Researchers create early stage sperm cells from induced pluripotent stem cells, raising hopes that infertile men could be fathers.

By Hayley Dunning | August 30, 2012

Men made infertile by cancer treatments could have their fertility restored by creating new sperm from their own skin samples, researchers at the University of Pittsburgh School of Medicine reported last week (August 23) in Cell Reports. While there is the opportunity for men to bank their sperm before undergoing cancer treatment, this doesnt help young, pre-pubescent boys or men who didnt plan that far ahead, lead author Charles Easley told The Telegraph.

There are procedures to store testicular tissue prior to cancer therapy, but men who didnt have the opportunity to save tissue are permanently sterile, and so far there are no cures for their sterility, he said.

Easley and colleagues developed an in vitro culture to generate human induced pluripotent stem cells from adult skin samples, and differentiate the cells into advanced male germ cell lineages, including post-meiotic, spermatid-like cells. The technique mirrors the in vivo process, and produces spermatids similar to human sperm.

This model also gives us a unique opportunity to study the molecular signals that govern the process, allowing us to learn much more about how sperm are made, said Easley. Perhaps one day this will lead to new ways of diagnosing and treating male infertility.

By Sabrina Richards

A small molecule that inhibits a protein important for chromatin organization can cause reversible sterility in male mice.

By Sabrina Richards

Researchers track tumors as they develop, providing more support for the idea that cells with stem-cell-like properties underlie cancer growth and recurrence.

Continued here:
Creating Sperm from Skin

In past years, these nine little letters, stem cells, have caused much controversy and misunderstanding.

Stem cells are primitive, undifferentiated cells that are able to divide and become specialized cells of the body such as liver cells, muscle cells, blood cells and other cells with specific functions.

Because they have not yet committed to a developmental path that will form a specific tissue or organ, they are considered master cells with great potential. You may have wondered about what they are used for, and if they hold promise for helping you or a family member with serious disease or injury.

Stem cells are interesting and useful to doctors and scientists for several reasons:

Further work includes potential treatment for Type 1 diabetes, arthritis, stroke, Parkinsons disease, heart disease and Alzheimers disease.

There are also cosmetic applications, using the patients own cells for facial and body enhancement, such as the stem cell facelift, and topical skin applications.

The different types of stem cells include:

These come from embryos that are four to five days old, usually left over from fertility treatments and voluntarily donated.

These were thought to have the most potential for scientific use because they had minimal exposure to potential environmental toxins and great potential for use in tissue and organ regeneration. They are able to self-renew and are pluri-potent, meaning they become any type of cell in the future.

Embryonic cells are also the source of great controversy and debate, since many of us believe that life begins at conception and that manipulation of embryonic stem cells is unethical.

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Positively Beautiful: Ever wondered about stem cells?

Stem cell-powered implant set to revolutionise orthopaedic surgery

Scientists at the University of Glasgow are working to harness the regenerative power of stem cells to improve orthopaedic implant surgery. They are collaborating with surgeons at Glasgows Southern General Hospital to develop a new type of orthopaedic implant which could be considerably stronger and more long-lived than the current generation of products.

Currently, implants are commonly made from materials such as polyethylene, stainless steel, titanium or ceramic and have a limited lifespan due to loosening, requiring replacement after 15 or 20 years of use. In hip replacement surgery, the head of the thigh bone is removed and replaced with an implant which is held in place by a rod fixed inside the marrow along the length of the bone.

Marrow is a rich source of mesenchymal stem cells, which have the potential to divide, or differentiate, into other types of cells such as skin, muscle or bone which can improve the process of healing. However, stem cells can also differentiate into cells which have no use in therapy. Artificially controlling the final outcome to ensure the desired type of cells are created is very difficult, even under laboratory conditions.

When traditional implants are fixed into bone marrow, the marrows stem cells do not receive messages from the body to differentiate into bone cells, which would help create a stronger bond between the implant and the bone. Instead, they usually differentiate into a buildup of soft tissue which, combined with the natural loss of bone density which occurs as people age, can weaken the bond between the implant and the body.

