Category Archives: New York Stem Cells

NEW YORK, March 5, 2015 /PRNewswire-USNewswire/ -- New York Blood Center (NYBC) recently launched a new mobile app providing a convenient, user friendly platform for blood donors to find donation locations, make and manage appointments, view donation history and donor profiles, and access the full NYBC website to manage Donor Advantage accounts, redeem points, and much more.

"With the launch of our new mobile app, we continue efforts to enhance the donation experience for the many blood donors who make such a profound difference in the lives of patients in need," said NYBC Executive Director of Donor Marketing Harvey Schaffler. "NYBC's app provides donors with the quick and easy convenience of mobile access to the most up-to-date donation information on the go and at their fingertips."

The app is available free of charge in the App Store for iPhone and Android. Search "NYBC" to download the app today.

To schedule a blood donation, visit http://www.nybloodcenter.org or call 1-800-933-2566 (BLOOD).

Forinformation about the Donor Advantage Program, please visit http://www.mydonoradvantage.com.

About New York Blood CenterNow celebrating its 50th anniversary, New York Blood Center (NYBC) is one of the largest independent, community-based blood centers in the country. Each year, NYBC provides approximately one million blood products to nearly 200 hospitals in the Northeast. NYBC also provides a wide array of transfusion-related medical services. NYBC is also home to the world's largest public cord blood bank, which provides stem cells for transplant in many countries, and a renowned research institute, which, among other milestones, developed the Hepatitis B vaccine and innovative blood purification technology. Please visit us on Facebook at http://www.facebook.com/newyorkbloodcenter.

Follow us on Twitter: @NY_BloodCenter. http://www.nybloodcenter.org

CONTACT: Harvey Schaffler, 516-478-5021

SOURCE New York Blood Center

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New York Blood Center's New Mobile App Helps Save Lives On the Go

Study led by NYU Langone Medical Center adds to groundwork for cell-based treatment of disease

New York, NY -- Scientists at NYU Langone Medical Center and New York University have demonstrated that a specialized DNA-binding protein called CTCF is essential for the precise expression of genes that control the body plan of a developing embryo.

The findings, to publish online February 27 in Science, focus on mouse brain cells that work to manage an animal's movements. The results add important details to how so-called Hox genes help cells keep their positions straight and in the right positions back to front.

Hox genes are arranged in particular clusters on an animal genome and only a subset of Hox genes are active in a given cell. Maintaining a precise "memory" from mother cell to daughter cell of active and inactive Hox genes is fundamental to establishing a normal body plan, the researchers report, and failure of that system produces a body part in the wrong anatomical position.

"Previous research has shown that CTCF acts as a key insulating barrier to prevent mistakes in cells as they multiply and differentiate," says Varun Narendra, the study's lead author, and a fifth-year graduate PhD student in developmental biology at NYU Langone and the Howard Hughes Medical Institute. "Now we have shown that correct positioning also depends on CTCF."

"The findings provide new insight into how cells faithfully transmit this organizational information as embryos develop, and into what goes wrong when cellular development goes awry, thereby giving rise to abnormal cell development and diseases such as cancer," says senior study investigator Danny Reinberg, PhD, professor of biochemistry and molecular pharmacology at NYU Langone and a Howard Hughes Medical Institute investigator. "Information from this study could help lay the groundwork for therapies that address developmental missteps tied to Hox genes and their regulators."

CTCF is a so-called DNA-binding protein, which marks regions of DNA in animal genomes that serve as "insulators" or partitioning boundaries as cells package their DNA. What the researchers discovered is that CTCF binding ensures that segments of the genome that are packaged to be active do not interfere with neighboring segments that should not be active in the daughter cells they generate.

Using mouse embryonic stem cells that generate motor neurons as a model, the researchers found that CTCF isolates Hox genes from harmful activation. "We found that the activity of CTCF is to divide the Hox cluster into segments, allowing the cluster to fold into strict domains that are either active or inactive on either side of CTCF," Narendra adds.

To demonstrate that CTCF binding is necessary for correct Hox gene activation, the researchers removed the sites on the genome where CTCF would normally bind and showed that without that CTCF binding, the Hox cluster would not fold properly. As a result, motor neurons activated the wrong set of Hox genes.

