The-Scientist.com, January 27, 2010, by Bob Grant  —  When he addresses the nation tonight (27th January), US President Obama is expected to call for a three-year freeze on federal spending for any programs not dealing with the military or homeland defense. But with the budget boosts for federal science agencies provided by 2009’s American Recovery and Reinvestment Act drying up in 2011, science advocates are concerned that Obama’s funding freeze may spell the steep budgetary drop-off in the next fiscal year that many dread.
“Certainly it does concern us,” Kerry Peluso, associate vice president for research administration at Emory University in Atlanta, told The Scientist. “We want to see our researchers continue to be able to do their research.”

Though the announcement is not yet official, the White House has released some details of the proposed freeze in the run up to Obama’s State of the Union address tonight and the release of his FY2011 budget proposal, which is slated for Monday (1st February). “The three-year freeze over the course of 10 years will save on the order of $250 billion,” said press secretary Robert Gibbs at a White House press briefing yesterday.

In an entry posted yesterday on The White House Blog, Vice President Joe Biden’s chief economist and economic policy adviser Jared Bernstein said that Obama’s freeze would be more like surgery and less like a hatchet job. “…the entire theory of the President’s proposed freeze is to dial up the stuff that will support job growth and innovation while dialing down the stuff that doesn’t,” Bernstein wrote. “Under our plan, some discretionary spending will go up; some will go down. That’s a big difference from a hatchet.”

But some aren’t entirely convinced that science funding will be spared the axe. “We are extremely concerned about the proposed freeze on non-security discretionary spending, particularly in light of the compelling evidence that an innovation-driven economy is the future,” said Mary Woolley, president and CEO of science advocacy group Research!America. “We’re looking to the President for national priority-setting that’s consistent with that goal.”

The Federation of American Societies for Experimental Biology (FASEB), another science advocacy organization, is holding out hope that Obama’s past statements on the importance of science and research in rebuilding the economy portend a reprieve for federal research funding agencies, such as the National Institutes of Health and the National Science Foundation. “We’re hopeful that science is enough of a priority in the president’s agenda that the scientific agencies we care about will not be included [in the freeze],” FASEB spokesperson Carrie Wolinetz told The Scientist. “It’s something that we’re waiting to hear more details about.”

Alzheimer’s Disease: Another example of the atrophy and enlarged ventricles seen in Alzheimer’s disease.
Alzheimer’s can be seen in a presenile form, that is, before the age of 65.
Note the dark substantia nigra suggesting that this does not have accompanying Parkinson’s disease.  Description By:Margaret Grunnet,M.D., (Image Contrib. by: UCHC )

Alzheimer’s Disease – Closeup of a senile plaque (arrows), showing stick like abnormal neurites collected in a ball.
Because it has no amyloid center, this type of plaque is known as a diffuse plaque.

Description By:Margaret Grunnet,M.D., Image Contrib. by:Margaret Grunnet,M.D. UCHC

Emory University, January 26, 2010  —  Alzheimer’s disease (AD) researchers are testing the effectiveness of gene therapy for the first time to treat patients with this common brain disease. Emory University is one of 12 institutions participating in a nationwide study to test the experimental medication, CERE-110.

The Phase 2 clinical trial seeks to enroll a total of 50 study participants with mild to moderate AD.

Previously studied in animals and in a small study to assess safety in humans, CERE-110 appears to induce long-term production of Nerve Growth Factor (NGF) by brain cells. NGF is a naturally occurring protein that helps nerve cells, or neurons, survive in the brain. These neurons produce a chemical, acetylcholine, which plays a vital role in memory and cognitive function.

“Since NGF supports the survival and function of the neurons that deteriorate in people with Alzheimer’s disease, we hope to slow the worsening of their symptoms with this new therapy,” says James Lah, MD, associate professor of neurology, Emory University School of Medicine and lead investigator of the study at Emory.

During the Phase 2 clinical trial, a neurosurgeon will inject CERE-110 directly into the nucleus basalis of Meynert (NBM) of the brain, an area where neuron death occurs in AD. CERE-110 packages the gene for NGF within a shell from the adeno-associated virus. Putting an extra copy of the NGF gene into cells drives them to make more NGF. The original virus is not known to cause disease — and as an extra precaution, most of the insides of the virus are removed.

“Adeno-associated viral vectors like the one used in this study have proven safe in extensive animal testing, as well as several other human trials for neurodegenerative diseases,” says Nicholas Boulis, MD, assistant professor, department of neurosurgery, Emory University School of Medicine. Boulis has previously conducted neurosurgical adeno-associated gene therapy and is performing the surgery in the Emory study.

A Phase 1 study was conducted where the treatment was found to be generally safe and well tolerated. The 10 subjects underwent cognitive testing, measures of activities of daily living, and MRI and PET (positron emission tomography) scans. Researchers observed increases in brain metabolism in several cortical regions of the brain at six months and 12 months in some of the participants, as compared to other severity-matched individuals with AD, suggesting a potential reversal of patterns typically observed in AD. With follow up ranging from six months to more than four years post-treatment, there have been no side effects thought to be caused by CERE-110.

