood. This fetal blood has a different type of hemoglobin than adult blood, and holds tighter to oxygen. The new process makes adult blood, which is much more useful.

Being able to take one type of cell and turn it into another would be a great boon to patient-specific stem cell therapies. For example, doctors could take the skin cells of a leukemia patient and use them to make new, non-cancerous blood cells, instead of requiring a bone marrow transplant from a donor.

And while we can’t be sure how the human body will react to these lab-engineered cells, in Bhatia’s tests the transmogrified cells acted exactly like normal blood cells. The researchers tested the cells on mice and found that they didn’t cause stem cell-related tumors, called teratomas; the cells were also incorporated successfully into the animals’ bone marrows.

The ultimate test would be transplanting the cells into humans, says Bhatia, but that isn’t on the cards — at least not yet. “The clinical side is going to be a lot of work,” he says. “At least from our estimation, this is the most encouraging result we’ve seen for using blood cells for cell-replacement therapy.” [Nature News]

One of the worries about using these types of lab-engineered cells is that we might not fully understand what they are, if they differ from natural cells, and how they’d behave in a human being.

In particular, epigenetic modifications — changes that modify gene expression without altering the DNA sequence — could differ between blood cells produced naturally and those created by direct conversion. “The journey from a zygote to a specialized blood cell is very long. The journey from a fibroblast to a blood cell in a petri dish may take a very different route,” says [stem cell biologist George] Daley. [Nature News]

Related content:
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80beats: Gene Therapy Hope for HIV: Engineered Stem Cells Hold Promise
80beats: GE Plans to Use Human Embryonic Stem Cells as Lab Rats
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Image: iStockphoto

CATEGORIZED UNDER: Health & Medicine, Top Posts
  • k

    It’s probably just me, but thinking about a virus than can change skin cells to blood cells makes my flesh creep. So to speak.

  • Idlewilde

    I’m filing this away for future ‘vampires coexisting with humans’ stories…

  • questioner

    Can anyone shed light on what they plan to do about different blood types?

  • jd

    Antigenic determination in the source tissue for blood type?

  • j g

    anyone know the company that is behind this? I would love to invest some money with them this could be huge!!

  • jd

    McMaster University, Canada thank God.

    No doubt private corporate interests will want to control and commoditize this…
    The way “they” want to control water, food, information, eternal salvation…

    On the other hand, This could replace EPO as a lead “performance boosting” technology.
    Always a dark side.

    I hope the University has a plan.

  • blood doctor

    Regarding different blood types, the first and most significant application of this technology would be producing red blood cells for people who aren’t making their own, in other words for “autologous” transfusion—so you would have the type needed if the skin cells came from the patient. If you’re talking about mass producing banked blood for “homologous” transfusions, other factors come into play. The ABO system is only one group of antigens found on the red blood cell. Even if you get ABO matched blood, you can, after transfusion, develop antibodies to any of a variety of other antigens. No one has yet found a feasible method for stripping blood of all antigens to completely prevent this.

  • Devil’s Advocate

    I’m with K. What are the possible risks if the virus escaped the lab? I realize that cytokine incubation is necessary for the transformation into blood cells, but what does the intermediary step look like? If introduced onto the skin of a human, what would be the results?

  • Jennifer Welsh

    Hey all,

    Thanks for reading and commenting. Like all stem cell and induced pleuripotent stem cell work, we have no idea how these types of cells will act in humans. It is still all up in the air even what applications these types of cells may be used for.

    In response to the viral worries, it seems one important thing to remember is we are constantly infected by harmless viruses (just like our bodies are infested with bacteria). But I’m sure before any clinical trials start they will find a way to transform the cells without the viral infection.

    Just my thoughts.

    Jen

  • AJ in CA

    This is great news, and I understand that viruses can be useful for gene therapy and whatnot…
    But part of me can’t stop picturing that scene in “Raiders of the Lost Ark” there that guy’s face turns red and melts :P

  • Jimmy Cao

    Well it says “harmless virus” so I presume that if the virus infects a cell, that cell won’t change much at all, unless if the cell is exposed to those growth factors and cytokines.

  • Fred

    Well, considering the skin cells have their growth turned back a stage or three, opening up new development paths according to environment, I would imagine that any infection of a human would mostly result in the infected cells redevolping into the same type of cell. However, there would likely be some amount of mutation, and any cells at boundaries between cell types might develope particuarly oddly. This might result in tumors, though they might not be activly malignant as with cancers. This does not seem to be a serious problem in a healthy human, though, we have an immune system that would interfere with the virus’s propagation. Afterall, it protects us daily from very similar threats.

    Regardless, this is very interesting work.

  • Nate

    Didn’t they already make a game about this??? :D look out –<>–

  • Mike La Torres

    I’m guessing “harmless virus” refers to viral particles engineered not to carry viral genes: they can infect cells but can’t program them to make more viruses. You need specific lab conditions to produce them. They’ve been in use for a couple decades with zero “outbreaks”.

  • woundedduck

    What we really need is a pluripotent blow job. Seriously. Way before we do blood cells-from-skin cells.

  • Biologist

    Addressing the first issue of antigenic response: You could create the blood cells from the recipient. In other words if someone needs this therapy, you take their skins cells and convert them into the blood cells. All cells regardless of where they are in the body contain all the necessary genes to create any other cell. This means that when they are converted the cells will express the same surface antigens as the person’s natural blood cells. Another possibility would be to use universal donors. O- individuals express no surface antigens; and therefore, they can give blood to any individual.

    As for viral infection: It is not an infection ‘per se’. This simply means using a virus (DNA/RNA with a protein shell) to deliver genes into tissues. They use viruses because they can incorporate into the cells. However, they are engineered in a way (with certain promoters and specific genes) that only allow for the incorporation and expression of the wanted genes. These are also non-replicating and cannot spread to other nearby cells.

    Hope this clears some stuff up. This is really promising technology and is probably closer than you think with how fast technology is moving.

  • http://na Austin

    I can change skin into blood. I need some sandpaper and a volunteer.

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