"By altering the folding pattern of the Hox cluster, we altered the motor neurons' understanding of their anatomical position," says Esteban Mazzoni, PhD, a study co-investigator and assistant professor of biology and New York University. "In doing so, we also altered their ability to send nerve signals to the appropriate muscle targets."

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Study affirms role of specialized protein in assuring normal cell development

Redwood City, CA (PRWEB) February 23, 2015

The iovera system, cleared by the FDA to treat peripheral nerve pain, utilizes its patented Focused Cold TherapyTM delivery system to direct a controlled cold dosage via closed-end probes to specific nerves for precise, predictable, drug-free pain relief.

The iovera treatment provides my knee pain patients with a very effective, natural option that provides relief precisely at their point of pain allowing them, in many cases, to avoid or reduce their need for systemic painkillers, said Sudhir Diwan, M.D., Manhattan Spine and Pain. My patients are excited to have a minimally-invasive, drug-free treatment that enables them to walk out of my office pain-free and stay that way for up to 3 months.

Patients are relieved when they realize that there is a minimally-invasive, non-systemic option that can give them instant knee pain relief, said Halland Chen, M.D., of Dr. Halland Medical. Theres something familiar and comforting to patients about using the simple power of cold to eliminate pain, and with iovera we can now use cold in a very high-tech, precise way to block specific nerve signals temporarily.

Frequent knee pain limits function and mobility, and impairs quality of life for approximately 25% of adults.1 Peripheral nerves treated with the iovera system are temporarily stopped from signalling for a period of time, followed by a restoration of function - results may vary per patient*. Because peripheral nerve function is disrupted rather than destroyed, the results are safe, effective and temporary.

We are so pleased that these pain specialists have seen the unique value of the Focused Cold Therapy delivery system for patients with knee pain, said Jeff Gold, myoscience CEO. The iovera treatment allows physicians to target a patients pain directly at the source by treating the specific peripheral nerves involved with a natural, safe dose of cold that temporarily stops the nerves from signalling and delivers immediate pain relief.

The iovera system delivers liquid nitrous oxide from a convenient and powerful handheld device to the closed-end probes of the Smart Tip during treatment. While this highly pressurized liquid travels from the handpiece to the Smart Tip, it undergoes a phase change becoming very cold, drawing in heat energy from the surrounding tissue and forming a precise zone of cold at thetargeted nerve. The gaseous nitrous oxide returns into the handpiece, leaving nothing behind in the body. This precise cold treatment causes a reversible nerve block based on a process called Wallerian degeneration. Pain is relieved in sensory nerves, which send messages to the central nervous system. The nerve re-innervates 1-2 mm per day, which gives a predictable restoration of nerve function.

About iovera The Food and Drug Administration (FDA) cleared the iovera system for use in peripheral nerves in January 2013. iovera is being used most frequently for knee pain but can be used to treat pain in any peripheral nerve. The iovera system is specifically cleared to destroy tissue during surgical procedures by applying cold temperature. It can also be used to produce lesions in peripheral nervous tissue by the application of cold to the selected site for the blocking of pain. The iovera system is not indicated for treatment of central nervous system tissue.

About the Manhattan Spine and Pain Medicine Manhattan Spine and Pain Medicine physicians listen and treat pain without surgery. Their passion is improving patients quality of life. Pain management is the medical specialty focused solely on treating patients in acute and chronic pain. The practices goal is to restore function and improve the quality of life for those in pain. The board-certified physicians at Manhattan Spine and Pain listen diagnose and treat pain from head to toe using a range of non-surgical treatment options. For more information about the Manhattan Spine and Pain Medicine please visit: https://treatingpain.com/mspm. Patients interested in iovera treatment at Manhattan Spine and Pain can call 877-463-7264.

