Scientists convert skin cells into mature blood cells

Canadian researchers have succeeded in transforming human skin cells into different types of blood cells. McMaster University scientists have achieved a feat that might one day help patients who need blood transfusions for surgery, potentially treat deadly blood disorders, or to offset the destructive side-effects of chemotherapy. Additionally it also raises the possibility that other cell types, like neurons to repair brains damaged by disease or injury, could also be directly induced and grown in the lab using a mere scrap of a person’s own skin. The principal investigator, Mick Bhatia, the scientific director of McMaster’s Stem Cell and Cancer Research Institute, said his team was able to produce oxygen-carrying red blood cells, two kinds of immune cells and megakarocytes, the cells that generate platelets which are required for blood clotting.
This research has an additional significance in that these scientists were able to coax mature blood cells from skin without passing them through the intermediate step of producing stem cells that would then need to be differentiated into the various blood cell types. While blood cells can be made from either embryonic stem cells or induced pluripotent stem (iPS) cells, the process is far more complicated and time-consuming, as well as being fraught with potential safety problems. Such blood cells would also be “fetal” in nature, and not mature adult cells. These fetal blood cells would have properties that make them unsuitable for transfusion.
Bhatia said: “Because we were starting out with adult fibroblasts (skin cells), we actually made adult blood, which we are predicting is going to be far more useful.”
Skin cells used to generate blood cells came from six individuals who ranged in age from newborn to 65-plus. Apparently, the age of the donor did not matter. Scientists were able to convert all of the human skin cells to blood no matter how the age of the patient. When they transplanted these blood cells into lab-bred mice, they did not cause tumors, and behaved as normal red blood cells.
Dr. Cynthia Dunbar of the U.S. National Heart, Lung and Blood Institute said no one has been able to produce mature adult blood cells from embryonic or iPS stem cells, so the McMaster team’s ability to beget them — while detouring around stem cells — is an extremely exciting achievement. “The ability to do this is going to open a lot of doors in terms of being able to study biology,” Dunbar said from Bethesda, Md. “In terms of whether it’s going to be put into patients in the next five years, I think that’s very unlikely. But that doesn’t take away from how important it is scientifically and how important it is conceivably for eventual clinical applications.”
Cancer treatment is one area in which a supply of healthy blood cells is critical. This technique could potentially provide a new source of non-cancerous blood replacement for people with leukemia, who now rely on bone marrow transplants. For patients with solid organ tumors who are taking high doses or a prolonged regimen of chemotherapy, being able to generate new blood cells from a patient’s own skin would mean not having to interrupt treatment when the drugs begin destroying the blood system.
Pauses in anti-cancer treatment in order to give the patient time to recover and make new red blood cells can give the tumor time to grow out and spread throughout the body. Therefore another major advantage of this discovery is that physicians can provide the patient with new blood cell progenitors while continually treating the patient with chemotherapy.”
It might even be possible to freeze red blood cells and those that produce platelets created from the skin of people with rare blood types, not only for personal use but also for others with the same blood signature who need a transfusion. The McMaster team also plans to use the cells for testing experimental drugs, in what he calls “a clinical trial in a dish.”
There are, of course, a number of hurdles to overcome: finding a way to produce large quantities of the cells, ensuring their safety and seeking regulatory approval for their use. The team also has to determine the proper recipes for pulling out other cells that make up blood, including key disease-fighting white cells.
Still, Bhatia and his colleagues are already moving ahead — determining what other cellular building blocks of the human body they can draw from skin. “So we’re hoping this is not just limited to blood,” he said. “We’re hoping we can also get other cell types (and) we already have encouraging evidence.”

Harvard stem cell researcher retracts two papers

Harvard Medical School stem researcher Amy Wagers, who works at the Joslin Diabetes Center has issued a retraction notice for a 2010 paper, and has also issued a “statement of concern” in which she intends to review a second paper from 2008. One of her former postdoctoral fellows, Shane Mayack, was the first author on both of these papers, and she maintains the validity of the results reported in these papers.

On October 13, 2010, Wagers and two other authors retracted their January 2010 paper “Systemic signals regulate ageing and rejuvenation of blood stem cell niches.” This paper reported data that they interpreted to mean that stem cell aging processes might be reversible but the notice references “serious concerns” with the data that led to that hypothesis, which prompted the retraction.  Wagers has even issued a statement that upon reviewing the data from the Nature paper, she immediately notified Nature, JDC, and HMS that she and her colleagues have begun to repeat the experiments to test their validity.

A point of concern for Wager is the appearance of very similar figures in both papers; Figure S3b from the Nature paper and Figure 6c from the Blood paper chart the frequency of blood stem cells but result from very different protocols.  A day later, Wagers published a notice of concern in the journal Blood that stated that a 2008 paper that she coauthored with Mayack is also under review for possible misreporting of the data.  No further information has yet been published concerning the study, “Osteolineage niche cells initiate hematopoietic stem cell mobilization,” which features a figure that is strikingly similar to one published in the retracted Nature paper.

Although Mayack has not personally commented on the retractions, her lawyer issued a statement saying that although Mayack realizes the data presentation was improperly handled, she believes the underlying research remains conclusive. Accordingly, Mayack did not sign the retraction notice. Further examination is ongoing to determine if the conclusions presented in either paper are still viable.

At this point it is hard to say, but it seems possible that this is just a mix-up.  Hopefully, work from Wager’s lab will determine if the conclusions are justified.  Academic misconduct is a problem is science these days.  The most notorious case is that of South Korean researcher Professor Woo Suk Hwang,  However it is exceedingly hard to say if this case falls under this category.  My feeling is that the jury is still out on this one.  It is better to give the researchers the benefit of the doubt, given the information in hand.  As things develop, there will be more to say.