Figure 1: Neuroblasts localize polarity complexes (green) on the epithelial side (top) and divide perpendicular to the epithelium in a normal Drosophila embryo (scale bar, 10 m). Credit: 1 2012 Elsevier Inc.

Animals consist of many distinct cell types, all of which originate during development from a single cell: the fertilized egg. To generate this vast cellular diversity, the egg and its descendants must divide unevenly to produce new cells with different fates. Nowhere is this process more important than in the central nervous system, where the asymmetric division of neural stem cells called neuroblasts contributes to the profusion of neurons and glial cells.

Several proteins assemble into so-called polarity complexes that localize at one end of the neuroblast to help guide this unbalanced division (Fig. 1). But the mechanism that controls the orientation of these complexes has remained elusive. Now, a team of RIKEN biologists has discovered the master regulator that directs how these proteins are laid down in the neuroblasts of developing fruit fly, or Drosophila, embryos.

Fumio Matsuzaki and his colleagues at the RIKEN Center for Developmental Biology, Kobe, screened various mutant Drosophila embryos for defects in neuroblast polarity. They uncovered an important player in this process: a gene called trapped in endoderm 1 (Tre1), which encodes a transmembrane receptor protein. In a series of experiments with fly strains in which they deleted the Tre gene, the researchers showed that this receptor is necessary to orient the polarity of the protein complexes in a perpendicular direction relative to the neighboring epithelial cell layer.

Further dissections of proteinprotein interactions revealed that Tre1 recruits and orthogonally orients a critical polarity complex, known as Par, through a cascade of apically localized protein intermediaries. First, Tre1 activates a subunit of an important signal transducing molecule to recruit the protein Pins, which regulates spindle orientation. Another protein, called Inscuteable, then acts as a molecular link between Pins and Par to ensure that every component is in the proper location.

The Par-complex is known to regulate the formation of cell polarity in various cell types including stem cells and neurons, explains team member and co-author Shigeki Yoshiura. So this process might be involved in the orientation of the polarity of various cell types during development.

With Tre1 emerging at the top of the hierarchy controlling the orientation of polarity complexes in the neuroblast, Matsuzaki and colleagues are turning their attention to finding its regulator. We still do not know which molecule or molecules act as the extrinsic signal from epithelial cells, Yoshiura says. The RIKEN team is also investigating whether this mechanism is conserved through evolution and is applicable to mammalian neural stem cells.

More information: Yoshiura, S., et al. Tre1 GPCR signaling orients stem cell divisions in the Drosophila central nervous system. Developmental Cell 22, 7991 (2012).

Provided by RIKEN

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Central nervous system stem cells shed light on mechanism that controls asymmetrical division

Thirty Percent of Patients Show Improved Functioning after Stem Cell Therapy

Philadelphia, Pa. (May 17, 2012) One of the first long-term studies of stem cell treatment for spinal cord injury shows significant functional and other improvements in three out of ten patients, reports a study in the May issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

The results support the safety of mesenchymal stem cells (MSCs) derived from the patient's own bone marrow, showing "continuous and gradual motor improvement" in at least some patients with disability caused by spinal cord injury. The lead author of the new study was Dr. Sang Ryong Jeon of University of Ulsan College of Medicine, Seoul, South Korea.

Evidence of Improved Function after MSC Treatment for Spinal Cord Injury The researchers performed MSC transplantation in ten patients with permanent motor (movement) deficits or paralysis (paraplegia or quadriplegia) after spinal cord injury. Mesenchymal stem cells are a type of "multipotent" cell that can be cultured from adult bone marrow and induced to develop into many different types of cells.

The cultured MSCs were injected directly into the injured spinal cord and the surrounding (intradural) space. Additional cells were injected after another four and eight weeks. The results were assessed by measuring improvement in the patients' ability to move their arms and hands and to perform key activities of daily living. Imaging scans and tests of muscle activity were performed as well.

During the first six months after MSC transplantation, six of the ten patients showed improvement in motor power of the arms and hands. Of these, three patients had gradual improvement in the ability to perform daily activitiesfor example, preparing meals and typing on a keyboard.

These three patients also showed significant changes on MRI scans of the spinal cord, including evidence of healing around the injured area of the spine. They also had improvement in electrophysiologic studies of muscle electrical activity.

No Long-Term Safety Problems of MSC Transplant None of the ten patients had any permanent complications related to MSC transplantation. This helps to alleviate concerns that MSC injection could lead to later problems like the development of tumors or calcifications.