About Dr. Halland Medical Dr. Halland Chen specializes in pain management. His practice is focused on non-surgical knee and spine treatments, with a special emphasis on regenerative medicine and organic options through the use of PRP, Stem Cells and natural supplements. Dr. Halland Medical applies its unique techniques for patients to address sports injuries, pain management conditions, and cosmetic anti-aging. Dr. Halland specializes in injection therapy and minimally invasive techniques. For more information about Dr. Halland Medical please visit: http://drhalland.com. Patients interested in iovera treatment at Dr. Halland Medical can call: 212-464-8772.

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New York City Pain Specialists Introduce New Treatment for Knee Pain; First Physicians in Northeast to Offer iovera ...

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Newswise (NEW YORK February 19) Renowned neuropsychiatric researcher Alison Goate, PhD, has joined the Mount Sinai Health System as the founding Director of the Ronald M. Loeb Center for Alzheimers Disease. Established by a recent $15 million gift from Daniel S. Loeb, CEO and Founder of Third Point, LLC and his wife, Margaret Munzer Loeb, in memory of Daniels father, Ronald M. Loeb, the center will provide a focus for a network of research programs closely tied to research and clinical initiatives across the Health System.

As a molecular geneticist, Dr. Goate has established an international reputation for her research to elucidate the genetic, molecular and cellular basis of Alzheimers disease (AD) and related neurodegenerative disorders.

Alison brings to Mount Sinai a research history distinguished by its translational and interdisciplinary focus, integrating molecular and genetic studies, says Eric Nestler, MD, PhD, Nash Family Professor and Chair of the Department of Neuroscience and Director of the Friedman Brain Institute in the Icahn School of Medicine at Mount Sinai. Her research team will help Mount Sinai play a global leading role in finding new and better treatments for Alzheimers disease and other disorders.

She has identified key gene mutations linked to the heritable risk for Alzheimers disease, including her finding that a rare mutation of the PLD3 gene doubles the risk of developing late onset AD. Prior to joining Mount Sinai, Dr. Goate led a team of researchers at Washington University, St. Louis, that performed the largest ever genome-wide association study of protein markers found in cerebrospinal fluid, resulting in the discovery of three genetic variants that may come with an increased risk of developing AD.

Alison Goate is truly one of the chief architects of the genomics revolution happening in Alzheimers disease research, says Mount Sinai President and Chief Executive Officer Kenneth L. Davis, MD. Under her leadership, we will bring together Mount Sinais core competencies in genomics, bioinformatics, imaging and clinical trials to vigorously pursue major breakthroughs for a disease that touches so many lives.

As Director of the Ronald M. Loeb Center for Alzheimers Disease at Mount Sinai, Dr. Goate will recruit new talent in areas such as induced pluripotent stem cells or IPSCs. In this line of research, researchers take a patients skin cells, for instance and coax them back along the differentiation pathway to become stem cells. These induced cells can then be differentiated into any kind of cell in the body, including neurons. Because the resulting cells are genetically identical to those found in the donor, researchers can use them to model disease and safely investigate the efficacy of new drug treatments at the cellular level in a way not previously possible.

Alison is a transformative recruit to Mount Sinai, says Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine at Mount Sinai and President for Academic Affairs for the Mount Sinai Health System. Our mission is nothing less than discovering the causes and better treatments for Alzheimers disease and related conditions. Through Dr. Goates leadership of the Ronald M. Loeb Center for Alzheimers Disease, Mount Sinai is one of the nations few centers capable of achieving these ambitious goals.

Dr. Goate will also establish ties between the Center and the many basic and clinical researchers across the Mount Sinai Health System focused on neurodegenerative disorders. In particular, she will work closely with: the Alzheimers Disease Research Center, funded by the National Health Institutes National Institute on Aging and directed by Mary Sano, PhD, one of the nations leaders in clinical trials of Alzheimers disease; the Center for Cognitive Health, directed by Sam Gandy, MD, PhD, an expert on the amyloid plaque protein linked to Alzheimers disease; and faculty of the Icahn Institute for Genomics & Multiscale Biology, directed by Eric Schadt, PhD, who have an NIA-funded program that applies multi-scale biology to Alzheimers disease. In addition, Dr. Goate has an established research program on the genetics of alcoholism and so will broaden Mount Sinais portfolio in this disorder as well.