In previous studies, CERE-110 reversed brain degeneration in aged animals and in animal models intended to create cholinergic degeneration, a feature that characterizes changes in early AD. The overall study is conducted by the Alzheimer’s Disease Cooperative Study (ADCS), a nationwide consortium of research centers and clinics supported by the National Institute on Aging (NIA), National Institutes of Health, and coordinated by the University of California San Diego. Ceregene, Inc., the study sponsor, is a San Diego-based biotechnology company providing CERE-110 for the study.

Weill Cornell Medical College Study Lays Groundwork for New Treatments for Cardiovascular Disease and Other Conditions

Rendering of blood flowing in a blood vessel. In a significant step toward restoring healthy blood circulation to treat a variety of diseases, a team of scientists at Weill Cornell Medical College has developed a new technique and described a novel mechanism for turning human embryonic and pluripotent stem cells into plentiful, functional endothelial cells, which are critical to the formation of blood vessels. (Credit: iStockphoto/Osman Safi)

 

Cornell Scientists Create Usable Blood Vessels from Human Stem Cells

 

 

Weill-Cornell Medical College, NEW YORK (Jan. 26, 2010) — In a significant step toward restoring healthy blood circulation to treat a variety of diseases, a team of scientists at Weill Cornell Medical College has developed a new technique and described a novel mechanism for turning human embryonic and pluripotent stem cells into plentiful, functional endothelial cells, which are critical to the formation of blood vessels. Endothelial cells form the interior “lining” of all blood vessels and are the main component of capillaries, the smallest and most abundant vessels. In the near future, the researchers believe, it will be possible to inject these cells into humans to heal damaged organs and tissues.

The new approach allows scientists to generate virtually unlimited quantities of durable endothelial cells — more than 40-fold the quantity possible with previous approaches. Based on insights into the genetic mechanisms that regulate how embryonic stem cells form vascular endothelial cells, the approach may also yield new ways to study genetically inherited vascular diseases. The study appears in the advance online issue of Nature Biotechnology.

“This technique is the first of its kind with serious potential as a treatment for a diverse array of diseases, especially cardiovascular disease, stroke and vascular complications of diabetes,” says Dr. Shahin Rafii, the study’s senior author. Dr. Rafii is the Arthur B. Belfer Professor in Genetic Medicine and co-director of the Ansary Stem Cell Institute at Weill Cornell Medical College, and an investigator of the Howard Hughes Medical Institute.

In recent years, enormous hopes have been pinned on stem cells as the source of future cures and treatments. Indeed, human embryonic stem cells have the potential to become any one of the more than 200 types of adult cells. However, the factors and pathways that govern their differentiation to abundant derivatives that could be used to repair organs have remained poorly understood.

A major challenge for Dr. Rafii’s lab has been to improve their understanding, and hence control, of the differentiation process (how stem cells convert to various cell types), and then to generate enough vascular endothelial cells — many millions — so they can be used therapeutically.

To meet this challenge, the scientists first screened for molecular factors that come into play when stem cells turn into endothelial cells. Their findings led them to a strategy that significantly boosts the efficiency of producing these cells.

Then, the researchers tracked the differentiation process in real-time using a green fluorescent protein marker developed by Dr. Daylon James, the study’s first author and assistant research professor in the Department of Reproductive of Medicine at Weill Cornell Medical College. They found that when they exposed stem cells to a compound that blocks TGF-beta (a growth factor involved in cell specialization) at just the right time during cell culturing, the propagation of endothelial cells dramatically increased.

Even more striking, they found that the cells worked properly when injected into mice. The cells were quickly assimilated into the animals’ circulatory systems, and functioned alongside normal vasculature.

To achieve long-lasting clinical benefits, there remain additional hurdles to exploiting endothelial cells generated in vitro. Indeed, a fundamental prerequisite to using vascular cells in regenerative medicine has been the proper assembly in vivo of new blood vessels from stem-cell-derived cells, according to Dr. Sina Rabbany, who is an adjunct professor at Weill Cornell Medical College and professor of bioengineering at Hofstra University. Dr. Rabbany emphasizes that, in addition to manipulating biological factors implicated in endothelial cell differentiation, the impact of blood flow on endothelial cells is critical to engineering durable, vascularized organs. With the plentiful supply of endothelial cells that the new methods provide, Dr. Rabbany’s team is working to build biological scaffolds that model the microenvironment of the vasculature, so that the vessels they generate will be functional and long-lasting in patients.

Another major obstacle to clinical use of cultured endothelial cells is the potential of immune rejection when the cells are injected into a patient. To address this risk, one approach would be to create a large, genetically diverse bank of human embryonic stem cells that, on demand, could be converted into endothelial cells that are compatible with specific patients.

“Given the success rate our group has shown in generating human embryonic stem cells from donated normal and diseased embryos, this new approach has broad implications not only for regenerative medicine, but also for the study of genetic diseases of the vasculature,” states Dr. Zev Rosenwaks, who is director and physician-in-chief of the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine as well as the director of the Tri-Institutional Stem Cell Initiative Derivation Unit at Weill Cornell Medical College.

