The blog of Xeno, a slightly mad scientist
Image: photoshop age progression – link.
A paper published in Nature today1 could dispel a cloud over the hopes of turning a patient’s own cells into perfectly matched replacement tissues.
Scientists first reported in 2007 that a person’s cells could be reprogrammed to an embryo-like state, and so could form any type of cell in the body. Medical researchers immediately imagined using these ‘induced pluripotent stem (iPS) cells’ to create an endless supply of genetically matched replacement tissues to treat a range of diseases: fresh pancreatic tissue for diabetics, for example, or new nerve cells for people with Parkinson’s.
The strategy also seemed to offer a way around the ethical complexities of using stem cells derived from human embryos. But then came the worries about possible side effects. Particularly bad news came from a 2011 study2 showing that iPS cells provoked immune responses when injected into the mice from which they had been derived, casting doubt over one of the key advantages of the cells.
The latest Nature study1 rejects that conclusion. Masumi Abe, a geneticist at the National Institute of Radiological Sciences in Chiba, Japan, and his team took iPS cells derived from mice and injected them back into the animals. For comparison, they injected other mice with embryonic stem (ES) cells. Yet unlike the 2011 study, which saw iPS cells perform worse than ES cells, the team found no differences between the immune responses of each group. The researchers also transplanted skin and bone-marrow cells derived from iPS or ES cells into mice and achieved similar success rates between the groups. The immune response of both sets of tissues is “indistinguishable”, says Abe.
Konrad Hochedlinger, a stem-cell scientist at Massachusetts General Hospital in Boston, says that the result will probably “calm people down” about iPS cells. “It is definitely reassuring,” he says.
The findings follow another positive study on iPS cells, published late last year3, which found that the reprogramming process causes fewer mutations than previously thought. Flora Vaccarino, a neuroscientist at Yale University in New Haven, Connecticut, and her colleagues used high-resolution DNA analysis to compare the genomes of iPS cells and the adult cells from which they were derived. They found that most of the DNA mutations in the iPS cells did not arise during reprogramming but had been present in the parent cells.
“The result will probably calm people down. It is definitely reassuring.”
Yang Xu, a stem-cell scientist at the University of California, San Diego, and co-author of the 2011 study2, says that the new work does not dispel all concerns about the immune response provoked by iPS cells.
Xu points out that the skin and bone-marrow cells used in the latest study were not grown from iPS cells in culture, as they would be for clinical use. Instead, the researchers mixed iPS cells into early mouse embryos to make ‘chimaeric’ embryos. They then used skin and bone-marrow tissues that arose from iPS cells after the embryos grew into adult mice for their transplantation experiments. It is possible, says Xu, that the most immunogenic cells were rejected as the mice developed, which would explain why Abe and his colleagues observed a limited immune response. Transplanting tissues from chimaeric mice is “flawed”, he says.
Producing chimaeric embryos is a standard technique for testing whether mouse iPS cells have been fully reprogrammed, says Jakub Tolar, a clinician at the University of Minnesota in Minneapolis, but he notes that differentiating cells in culture outside the body is much harder. Tolar, who hopes to use iPS cells to treat the childhood skin disease epidermolysis bullosa, adds that iPS-cell therapies will use human cells, which could behave quite differently from mouse cells. “It’s helpful that they’ve done this, but it is absolutely different when you go to something that is cultured,” he says.
Hochedlinger believes that iPS cells are just as promising for cell transplantation as ES cells, although many issues stand between the lab and the clinic. The differences between the two kinds of stem cell are minor compared with the differences in how individual cell lines grow and differentiate in culture, he says.
“Based on what we know at this time from mice,” he says, “iPS cells are as good as ES cells, and should be as safe.”
A few days after Christmas this year, I lost a family member to that most deadly of uncured human diseases: aging. Studies like this one are a reminder that some of us might be able to significantly delay the grim reaper within our lifetimes. Support SENS research:
SENS is an acronym for “Strategies for Engineered Negligible Senescence”. It is best defined as an integrated set of medical techniques designed to restore youthful molecular and cellular structure to aged tissues and organs. Essentially, this involves the application of regenerative medicine to the problem of age-related ill-health. However, regenerative medicine is usually thought of as encompassing a few specific technologies such as stem cell therapy and tissue engineering, whereas SENS incorporates a variety of other techniques to remove or obviate the accumulating damage of aging. This broadly defined regenerative medicine – which includes the repair of living cells and extracellular material in situ – applied to damage of aging, is what we refer to as rejuvenation biotechnologies.
Currently, SENS comprises seven major types of therapy addressing seven major categories of aging damage, and you will find details of these therapies throughout this section of the website. It is important to understand that these seven ‘planks’ are a description of SENS, rather than a definition, and could, in theory, change or grow as we progress in our research efforts and deepen our understanding of the challenges which face us, and their solutions. This is one of the reasons that we increasingly refer to rejuvenation biotechnologies in relation to our work.
Beware the many false claims of grey hair reversal. No one on Amazon, for example says that He Shou Wu does a bit of good. However, hair color has already been restored in mice:
Hair colour is determined by hair follicle stem cells working in conjunction with colour producing stem cells known as melanocytes. But now scientists have identified the signalling protein that coordinates pigmentation in the two cell types, which is known as Wnt. A lack of the protein in melanocyte stem cells leads to grey hair, according to a team of researchers from New York University Medical Centre, writing in journal Cell. Professor Mayumi Ito said that genetically manipulating the Wnt signalling proteins could stop hair turning grey, and that her team had found a method to successfully restore hair colour in mice. Prof Ito said: “We have known for decades that hair follicle stem cells and pigment-producing melanocyte cells collaborate to produce coloured hair, but the underlying reasons were unknown. “We discovered Wnt signalling is essential for coordinated actions of these two stem cell lineages and critical for hair pigmentation.” It is hoped that the research could give insights into diseases involving melanocytes, including melanoma.
Gray hair is, along with premature balding, one of the greatest fears of image-conscious men and women everywhere, but it may soon be a thing of the past. Scientists at the Ito Lab at New York University’s Langone Medical Center have identified the proteins that cause gray hair, which could lead to an eventual cure.
Scientists have known for years that hair color is determined by the stem cells that guide the development of hair follicles working together with color-producing stem cells called melanocytes. Today, NYU researchers announced they had isolated the wnt protein, which serves to coordinate pigmentation between the two types of stem cells.
Already, scientists have managed to start with black mice and once they inhibited the Wnt pathway in their melanocyte stem cells, they eventually turned gray.
“Mouse and the human hairs are very similar in the way that they are structured and the way they contain melanocyte stem cells. We found that the wnt signaling pathway is activated the same way,” said Piul Rabbani, a grad student in NYU’s Langone Medical Center who led the study, told ABC News.
via ABC News
Grey hair looks great on some people and I only pick on it here because it is one of the most obvious signs of aging that we might reverse with breakthroughs in stem cell research.