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Mount Sinai Health System Names Director of Newly Established Ronald M. Loeb Center for Alzheimer's Disease

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Newswise (New York January 30, 2015) Two existing cancer drugs turn on a gene that tells tumor cells to remain inactive, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai and published today in Nature Communications.

Researchers discovered that the gene NR2F1, when switched on, programs tumor cells to stay dormant. When the gene is switched off, tumor cells divide and multiply as part of abnormal growth, potentially allowing dormant cells to grow into tumors throughout the body (metastasis). Combining the anticancer drugs azacytidine and retinoic acid significantly increased the amount of active NR2F1 in tumor cells. These patterns were found in mouse models of several cancers, and confirmed in prostate cancer cells from human patients.

Results suggest that NR2F1 is a master regulator of tumor cell growth, influencing several genes that determine whether cells remain inactive, or quiescent in medical terms. According to the study, NR2F1 exerts control over long lasting programs in stem cells in the human embryo, where it directs cells to stop growing and become specialized cells (neurons) for life. This function suggests that NR2F1 may exert a long-lasting effect on tumor cells, keeping them dormant after they have broken off from an original tumor.

Our results explain why some tumor cells scattered through the body are committed to remaining harmless for years, while others cause active disease, said Julio A. Aguirre-Ghiso, PhD, Professor of Medicine, Hematology and Medical Oncology, and Otolaryngology at the Icahn School of Medicine. In finding this master switch we found a way to analyze tumor cells before treatment to determine the risk of a cancer recurrence or metastasis.

Azacytidine and retinoic acid, the latter a form of vitamin A, prevented tumor cells from rapidly multiplying, restored normal cell function, and activated several tumor suppressor genes that are often turned off in tumors, said study co-leader Maria Soledad Sosa, PhD, a postdoctoral fellow in Hematology at the Icahn School of Medicine. We now have strong evidence that combining these well-known drugs may have a profound, long-lasting therapeutic effect.

The current study builds on the research teams earlier finding that lowering amounts of tumor suppressor genes TGF2 and p38 awakened dormant tumor cells, fueling metastatic tumor growth. Azacytidine and retinoic acid restored TGF2 expression and p38 activation to drive tumor cell dormancy.

This study was supported by grants from the Samuel Waxman Cancer Research Foundation, National Cancer Institute, National Institute of Environmental Health Sciences, New York State Stem Cell Science program, JJR Foundation and Hirschl/Weill-Caulier Trust, Department of Defense and Janssen Research and Development LLC.

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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Master Switch Found to Stop Tumor Cell Growth by Inducing Dormancy

When Professor Michael Lisanti chatted to his eight-year-old about his job finding a cure for cancer - he had no idea she would provide just the inspiration he was looking for.

The family were having dinner when Michael asked schoolgirl Camilla how she would go about treating cancer.

Her answer was simple - but proved to be a brainwave.

Camilla said people who are ill should take antibiotics.

And after dad Prof Lisanti - and mum Dr Federica Sotgia - dug a little deeper, it turned out she could be spot on.

Prof Lisanti, director of the Breakthrough Breast Cancer Unit at the university, led the research after being inspired by his daughter to look at the effects of the drugs on the mitochondria of cancer stem cells.

He found that drugs used to treat other illnesses could be re-purposed to treat certain types of cancer.

Professor Lisanti said: "I was having a conversation with Camilla about how to cure cancer and she asked why don't we just use antibiotics like we do for other illnesses.

"I knew that antibiotics can affect mitochondria, but that conversation helped me to make a direct link.

"Camilla made a very broad generalisation, that adults wouldn't make, because they know too much.

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Girl aged just EIGHT helps scientist dad make cancer breakthrough after chat round dinner table

NEW YORK, Jan. 21, 2015 /PRNewswire/ --IntelliCell BioSciences, Inc.("IntelliCell" or the "Company") (OTCQB:SVFC), a regenerative medicine company utilizing adult autologous stromal vascular fraction cells (SVFCs) derived from the blood vessels found in adipose tissue, announced today an agreement for the development of a new closed processing system (the "System") for its cellular therapy manufacturing with Hielscher Ultrasonics. Under the agreement, Hielscher Ultrasonics will provide system design and engineering development for ultrasonic cavitation manufacturing, and IntelliCell Biosciences will use this system in its commercial application of its stromal vascular fraction cellular product, "SVFC."

