SEOUL, South Korea, Sept. 26, 2012 /PRNewswire/ --In the first study of its kind, researchers at Korea's leading university and the RNL Bio Stem Cell Technology Institute announced this week the results of a study that suggests an astounding possibility: adult stem cells may not only have a positive effect on those suffering from Alzheimer's disease, theycanprevent the disease.Using fat-derived adultstem cells from humans [scientific term:adMSCs, orhuman, adipose-derived mesenchymal stem cells], researchers were able to cause Alzheimer's disease brains in animal models to regenerate. The researchers, for the first time in history, used stem cells toidentify the mechanism that is key to treatment of Alzheimer's disease, and demonstrated how to achieve efficacy as well as prevention of the symptoms of Alzheimer's with adult stem cells, a "holy grail" of biomedical scientists for decades.

Alzheimer's disease, the most common form of dementia (loss of brain function), is the 6th leading cause of death, and affects 1 in 8 people -- more than breast cancer. As of 2010, there were 35.6 million people with Alzheimer's disease in the world, but this number is expected to double every 20 years. It is estimated that the total cost of Alzheimer's is US $604 billion worldwide, with 70% of this cost in the US and Europe. To put that in perspective, Alzheimer's care costs more than the revenues of Wal-Mart (US$414 billion) and Exxon Mobil (US$311 billion), according to the British World Alzheimer's Report of ADI. The cost of Alzheimer's is at the top of health economists' list of the disorders of aging that could topple nations' entire economies, and that regularly ruin not only the lives of patients but of their relatives.

According to the results of this first major study, Alzheimer's may soon be a preventable disease, or even a thing of the past. Equally important, the safety human administration of the kind of adult stem cells used in this experiment has been established in multiple articles and government-approved clinical trials.

THE RESEARCH:

The study was jointly led by Seoul National University Professor Yoo-Hun Suh and RNL Bio Stem Cell Technology Institute (SCTI) director Dr. Jeong-Chan Ra.

The researchers and their teams injected stem cells into mice genetically designed to have the core symptoms and physiology of Alzheimer's disease. They were able to identify that these human stem cells, derived from adipose tissue, behave in a very special way when injected into the tail vein of mice subjects. The cells migrated through the blood brain barrier, thought by many to be impossible for adult stem cells to cross, and went into the brain. In fact,fluorescent labeled cells were monitored for distribution in subjects and the team identified that the infused cells migrated throughout the bodiesincluding brainexcept the olfactory organ, and therefore confirmed that IV infused stem cell can reach to the brain across the blood brain barrier.

The team infused human adipose stem cells intravenously in Alzheimer model mice multiple times two weeks apart from three month to 10 month.Once there, the mice who received cells improved in every relevant way: ability to learn, ability to remember, and neuropathological signs. More important, for the first time ever, Alzheimer model mice showed the mediation of IL-10, which is known for anti-inflammation and neurological protection.

The team also found that stem cell restored special learning ability from Alzheimer model subjects with great reduction of neuropathy lesions.This was found using tests used for Alzheimer's disease: behavioral assessment. In assessment it was found, amazingly, that stem cells' therapeutic effect on Alzheimer's disease was tremendous. This was also found in pathological analysis. The key though was prevention: the scientists showed that stem cells, when infused into Alzheimer's mice, decreased beta amyloid and APP-CT, known to cause brain cell destruction, leading to dementia and Alzheimer's disease. In the lab it was clear that stem cells increased neprilysin, which hydrolyzes toxic proteins. No other compound or treatment has ever suggested so strongly the potential to prevent, as well as stop, this epidemic of incurable dementia sweeping across suffering patients and their families.

Stopping Alzheimer's disease, let alone preventing it, is the focus of thousands of researchers worldwide. Speaking of their breakthrough discovery,Professor Yoo-Hun Suh, who led the study, said, "It is a ground breaking discovery that such a simple method as IV injection of the safest autologous adipose stem cells, without causing any immune rejection, or any ethical issues, opened a new door to conquering Alzheimer's disease, one of the most horrible, expensive and incurablediseases of our time." Joining him, leader of the RNL Bio Stem Cell Technology InstituteDr. Jeong-Chan Ra said, "It has never been more clear that it is an ethical imperative for governments to provide patients with incurable diseases with their right to participate not only in studies like this but in therapies with such obvious potential, once they have been tested as many times for safety as has our technology." Both scientists stressed that the real breakthrough in their complex research is the prevention of the onset of symptoms.