The team from the University of Glasgows Colleges of Science and Engineering and Medical, Veterinary and Life Sciences have found a reliable method to encourage bone cell growth around a new type of implant. The implant will be made of an advanced implantable polymer known as PEEK-OPTIMA, from Invibio Biomaterial Solutions, which is already commonly used in spinal and other orthopaedic procedures.

Dr Matthew Dalby, of the Universitys Institute of Molecular, Cell and Systems Biology, explained: Last year, we developed a plastic surface which allowed a level of control over stem cell differentiation which was previously impossible. The surface, created at the Universitys James Watt Nanofabrication Centre, is covered in tiny pits 120 nanometres across. When stem cells are placed onto the surface, they grow and spread across the pits in a way which ensures they differentiate into therapeutically useful cells.

By covering the PEEK implant in this surface, we can ensure that the mesenchymal stem cells differentiate into the bone cells. This will help the implant site repair itself much more effectively than has ever been possible before and could well mean that implants will last for the rest of patients life.

Dr Dalby added: People are living longer and longer lives nowadays; long enough, in fact, that were outliving the usefulness of some of our body parts. Our new implant could be the solution to the expensive and painful follow-up surgeries which conventional implants require.

Dr Nikolaj Gadegaard, Senior Lecturer in Biomedical Engineering at the University, explained: One of the main selling points of PEEK is that it is very strong, has excellent stability and is very resistant to wear. However, the inertness of the material is not always suitable for implants that require some interaction with the surrounding tissue. Our nanopatterned surface may allow Invibios PEEK polymer to interact with stem cells and enable an effective integration between the implant and the body for the first time.

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Stem cells power implants

ScienceDaily (Aug. 30, 2012) The skin, the blood, and the lining of the gut -- adult stem cells replenish them daily. But stem cells really show off their healing powers in planarians, humble flatworms fabled for their ability to rebuild any missing body part. Just how adult stem cells build the right tissues at the right times and places has remained largely unanswered.

Now, in a study published in an upcoming issue of Development, researchers at the Stowers Institute for Medical Research describe a novel system that allowed them to track stem cells in the flatworm Schmidtea mediterranea. The team found that the worms' stem cells, known as neoblasts, march out, multiply, and start rebuilding tissues lost to amputation.

"We were able to demonstrate that fully potent stem cells can mobilize when tissues undergo structural damage," says Howard Hughes Medical Institute and Stowers Investigator Alejandro Snchez Alvarado, Ph.D., who led the study. "And these processes are probably happening to both you and me as we speak, but are very difficult to visualize in organisms like us."

Stem cells hold the potential to provide an unlimited source of specialized cells for regenerative therapy of a wide variety of diseases but delivering human stem cell therapies to the right location in the body remains a major challenge. The ability to follow individual neoblasts opens the door to uncovering the molecular cues that help planarian stem cells navigate to the site of injury and ultimately may allow scientists to provide therapeutic stem cells with guideposts to their correct destination.

"Human counterparts exist for most of the genes that we have found to regulate the activities of planarian stem cells," says Snchez Alvarado. "But human beings have these confounding levels of complexity. Planarians are much simpler making them ideal model systems to study regeneration."

Scientists had first hypothesized in the late 1800s that planarian stem cells, which normally gather near the worms' midlines, can travel toward wounds. The past century produced evidence both for and against the idea. Snchez Alvarado, armed with modern tools, decided to revisit the question.

For the new study, first author Otto C. Guedelhoefer, IV, Ph.D., a former graduate student in Snchez Alvarado's lab, exposed S. mediterranea to radiation, which killed the worms' neoblasts while leaving other types of cells unharmed. The irradiated worms would wither and die within weeks unless Guedelhoefer transplanted some stem cells from another worm. The graft's stem cells sensed the presence of a wound -- the transplant site -- migrated out of the graft, reproduced and rescued their host. Unlike adult stem cells in humans and other mammals, planarian stem cells remain pluripotent in fully mature animals and remain so even as they migrate.