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According to Dr. Steven Victor, CEO, "We are pleased to be partnering with Hielscher Ultrasonics and Tom Hielscher on the development of a new technology specifically designed to meet the needs of manufacturing in our cellular laboratory. By combining Hielscher's more than 20 years of process development and manufacturing experience with ultrasonic cavitation and Intellicell's experience in manufacturing SVFCs, we hope to produce a system that is patentable and makes the manufacturing process more streamline."

Thomas Hielscher states, "Hielscher Ultrasonics (www.hielscher.com) is the world's premier supplier of high performance, high quality ultrasonic devices. Hielscher Ultrasonics seeks to continually improve its products and services in order to fulfill their customers' needs. The permanent striving for improvement was the initiating step to develop an optimized ultrasonic reactor for IntelliCell's stem cell preparation."

In order to separate the stem cells and other beneficial cell types from the fat tissue, the harvested tissue is treated ultrasonically. The ultrasound cavitation technology can be adjusted exactly to the required intensity to break the tissue so that the cells are released for separation, but mildly enough to prevent the stem cells from damage.

To improve the ultrasonic cavitation technique, Hielscher developed for IntelliCell a unique ultrasonic reactor, which allows the sonication in a sterile, contamination-free environment.

About IntelliCell Biosciences

IntelliCell is a pioneering regenerative medicine company focused on the expanding regenerative medical markets using adult autologous stromal vascular fraction cells (SVFCs) derived from the blood vessels in the adult adipose tissue. IntelliCell BioSciences has developed its own patented technology and protocol to separate adult autologous vascular cells from adipose tissue without the use of enzymes. IntelliCell will also be seeking to develop technology-licensing agreements with technology developers, universities, and international business entities.

About Hielscher Ultrasonics

Hielscher Ultrasonicsis a family owned business, located in Teltow near Berlin (Germany). The main emphasis of its activities is the conception, development and production of ultrasonic devices for the use inlaboratoryandindustrialapplications. Technological innovations together with the realization of new ultrasound based processes substantiated the company growth and its market acceptance. Today, ultrasonic devices made by Hielscher Ultrasonics are being used in laboratories and production plants on all continents across the world. Hielscher Ultrasonics integrates the ultrasonic devices into complex ultrasonic systems, such aswire cleaning systems, too. The systems are produced to meet the customer's requirements in terms of power, extended range of accessories and steady state proof equipment (www.hielscher.com).

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IntelliCell BioSciences Announces Collaboration to Develop Closed Processing System for Cell Therapy Manufacturing

Roswell Park Cancer Institutes cutting-edge research into new therapies for advanced ovarian cancer has received a vote of confidence in the form of a major state grant.

This work shows promise in fighting a particularly deadly form of cancer and could help the Medical Campus develop a reputation as a center for innovative medical research.

The cancer institute has received a four-year, $11.9 million grant from New York State Stem Cell Science. The grant, according to the governors office, is part of a $36 million grant to three research groups for the development of treatments for some of the most devastating conditions that could be helped with stem cell research.

The local award is a nod to Roswell Park and Dr. Kunle Odunsi, executive director of the Center for Immunotherapy. But it is also a nod to the dedicated donors who raise money for the cancer center the Ride for Roswell is just one of many, many examples of those fundraising efforts. Approximately $2 million raised from Western New Yorkers helped to provide the pilot money for Odunsi to get the preliminary data so that he could generate his innovative premise and submit the proposal.

As Candace Johnson, Roswell Parks president and CEO, said, this is an especially important story because it shows how money raised at the grass-roots level has generated a much bigger commitment from the state.

Odunsis concept is so innovative that it might have been difficult to fund through traditional means, whether the National Institutes for Health or National Cancer Institute. That makes the dollars available from the New York State Stem Cell Science critical.

The Roswell Park project involves taking stem cells from the blood of cancer patients, re-engineering them and infusing them back into the patients to become a continuous source of cancer-fighting immune cells.