Previous studies have shown promising results with MSC transplantation in animals and humans with spinal cord injury. Mesenchymal cells have some important potential advantages for stem cell therapy, as they are a relatively easily accessible source of the patient's own cells. The ten patients treated by Dr. Jeon and colleagues represent the first attempt at direct spinal injection of MSCs for the treatment of spinal cord injury in humans.

Following up on a previous study reporting initial improvement in six patients, the new paper describes continued improvementincluding meaningful gains in the ability to perform everyday functional tasksin three patients. Dr. Jeon and colleagues note that all three patients with progressive improvement had some "residual neurological function." They write, "Therefore, MSC treatment is more likely to enhance the remaining neurological function rather than rengeneration." They call for further studies to understand the mechanism of improvement after MSC treatment and to clarify which patients with spinal cord injury are most likely to benefit.

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Stem Cells for Spinal Cord Injury: Some Patients Have Long-Term Improvement

MARLBOROUGH, Mass.--(BUSINESS WIRE)--

Advanced Cell Technology, Inc. (ACT; OTCBB: ACTC), a leader in the field of regenerative medicine, announced today that chairman and CEO Gary Rabin will be presenting at the World Stem Cells and Regenerative Medicine Conference, May 21-23, in London.

Mr. Rabins presentation, titled Successes and ongoing advancements of human clinical trials for the treatment of AMD & Stargardts Disease, will be given on Monday, May 21 at 5:05 p.m. BST (London time). Mr. Rabin will provide an update on ACTs three ongoing human clinical trials in the U.S. and E.U. for Dry Age-Related Macular Degeneration (Dry AMD) and Stargardts Macular Dystrophy (SMD).

ACT recently announced Data and Safety Monitoring Board (DSMB) approval to move forward with enrollment and treatment of additional patients with SMD in its U.S. SMD trial, and to treat the final two patients to round out the initial dosing arm in its European trial. All three of the companys ongoing clinical trials use human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells.

About SMD, Dry AMD and Degenerative Diseases of the Retina

Stargardts Macular Dystrophy (SMD) is one of the most common forms of macular degeneration in the world. SMD causes progressive vision loss, usually starting in children between 10 to 20 years of age. Eventually, blindness results from photoreceptor loss associated with degeneration in the pigmented layer of the retina, called the retinal pigment epithelium or RPE cell layer.

Degenerative diseases of the retina are among the most common causes of untreatable blindness in the world. As many as thirty million people in the United States and Europe suffer from macular degeneration, which represents a $25-30 billion worldwide market that has yet to be effectively addressed. Approximately 10% of people ages 66 to 74 will have symptoms of macular degeneration, the vast majority the dry form of AMD which is currently untreatable. The prevalence increases to 30% in patients 75 to 85 years of age.

About Advanced Cell Technology, Inc.

Advanced Cell Technology, Inc., is a biotechnology company applying cellular technology in the field of regenerative medicine. For more information, visit http://www.advancedcell.com.

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Advanced Cell Technology to Present at World Stem Cells & Regenerative Medicine Congress in London

Newswise May 17, 2012 - Oakland, Calif. Scientists at Childrens Hospital Oakland Research Institute (CHORI) led by Vladimir Serikov, MD, PhD, and Frans Kuypers, PhD, report in the current Epub issue of Stem Cells Translational Medicine (1) that placental stem cells with important therapeutic properties can be harvested in large quantities from the fetal side of human term placentas (called the chorion). The chorion is a part of the afterbirth and is normally discarded after delivery, but it contains stem cells of fetal origin that appear to be pluripotent -- i.e., they can differentiate into different types of human cells, such as lung, liver, or brain cells. Since these functional placental stem cells can be isolated from either fresh or frozen term human placentas, this implies that if each individuals placenta is stored at birth instead of thrown away, these cells can be harvested in the future if therapeutic need arises. This potential represents a major breakthrough in the stem cell field.

In previous work, Drs. Serikov and Kuypers reported a novel technology to harvest blood-forming stem cells from the placenta to augment cord blood cells (2). These cells are siblings of the cord blood derived stem cells. Cord blood stem cells, unlike embryonic stem cells, have been used for many hundreds of successful bone marrow transplants. These transplants are mainly performed in children, as the amount of cells that can be harvested from cord blood is usually not sufficient for a successful transplant in adults. Adding placental-derived stem cells to the cord blood stem cells could make successful adult bone marrow transplants routinely possible.

The current report (1) demonstrates that placental stem cells have much broader therapeutic potential than bone-marrow transplants, because they are pluripotent i.e. able to differentiate into many different cell types -- and they also generate growth factors that help in tissue repair. These cells are shown to integrate into different tissues when transplanted into mice, but like cord blood stem cells, and in contrast to embryonic pluripotent stem cells, they do not form tumor-like structures in mice.