But when Guedelhoefer irradiated only a part of the worm's body, the surviving stem cells could not sense the injury and did not mobilize to fix the damage, which showed that the stem cells normally stay in place. Only when a fair amount of irradiated tissue died did the stem cells migrate to the injured site and start to rebuild. Next, Guedelhoefer irradiated a worm's body part and cut it with a blade. The surviving stem cells arrived at the scene within days.

To perform the experiments, Guedelhoefer adapted worm surgery and x-ray methods created sixty to ninety years ago. "Going back to the old literature was essential and saved me tons of time," says Guedelhoefer, currently a postdoctoral fellow at the University of California, Santa Barbara. He was able to reproduce and quantify results obtained in 1949 by F. Dubois, a French scientist, who first developed the techniques for partially irradiating planarians with x-rays.

But Guedelhoefer went further. He pinpointed the locations of stem cells and studied how far they dispersed using RNA whole-mount in situ hybridization (WISH), specifically adapted to planarians in Snchez Alvarado's lab. Using WISH, he observed both original stem cells and their progeny by tagging specific pieces of mRNA . The technique allowed him to determine that pluripotent stem cells can travel and produce different types of progeny at the same time.

Originally posted here:
Moving toward regeneration

Public release date: 28-Aug-2012 [ | E-mail | Share ]

Contact: Leslie Orr Leslie_Orr@urmc.rochester.edu University of Rochester Medical Center

University of Rochester Medical Center scientists believe they are the first to identify genes that underlie the growth of primitive leukemia stem cells, and then to use the new genetic signature to identify currently available drugs that selectively target the rogue cells.

Although it is too early to attach significance to the drug candidates, two possible matches popped up: A drug in development for breast cancer (not approved by the Food and Drug Administration), and another experimental agent that, coincidentally, had been identified earlier by a URMC laboratory as an agent that targets leukemia cells.

The research not only provides a better understanding of the basic biology of leukemia it uncovered genes not previously known to be associated with the disease -- but demonstrates a powerful strategy for drug discovery, said senior investigator Craig T. Jordan, Ph.D., the Philip and Marilyn Wehrheim professor of Medicine at URMC and the James P. Wilmot Cancer Center.

First author John Ashton, PhD, led the study, which was published this month in the journal Cell Stem Cell.

"Our work is both basic and translational, and is an example of a terrific collaboration," Jordan said. "We were able to use the latest technology to expand very strong basic laboratory concepts and conduct an intriguing analysis that may yield new insights for treatments of leukemia."

Jordan studies leukemia stem cells, which, unlike normal cells, renew uncontrollably and are believed to be the first cells at the root of malignancy. He collaborated with Hartmut (Hucky) Land, Ph.D. and Helene McMurray, Ph.D., investigators in the Biomedical Genetics Dept at URMC, who study the principle that cancer evolves from a unique, interactive network of genes that are governed by a distinct set of rules.

In 2008 Land's laboratory published a paper in Nature reporting on a pool of approximately 100 genes that cooperate to promote colon cancer. The Land laboratory coined the term CRG for "cooperation response genes," to emphasize the special synergy controlling this pool of genes. Land is the Robert and Dorothy Markin Professor and Chair of the Department of Biomedical Genetics at URMC, and co-director of the Wilmot Cancer Center.

The identification of CRGs broadened the view of cancer, Jordan said. Historically, scientists would study the intricacies of one or two individual pathways in a vast network of alterations. With the advent of CRGs, however, researchers now have a better picture of the sub-populations of genes that dole out instructions to primitive cancer cells, like controls on a circuit board. Depending on whether CRGs are turned off or on, patterns change and cancer either progresses or stops, Land's research showed.

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URMC researchers connect new genetic signature to leukemia

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