It is personalized medicine at its best. The Roswell Park team, led by Odunsi, has pushed the envelope of tradition, seeking to develop paradigm-changing therapies for ovarian cancer.

Ovarian cancer is one of the deadliest cancers for women. The American Cancer Society posted estimates for 2015: there will be about 21,290 new cases of ovarian cancer and 14,180 deaths.

The grant provides immediate funding to further study this ingenious approach and take it immediately to clinical trials, using some of the existing facilities at Roswell Park. It also allows the cancer center to retain researchers and fund some new positions, while potentially creating opportunities for commercial development.

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Major grant rewards Roswell Park for innovative research into immunotherapy

NEW YORK and PETACH TIKVAH, Israel, Jan. 5, 2014 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell technologies for neurodegenerative diseases, today announced positive final results from its phase 2a clinical trial of NurOwn in amyotrophic lateral sclerosis (ALS) patients, which enrolled 14 subjects at Hadassah Medical Center in Jerusalem.

The study achieved its primary endpoint in demonstrating that NurOwn is safe and well-tolerated at doses up to 2 million cells per kilogram administered intrathecally (IT) and 48 million cells administered intramuscularly (IM).

Importantly, nearly all subjects in this study experienced clinical benefit from treatment with NurOwn. Of the 12 subjects with three or more months of follow-up, 92% experienced an improvement in the rate disease progression for the three month period after administration of NurOwn, as measured by ALS Functional Rating Score-Revised (ALSFRS) or forced vital capacity (FVC). Fifty percent had an improvement in the slope of the ALSFRS score, and 67% had an improvement in the slope of the percent-predicted FVC.

NurOwn slowed the progression of ALS in this study, as indicated by an improving slope of both the mean ALSFRS and mean FVC curves after therapy. On ALSFRS, NurOwn slowed the rate of progression by 45%, from 1.41 points per month during the run-in period to 0.78 points per month for the three months following treatment, and by 57% to 0.60 per month for the six months following treatment. NurOwn had a similarly strong effect on the progressive loss of lung function the rate of decline in percent-predicted FVC was reduced by 73%, from an average of 2.60% per month during the run-in period to just 0.70% per month for the three months after treatment, and by 67% to 0.86% per month for the six months following treatment.

"We are gratified to have the final data from this study and are very encouraged by the results," commented BrainStorm's CEO Tony Fiorino, MD, PhD. "This study not only extends our earlier phase 1/2 findings regarding the safety of NurOwn, but also provide a consistent and highly promising picture of NurOwn's efficacy. In particular, I would highlight that we observed not only a highly meaningful reduction in ALS progression on mean ALSFRS and FVC, but we saw subjects with prolonged stabilization and even improvements in function, and all this was achieved with just a single dose of NurOwn. We are excited to proceed to a multi-dose study to see if these positive results can be amplified and extended by administering repeated doses."

Professor Dimitious Karussis of Hadassah Medical Center and the principal investigator of the trial, noted "This is the second study of NurOwn I have completed in ALS patients, and my excitement for these cells as a possible treatment for ALS continues to grow. I am impressed by the consistency of benefit of IT administration we have seen in both studies, and we saw in this study that almost every subject experienced clinical benefit, either on ALSFRS, FVC or both measures. I believe that if future studies demonstrate a similar magnitude of benefit, NurOwn will become an important treatment option for patients suffering from ALS."

About the Phase 2a Study

This was a single-arm, dose escalating study of NurOwn (also referred to as MSC-NTF cells) in ALS (see https://clinicaltrials.gov/show/NCT01777646 for more study details). The study enrolled 14 early-stage ALS patients into three ascending dose cohorts; each subject received NurOwn cells via IT and IM administration after a three month run-in period, and was then followed for six additional months after treatment. Subjects in this study were assessed at monthly visits by ALSFRS score and for respiratory function by FVC. The rate of decline for these measures was determined by calculating the slope of the linear regression line for the run-in period, the three month follow-up period, and the six month follow-up period.

