A team of haematologists has engineered a particular white blood cell to be HIV resistant after hacking the genome of induced pluripotent stem cells (iPSCs).

The technique has been published in the Proceedings of the National Academy of Sciences and was devised by Yuet Wai Kan of the University of California, former President of the American Society of Haematology, and his peers.

The white blood cell the team had ideally wanted to engineer was CD+4 T, a cell that is responsible for sending signals to other cells in the immune system, and one that is heavily targeted by the HIV virus. When testing for the progress of HIV in a patient, doctors will take a CD4 cell count in a cubic millimetre of blood, with between 500 and 1,500 cells/mm3 being within the normal range. If it drops below around 250, it means HIV has taken hold -- the virus ravages these cells and uses them as an entry point.

HIV gains entry by attaching itself to a receptor protein on the CD+4 Tcell surface known as CCR5.If this protein could be altered, it could potentially stop HIV entering the immune system, however. A very small number of the population have this alteration naturally and are partially resistant to HIV as a result -- they have two copies of a mutation that prevents HIV from hooking on to CCR5 and thus the T cell.

In the past, researchers attempted to replicate the resistance by simply transplanting stem cells from those with the mutation to an individual suffering from HIV. The rarity of this working has been demonstrated by the fact that just one individual,Timothy Ray Brown(AKA the Berlin patient), has been publicly linked to the treatment and known to be HIV free today. The Californian team hoped to go right to the core of the problem instead, and artificially replicate the protective CCR5mutation.

Kan has been working for years on a precise process for cutting and sewing back together genetic information. His focus throughout much of his career has been sickle cell anaemia, and in recent years this has translated to researching mutations and how these can be removed at the iPSC stage, as they are differentiated into hematopoietic cells. He writes on his university web page: "The future goal to treatment is to take skin cells from patients, differentiate them into iPS cells, correct the mutations by homologous recombination, and differentiate into the hematopoietic cells and re-infuse them into the patients. Since the cells originate from the patients, there would not be immuno-rejection." No biggie.

This concept has now effectively been translated to the study of HIV and the CD+4 T cell.

Kan and his team used a system known as CRISPR-Cas9 to edit the genes of the iPSCs. It uses Cas9, a protein derived from bacteria, to introduce a double strand break somewhere at the genome, where part of the virus is then incorporated into the genome to act as a warning signal to other cells. An MIT team has already used the technique to correct a human disease-related mutation in mice.

When Kan and his team used the technique they ended up creating HIV resistant white blood cells, but they were not CD+4 T-cells. They are now speculating that rather than aiming to generate this particular white blood cell with inbuilt resistance, future research instead look at creating HIV resistant stem cells that will become all types of white blood cells in the body.

Of course, with this kind of therapy the risk is different and unexpected mutations could occur. In an ideal world, doctors will not want to be giving constant cell transplants, but generating an entirely new type of HIV resistant cells throughout the body carries its own risks and will need stringent evaluation if it comes at all close to being proven.

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Stem cells edited to produce an HIV-resistant immune system

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Newswise (New York June 9, 2014) -- A protein may be the key to maintaining the health of aging blood stem cells, according to work by researchers at the Icahn School of Medicine at Mount Sinai recently published online in Stem Cell Reports. Human adults keep stem cell pools on hand in key tissues, including the blood. These stem cells can become replacement cells for those lost to wear and tear. But as the blood stem cells age, their ability to regenerate blood declines, potentially contributing to anemia and the risk of cancers like acute myeloid leukemia and immune deficiency. Whether this age-related decline in stem cell health is at the root of overall aging is unclear.

The new Mount Sinai study reveals how loss of a protein called Sirtuin1 (SIRT1) affects the ability of blood stem cells to regenerate normally, at least in mouse models of human disease. This study has shown that young blood stem cells that lack SIRT1 behave like old ones. With use of advanced mouse models, she and her team found that blood stem cells without adequate SIRT1 resembled aged and defective stem cells, which are thought to be linked to development of malignancies.

"Our data shows that SIRT1 is a protein that is required to maintain the health of blood stem cells and supports the possibility that reduced function of this protein with age may compromise healthy aging," says Saghi Ghaffari, MD, PhD, Associate Professor of Developmental and Regenerative Biology at Mount Sinai's Black Family Stem Cell Institute, Icahn School of Medicine. "Further studies in the laboratory could improve are understanding between aging stem cells and disease."

Next for the team, which includes Pauline Rimmel, PhD, is to investigate whether or not increasing SIRT1 levels in blood stem cells protects them from unhealthy aging or rejuvenates old blood stem cells. The investigators also plan to look at whether SIRT1 therapy could treat diseases already linked to aging, faulty blood stem cells.

They also believe that SIRT1 might be important to maintaining the health of other types of stem cells in the body, which may be linked to overall aging.

The notion that SIRT1 is a powerful regulator of aging has been highly debated, but its connection to the health of blood stem cells "is now clear," says Dr. Ghaffari. "Identifying regulators of stem cell aging is of major significance for public health because of their potential power to promote healthy aging and provide targets to combat diseases of aging," Dr. Ghaffari says.

Researchers from Harvard Medical School and Children's Hospital in Boston participated in the study.