Specifically, stem cells grafted in the brain, in another part of the study, were identified to induce cell division and neuro differentiation of endogenous neuro progenitor cells around the hippocampus and its surrounding cells and increase in great deal the stability of dendrites and synapses. Stem cell also contributed various anti-inflammatory and neuro growth factors, especially increased the expression of IL-10. This again suppressed apoptosis of brain neurons, the prevention effect against Alzheimer's disease.

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Study Shows Stem Cells May Prevent And Cure Alzheimer's

A 10-year-old boy has been infused with stem cells harvested from the bone marrow of his brother to treat him for thalassaemia a disorder caused by destruction of red blood cells. Called allogeneic transplantation of stem cells, this was done at Kovai Medical Center and Hospital.

D. Dhanush may not have to undergo expensive and excruciating blood transfusion anymore if his body accepts the donor cells. But his condition will have to be evaluated very minutely for the next two years to confirm that the cells donated by his brother have been received well and adapted him.

Presenting the boy before media persons, Clinical Haematologist and Head of the Bone Marrow Transplant Unit T. Rajasekar explained that transplantation was of two types autologous and allogeneic.

The autologous procedure involves harvesting of stem cells from the patients themselves (those suffering from thalassaemia or leukaemia). The extracted cells are frozen and stored for high dose treatment.

After being treated, these are infused into the patient through a vein. This procedure was done for one person suffering from myeloma (cancer of plasma cells or white blood cells that produce anti-bodies that help fight infections/diseases) and another with a relapsed lymphoma (cancer of the lymphocytes cells that are part of immune system).

Under the allogeneic procedure, matching stem cells from a donor are used. Mostly, these cells are from siblings or a close relative as they need to pass the human leukocyte antigen (HLA) matching test. HLA matching is required, or the cells will be rejected by the recipient. Ideally, it is sibling whose cells will match because he or she will have the HLA from both parents. It is the combination of HLAs from both parents that are found in the children.

The cells can be harvested from the marrow or from the blood. In the case presented on Tuesday, Dr. Rajasekar said the cells were brought out of the bone marrow in Dhanushs brother and into his blood, from where these were harvested.

Chairman of the hospital Nalla G. Palaniswami said the tough procedure was performed by the new Comprehensive Cancer Centre, which was gradually bringing in specialists of all sub-specialities of cancer care. Only then can this be called a comprehensive centre, he said.

The hospital would form a KMCH Foundation, which would use funds from donors to treat poor children suffering from cancer and some other disorders that required expensive treatment.

The stem cell transplantation that Dhanush, the son of a police head constable, underwent cost Rs.12 lakh. Of this, Rs.9 lakh was provided by a donor, Dr. Palaniswami said. Dean of the hospital V. Kumaran and Head of Department of Interventional Radiology Mathew Cherian spoke on how the cancer centre was established and how developments were being made.

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Stem cell transplantation for boy with thalassaemia

ScienceDaily (Sep. 25, 2012) The process researchers use to generate induced pluripotent stem cells (iPSCs) -- a special type of stem cell that can be made in the lab from any type of adult cell -- is time consuming and inefficient. To speed things up, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) turned to kinase inhibitors. These chemical compounds block the activity of kinases, enzymes responsible for many aspects of cellular communication, survival, and growth.

As they outline in a paper published September 25 in Nature Communications, the team found several kinase inhibitors that, when added to starter cells, help generate many more iPSCs than the standard method. This new capability will likely speed up research in many fields, better enabling scientists around the world to study human disease and develop new treatments.

"Generating iPSCs depends on the regulation of communication networks within cells," explained Tariq Rana, Ph.D., program director in Sanford-Burnham's Sanford Children's Health Research Center and senior author of the study. "So, when you start manipulating which genes are turned on or off in cells to create pluripotent stem cells, you are probably activating a large number of kinases. Since many of these active kinases are likely inhibiting the conversion to iPSCs, it made sense to us that adding inhibitors might lower the barrier."

According to Tony Hunter, Ph.D., professor in the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies and director of the Salk Institute Cancer Center, "The identification of small molecules that improve the efficiency of generating iPSCs is an important step forward in being able to use these cells therapeutically. Tariq Rana's exciting new work has uncovered a class of protein kinase inhibitors that override the normal barriers to efficient iPSC formation, and these inhibitors should prove useful in generating iPSCs from new sources for experimental and ultimately therapeutic purposes." Hunter, a kinase expert, was not involved in this study.