Placental-derived stem cells are often viewed as adult stem cells in contrast to embryonic stem cells, which are the dominant focus in the stem cell research field. However, this report shows that these fetal stem cells can be harvested in large numbers, and without the ethical concerns attached to the use of embryonic stem cells. These stem cells may thus be a more practical source for regenerative medicine, particularly since, if placentas are routinely saved instead of thrown away, each individual will be able to draw on their own fetal stem cells if future therapeutic needs arise.

Placental stem cells are only 9 months old, and in contrast to adult stem cells, do not need to be reprogrammed to become pluripotent. Placental-derived stem cells have characteristics of young and vigorous cells, including young mitochondria. Future research will be aimed to bring this to the clinic and to test their efficacy in translational therapeutic applications.

Childrens Hospital Oakland Research Institute (CHORI), is known internationally for state-of-the-art basic and clinical research and translating it into interventions for treating and preventing human diseases. CHORI has 300 members of its investigative staff, a budget of about $50 million, and is ranked among the nations top 10 research centers in National Institutes of Health funding to childrens hospitals. For more information, go to http://www.childrenshospitaloakland.org and http://www.chori.org.

References 1. Nazarov I, Lee J, Soupene E, Etemad S, Knapik D, Green W, Bashkirova E, Fang X, Matthay MA, Kuypers FA, Serikov VB. Multipotent Stromal Stem Cells from Human Placenta Demonstrate High Therapeutic Potential. Stem Cells Translational Medicine :2012;2011:2000 2000 http://www.StemCellsTM.com : Link to Abstract: http://stemcellstm.alphamedpress.org/content/early/2012/05/08/sctm.2011-0021.abstract, 2012. To appear in the June 2012 print issue. 2. Serikov V, Hounshell C, Larkin S, Green W, Ikeda H, Walters MC, Kuypers FA. Human Term Placenta as a Source of Hematopoietic Cells. Exp Biol Med (Maywood) 234:813-823, 2009.

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Multipotent Stromal Stem Cells from Normally Discarded Human Placental Tissue Demonstrate High Therapeutic Potential

17 May 2012 Last updated at 21:37 ET

A father who lost his son to leukaemia is calling for secondary schools and colleges to include one lesson on how to donate stem cells, blood and organs.

Keith Sudbury wants to raise awareness by making donation part of the curriculum for students aged 16 and over.

His son Adrian received a stem cell transplant which gave him an extra year of life, but died aged 27.

Blood cancer charity Anthony Nolan is supporting the idea of 'Adrian's Law'.

Adrian spent the last two years of his life campaigning for better education about stem cell donation.

He took a petition to Downing Street and met the then Prime Minister Gordon Brown to talk about the campaign to get more young people to register as donors.

With Adrian's Law, his parents Kay and Keith want the message to reach more young people and they hope that there will be a Private Member's Bill in the Commons to highlight its importance.

We can grow the first generation of potential lifesavers.

"We urgently need more people willing to donate blood and stem cells," Keith Sudbury said.

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Father wants 'donation' lessons

SALT LAKE CITY -- Utahs scandal-plagued, state-owned liquor business will have a new management scheme. After weeks of back-room negotiations, legislators and the governor have found a compromise.

Right now, in Utah the governor is mostly excluded from liquor policy. He will get a lot more power in liquor. But he will have to share power with the independent liquor commission. All of this change is in the hope of avoiding new scandals.

We have reached a compromise on the governance for alcohol policy for the state of Utah, said Sen. John Valentine. Governor Gary Herbert wanted the liquor commission to disappear. He wanted the governor to run liquor, as he runs other state departments. Prior to 1977, we had it all under the executive branch, said Valentine. But Valentine studied history. When liquor was under the governor, distilleries donated booze to the governor's fundraising gala. And in 1976, under Governor Calvin L. Rampton, there was a scandal. We ended up with five indictments. We ended up with a governor who ended up with 30 cases of booze up at the mansion that we couldnt account for, said Valentine. So the legislature created the liquor commission. But now under the commission, former Liquor Chief Dennis Cullen is accused of insider dealing with a firm owned by his son. In running the state liquor business, Utah moves from scandal to scandal. Utah has tried the governor running liquor, and tried the commission running liquor, and after this latest scandal, Utah will try a combination of the governor and the commission.

(Copyright 2012 Sinclair Broadcast Group) Legislators, Governor Find Comprise For Liquor Business Management

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Stem Cells Used To Repair Damaged Teeth