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A cell programming technique developed at the Weizmann Institute turns them into the earliest precursors of sperm and ova

IMAGE:These are clusters of human embryonic stem cells that were differentiated to an early germ cell (PGC) state (colored cells). Each color reveals the expression of a different gene. (l-r)... view more

Credit: Weizmann Institute of Science

Groups at the Weizmann Institute of Science and Cambridge University have jointly managed the feat of turning back the clock on human cells to create primordial germ cells - the embryonic cells that give rise to sperm and ova - in the lab. This is the first time that human cells have been programmed into this early developmental stage. The results of their study, which were published today in Cell, could help provide answers as to the causes of fertility problems, yield insight into the earliest stages of embryonic development and potentially, in the future, enable the development of new kinds of reproductive technology.

"Researchers have been attempting to create human primordial germ cells (PGCs) in the petri dish for years," says Dr. Jacob Hanna of the Institute's Molecular Genetics Department, who led the study together with research student Leehee Weinberger. PGCs arise within the early weeks of embryonic growth, as the embryonic stem cells in the fertilized egg begin to differentiate into the very basic cell types. Once these primordial cells become "specified," they continue developing toward precursor sperm cells or ova "pretty much on autopilot," says Hanna. The idea of creating these cells in the lab took off with the 2006 invention of induced pluripotent stem (iPS) cells - adult cells that are "reprogrammed" to look and act like embryonic stem cells, which can then differentiate into any cell type. Thus several years ago, when researchers in Japan created mouse iPS cells and then got them to differentiate into PGCs, scientists immediately set about trying to replicate the achievement in human cells. But until now, none had been successful.

Previous research in Hanna's lab pointed to new methods that could take human cells to the PGC state. That research had focused on the question of how human iPS cells and mouse embryonic cells differ: The mouse embryonic cells are easily kept in their stem cell state in the lab, while human iPS cells that have been reprogrammed - a technique that involves the insertion of four genes - have a strong drive to differentiate, and they often retain traces of "priming." Hanna and his group then created a method for tuning down the genetic pathway for differentiation, thus creating a new type of iPS cell that they dubbed "nave cells." These nave cells appeared to rejuvenate iPS cells one step further, closer to the original embryonic state from which they can truly differentiate into any cell type. Since these nave cells are more similar to their mouse counterparts, Hanna and his group thought they could be coaxed to differentiate into primordial germ cells.

Working with nave human embryonic stem and iPS cells, and applying the techniques that had been successful in the mouse cell experiments, the research team managed to produce cells that, in both cases, appeared to be identical to human PGCs. Together with the lab group of Prof. Azim Surani of Cambridge University, the scientists further tested and refined the method jointly in both labs. By adding a glowing red fluorescent marker to the genes for PGCs, they were able to gauge how many of the cells had been programmed. Their results showed that quite a high rate - up to 40% - had become PGCs; this quantity enables easy analysis.

Hanna points out that PGCs are only the first step in creating human sperm and ova. A number of hurdles remain before labs will be able to complete the chain of events that move an adult cell through the cycle of embryonic stem cell and around to sperm or ova. For one, at some point in the process, these cells must learn to perform the neat trick of dividing their DNA in half before they can become viable reproductive cells. Still, he is confident that those hurdles will one day be overcome, raising the possibility, for example, of enabling women who have undergone chemotherapy or premature menopause to conceive.

In the meantime, the study has already yielded some interesting results that may have significant implications for further research on PGCs and possibly other early embryonic cells. The team managed to trace part of the genetic chain of events that directs a stem cell to differentiate into a primordial germ cell, and they discovered a master gene, Sox17, that regulates the process in humans, but not in mice. Because this gene network is quite different from the one that had been identified in mice, the researchers suspect that more than a few surprises may await scientists who study the process in humans.

Hanna: "Having the ability to create human PGCs in the petri dish will enable us to investigate the process of differentiation on the molecular level. For example, we found that only 'fresh' nave cells can become PGCs; but after a week in conventional growth conditions they lose this capability once again. We want to know why this is. What is it about human stem cell states that makes them more or less competent? And what exactly drives the process of differentiation once a cell has been reprogrammed to its more nave state? It is the answers to these basic questions that will, ultimately, advance iPS cell technology to the point of medical use."

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Human primordial cells created in the lab