The promise of iPSCs

At the moment, the only treatment option available to many heart failure patients is a heart transplant. Looking for a better alternative, many researchers are coaxing stem cells into new heart muscle. In Alzheimer's disease, researchers are also interested in stem cells, using them to reproduce a person's own malfunctioning brain cells in a dish, where they can be used to test therapeutic drugs. But where do these stem cells come from? Since the advent of iPSC technology, the answer in many cases is the lab. Like their embryonic cousins, iPSCs can be used to generate just about any cell type -- heart, brain, or muscle, to name a few -- that can be used to test new therapies or potentially to replace diseased or damaged tissue.

It sounds simple enough: you start with any type of differentiated cell, such as skin cells, add four molecules that reprogram the cells' genomes, and then try to catch those that successfully revert to unspecialized iPSCs. But the process takes a long time and isn't very efficient -- you can start with thousands of skin cells and end up with just a few iPSCs.

Inhibiting kinases to make more iPSCs

Zhonghan Li, a graduate student in Rana's laboratory, took on the task of finding kinase inhibitors that might speed up the iPSC-generating process. Scientists in the Conrad Prebys Center for Chemical Genomics, Sanford-Burnham's drug discovery facility, provided Li with a collection of more than 240 chemical compounds that inhibit kinases. Li painstakingly added them one-by-one to his cells and waited to see what happened. Several kinase inhibitors produced many more iPSCs than the untreated cells -- in some cases too many iPSCs for the tiny dish housing them. The most potent inhibitors targeted three kinases in particular: AurkA, P38, and IP3K.

Working with the staff in Sanford-Burnham's genomics, bioinformatics, animal modeling, and histology core facilities -- valuable resources and expertise available to all Sanford-Burnham scientists and the scientific community at large -- Rana and Li further confirmed the specificity of their findings and even nailed down the mechanism behind one inhibitor's beneficial actions.

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Making it easier to make stem cells: Kinase inhibitors lower barrier to producing stem cells in lab

Public release date: 25-Sep-2012 [ | E-mail | Share ]

Contact: David Eve cellmedicinect@gmail.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Tampa, Fla. (Sep. 25, 2012) In a study to investigate how transplanted islet cells can differentiate and mature into insulin-producing pancreatic cells, a team of Japanese researchers found that using a specific set of transcription factors (proteins that bind to specific DNA sequences) could be transduced into mouse pancreatic stem cells (mPSCs) using Sendai virus (SeV), a mouse influenza virus, as a carrier, or vector. The study is published in a recent issue of Cell Medicine [3(1)], now freely available on-line at: http://www.ingentaconnect.com/content/cog/cm.

"Diabetes is one of the most serious and prevalent metabolic diseases," said study co-author Dr. Hiroshi Yukawa, Department of Advanced Medicine in Biotechnology and Robotics, Nagoya University Graduate School of Medicine. "Islet cell transplantation has proven effective, however this strategy requires sufficient organ donors."

Given the shortage of donors, the researchers investigated factors that could impact on the expansion and differentiation of pancreatic stem cells (PSCs) into insulin-producing cells using combinations of varieties of transcription factors and the SeV mouse virus to carry the cells, thus increasing the number of functional islet cells available for transplantation.

SeV vectors, said the researchers, are superior to conventional virus vectors because "they do not go through a DNA phase" and can introduce foreign genes without toxicity into a variety of cell types.

The combination of transcription factors that produced the greatest impact on the differentiation of PSCs into insulin cells was Pdx-1 (Pancreatic and duodenal homeobox 1), NeuroD (neurogenic differentiation) and MafA (musculoaponeurotic fibrosarcoma oncogene A). "Our data suggest that the transduction of transcription factors using SeV vectors facilitates mPSCs differentiation into insulin producing cells and showed the possibility of regenerating B-cells by using transduced PSCs," concluded the researchers.

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This research was among those studies presented at the 37th Annual Meeting of the Japan Society for Organ Preservation and Medical Biology (JSOPMB). Sixteen studies were published in this special issue of CELL MEDICINE. The theme of the issue is "Organ/Cell Transplantation and Regenerative Medicine."

Citation. Yukawa, H.; Noguchi, H.; Oishi, K.; Miyamoto, Y.; Inoue, M.; Hasegawa, M.; Hayashi, S. Differentiation of Mouse Pancreatic Stem Cells into Insulin-Producing Cells by Recombinant Sendai Virus-Mediated Gene Transfer Technology Cell Med. 3(1):51-61; 2012.