About the Mount Sinai Health System The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient servicesfrom community-based facilities to tertiary and quaternary care.

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Mount Sinai Researchers Identify Protein That Keeps Blood Stem Cells Healthy as They Age

Scientists from Queen Mary University of London have shown that stem cell behaviour can be modified by manipulating the nanoscale properties of the material they are grown on - improving the potential of regenerative medicine and tissue engineering as a result.

Stem cells are special because they are essential to the normal function of our organs and tissues. Previous research shows stem cells grown on hard substrates go on to multiply but do not differentiate: a process by which the cells specialise to perform specific functions in the body. In contrast, stem cells grown on softer surfaces do go on to differentiate.

In this new study, published in the journal Nano Letters, the researchers used tiny material patches known as nanopatches to alter the surface of the substrate and mimic the properties of a softer material.

"By changing the surface properties like the shape of the substrate at the nanoscale level, we tricked the stem cells to behave differently," explains co-author Dr Julien Gautrot, from QMUL's School of Engineering and Materials Science and the Institute of Bioengineering.

The team tested different sizes of nanopatches - from 3 microns to 100 nanometres (about one thousandth of the diameter of a hair). The stem cells behaved as if they were on a soft surface when in contact with the smallest patches because they can't firmly grip them.

Dr Gautrot added: "This development will be useful when there's a need to create a rigid implant to be inserted into the body. Potentially, such nanopatches could provide a soft touch to the surface of the implant so that cells from the neighbouring tissues are not perturbed by such a hard material."

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Stem cells are a soft touch for nano-engineered biomaterials

NBC News -- Researchers have grown part of an eye in a lab dish, using a type of stem cell made from a piece of skin.

They said the little retina started growing and developing on its own an important step towards creating custom-tailored organs in the lab.

We have basically created a miniature human retina in a dish that not only has the architectural organization of the retina but also has the ability to sense light," said M. Valeria Canto-Soler, an assistant professor of ophthalmology at the Johns Hopkins University School of Medicine.

The team used cells called induced pluripotent stem cells, or iPS cells, which are immature stem cells whose powers resemble those of embryonic stem cells they can morph into any cell type in the body.

Theyre made by tricking an ordinary cell, like a skin cell, into reverting back into embryonic mode. Then the researchers activate genes to get the cell to redirect itself into forming the desired cells in this case cells of the retina.

To the surprise of the researchers, the cells started developing as if they were in a growing human embryo.

"We knew that a 3-D cellular structure was necessary if we wanted to reproduce functional characteristics of the retina, but when we began this work, we didn't think stem cells would be able to build up a retina almost on their own. In our system, somehow the cells knew what to do, Canto-Soler said in a statement.

The experiment may ultimately lead to technologies that restore vision in people with retinal diseases, she added.

Tests showed the cells responded to light, the team reported in the journal Nature Communications. "Is our lab retina capable of producing a visual signal that the brain can interpret into an image? Probably not, but this is a good start," Canto-Soler said.

Other teams have used iPS cells to make a piece of human liver and are using them to study a range of human diseases.

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Eye in a Dish: Researchers Make Retina From Stem Cells

Mice severely disabled by a condition similar to multiple sclerosis (MS) could walk less than two weeks following treatment with human stem cells. The study, which uncovers new avenues for treating MS, was don e at the University of Utah and published online on May 15th 2014, in the journal Stem Cell Reports.

The scientists we surprised and encouraged by their finding. When they transplanted human stem cells into MS mice, they expected no benefit from the treatment. They thought the cells would be rejected, much like rejection of an organ transplant. Instead, the experiment yielded spectacular results.

A release from the university quotes co-senior author, Tom Lane, Ph.D., a professor of pathology at the University of Utah, who began the study at the University of California, Irvine, as saying, My postdoctoral fellow Dr. Lu Chen came to me and said, The mice are walking. I didnt believe her.

Within a short period of time, 10 to 14 days, the mice could walk and run. Six months later, they showed no signs of slowing down.

This result opens up a whole new area of research for us to figure out why it worked, said co-senior author Jeanne Loring, Ph.D., director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla, California.

More than 2.3 million people worldwide have MS, a disease in which the immune system attacks myelin, an insulation layer surrounding nerve fibers. The resulting damage inhibits transmission of nerve impulses, producing a wide array of symptoms including difficulty walking, impaired vision, fatigue and pain.

Current FDA-approved medications slow early forms of the disease by dampening attacks by the immune system. In recent years, scientists have turned their attention to searching for ways to halt or reverse MS. Such a discovery could help patients with latter, or progressive, stages of the disease, for whom there are no treatments.

Results from the study demonstrate the mice experience at least a partial reversal of symptoms. Immune attacks are blunted, and the damaged myelin is repaired, explaining their dramatic recovery.

The way we made the neural stem cells turns out to be important, said Loring, describing the reason behind the novel outcome.

Prior to transplantation, Lorings graduate student and co-first author on the paper, Ronald Coleman, followed his intuition and grew the cells so they were less crowded on the Petri dish than usual. The change in protocol yielded a human neural stem cell type that turned out to be extremely potent. The experiments have since been successfully repeated with cells produced under the same conditions, but by different laboratories.

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Mice With MS Walk Again After Stem Cell Tx