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Mouse pancreatic stem cells successfully differentiate into insulin producing cells

Public release date: 25-Sep-2012 [ | E-mail | Share ]

Contact: David Eve cellmedicinect@gmail.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Tampa, Fla. (Sep. 25, 2012) In a study to determine the best cryopreservation (freezing) solution to maintain induced pluripotent stem (iPS) cells, a team of researchers from Japan compared 12 kinds of commercially prepared and readily available cryopreservation solutions and found that "Cell Banker 3" out-performed the other 11 solutions by allowing iPS cells to be preserved for a year at degrees C in an undifferentiated state.

The study is published in a recent special issue of Cell Medicine [3(1)], now freely available on-line at: http://www.ingentaconnect.com/content/cog/cm.

"iPS cells are a promising alternative to embryonic stem cells and can be used in place of bone marrow cells, stromal cells and adipose tissue-derived stem cells," said study co-author Hirofumi Noguchi, MD, PhD, Department of Gastroenterological Surgery, Transplant and Surgical Oncology at the Okayama University Graduate School of Medicine. "However, the viability of human iPS cells, like embryonic stem cells, decreases significantly during cryopreservation. A wide variety of cryopreservation solutions have been used, however many are toxic or ineffective for use in extended cryopreservation."

The researchers concluded that Cell Banker 3 showed the highest cell viability and proliferation of all the solutions examined and can be widely used as it does not require any special skills for use.

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This research was among those studies presented at the 37th Annual Meeting of the Japan Society for Organ Preservation and Medical Biology (JSOPMB). Sixteen studies were published in this special issue of CELL MEDICINE. The theme of the issue is "Organ/Cell Transplantation and Regenerative Medicine."

Citation: Miyamoto, Y.; Noguchi, H.; Yukawa, H.; Oishi, K.; Matsushita, K.; Iwata, H.; Hayashi, S. Cryopreservation of Induced Pluripotent Stem Cells. Cell Med. 3(1):89-95; 2012.

Contact: Dr. Hirofumi Noguchi, Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Okayama 700-8558 Japan Tel + 81-86-235-7257; Fax + 81-86-221-8775 Noguchih2006@yahoo.co.jp / noguch-h@cc.okayama-u.ac.jp

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Cryopreservation of induced pluripotent stem cells improved the most by one product

ScienceDaily (Sep. 25, 2012) A new video protocol in Journal of Visualized Experiments (JoVE) details an assay to identify brain tumor initiating stem cells from primary brain tumors. Through flow cytometry, scientists separate stem cells from the rest of the tumor, allowing quick and efficient analysis of target cells. This approach has been effectively used to identify similar stem cells in leukemia patients.

"Overall, these tumors are extremely rare, with only around one in 100,000 people being diagnosed with a primary brain cancer," Dr. Sheila Singh, co-author and neurosurgeon from McMaster University, explains. "However, these tumors are the second most common malignancy in the pediatric population, and are behind only leukemia as the cancer with the highest mortality rate."

This publication is significant because it allows scientists to identify, purify, and study brain tumor initiating cells rapidly and without sample loss. Because these stem cells allow scientists to grow films in a petri dish, they serve as an effective model of a tumor expanding in the brain of a patient. Though not all tumors are actively driven by a stem cell, they do drive the most aggressively expanding tumors that lead to a negative prognosis. Typically, the median survival for patients with these types of tumors is fifteen-months, and they are almost uniformly fatal. Currently there is no prospect for a cure.

"Since 2003, we've been perfecting the technique to isolate stem cells from brain tumors," Dr. Singh explains. Stem cells have three key properties: self-renewal, multilineage differentiation, and longevity. Studying stem cells allow scientists to develop therapies that not only target the progenitor cells, but also many of the daughter cells. This is crucial because stem cells are often hard to eradicate without adverse effects to the rest of the body. Once daughter cells are identified, this procedure can be used to target and isolate these cells as well. Singh continues, "By describing the entire hierarchy of tumor progenitor cells, we can describe, characterize and target any point in the lineage. These techniques are going to help us characterize and isolate these cells to learn more about their molecular underpinnings and how to target them."

Given the small amount of tissue available to scientists like Dr. Singh, analytic procedures must be incredibly efficient and precise so as not to waste the precious material. Since Dr. Singh first identified brain tumor initiating cells, she has "recognized the difficulties in working with these tissues." Singh's lab "has focused on optimizing these procedures, which are limited by small cell numbers, to increase the data output." As such, JoVE's unique video-text hybrid serves as an effective means to transmit the procedures to Dr. Singh's colleagues and other cancer researchers. JoVE is the world's first peer-reviewed science video journal indexed in PubMed and MEDLINE.

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Isolating stem cells from brain tumors