The new endothelial cell culture is currently being validated in ongoing research at Weill Cornell using a number of stem cell “lines,” or “families” of stem cells. “Employing a highly sophisticated derivation technology, we have been able to generate 11 normal and diseased human embryonic cell lines from discarded embryos at the Tri-Institute Derivation Unit at Weill Cornell,” states Dr. Nikica Zaninovic, an assistant professor at the Department of Reproductive of Medicine who is spearheading the human embryonic stem cell derivation effort. Using the new differentiation methods, several of these new embryonic stem cell lines have been turned into vascular cells.

Testing in humans is the next major step in verifying the ability of this breakthrough cell-based approach to restore blood supply to injured organs. Armed with this new technology and under the umbrella of support from the Ansary Stem Cell Institute and Tri-Institutional Stem Cell Initiative (Tri-SCI), this team of scientists is hoping to transfer their methods to the clinic within the next five years.

The current study sheds light on the generation of human embryonic vasculature in ways that have not previously been feasible due to obstacles associated with the use of human embryonic tissue. As Dr. James explains, “The unbiased screening technique we used is a major technological advance that opens up possibilities for discovery of how human embryonic stem cells morph into the specific mature cells that compose the brain, liver, pancreas, and so on. Our general approach can be applied to additional human tissues and help other stem cell research groups develop and maintain specialized cell types in the larger effort to understand human development — and to heal many different kinds of human diseases and injuries.”

The Tri-Institutional Stem Cell Initiative, supported by a generous gift from The Starr Foundation, is a collaborative venture of Memorial Sloan-Kettering Cancer Center, The Rockefeller University, and Weill Cornell Medical College.

Ansary Stem Cell Institute

The Ansary Stem Cell Institute, established at Weill Cornell Medical College in 2004 through the generous donation of Shahla and Hushang Ansary, brings together a premier team of scientists to focus on stem cells — the primitive, unspecialized cells with an unrivaled capacity to form all types of cells, tissues and organs in the body. The vision of the Ansary Institute is to help lead the way in 21st-century medicine by employing this new field of research with tremendous potential to relieve human suffering. The Institute permits the multidisciplinary collaboration and creativity of Weill Cornell’s researchers, as well as helps to attract the best and brightest young researchers in the field. Scientists at the Institute hope to discover the wellspring of adult stem cells in the body and ways to manipulate them to treat human illness. In particular, they hope to understand the regulation of cells that give rise to such essential components as blood vessels, insulin-producing cells in the pancreas (which are damaged in diabetics), and neurons of the brain and nervous system.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University’s medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson’s disease, and most recently, the world’s first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston, making Weill Cornell one of only two medical colleges in the country affiliated with two U.S.News & World Report Honor Roll hospitals. For more information, visit www.med.cornell.edu.  Contact Info: Andrew Klein ank2017@med.cornell.edu

Read more………………..

 

New Way to Generate Abundant Functional Blood Vessel Cells from Human Stem Cells Discovered

 

ScienceDaily.com — In a significant step toward restoring healthy blood circulation to treat a variety of diseases, a team of scientists at Weill Cornell Medical College has developed a new technique and described a novel mechanism for turning human embryonic and pluripotent stem cells into plentiful, functional endothelial cells, which are critical to the formation of blood vessels.

Endothelial cells form the interior “lining” of all blood vessels and are the main component of capillaries, the smallest and most abundant vessels. In the near future, the researchers believe, it will be possible to inject these cells into humans to heal damaged organs and tissues.

The new approach allows scientists to generate virtually unlimited quantities of durable endothelial cells — more than 40-fold the quantity possible with previous approaches. Based on insights into the genetic mechanisms that regulate how embryonic stem cells form vascular endothelial cells, the approach may also yield new ways to study genetically inherited vascular diseases. The study appears in the advance online issue of Nature Biotechnology.

“This technique is the first of its kind with serious potential as a treatment for a diverse array of diseases, especially cardiovascular disease, stroke and vascular complications of diabetes,” says Dr. Shahin Rafii, the study’s senior author. Dr. Rafii is the Arthur B. Belfer Professor in Genetic Medicine and co-director of the Ansary Stem Cell Institute at Weill Cornell Medical College, and an investigator of the Howard Hughes Medical Institute.

In recent years, enormous hopes have been pinned on stem cells as the source of future cures and treatments. Indeed, human embryonic stem cells have the potential to become any one of the more than 200 types of adult cells. However, the factors and pathways that govern their differentiation to abundant derivatives that could be used to repair organs have remained poorly understood.

A major challenge for Dr. Rafii’s lab has been to improve their understanding, and hence control, of the differentiation process (how stem cells convert to various cell types), and then to generate enough vascular endothelial cells — many millions — so they can be used therapeutically.

To meet this challenge, the scientists first screened for molecular factors that come into play when stem cells turn into endothelial cells. Their findings led them to a strategy that significantly boosts the efficiency of producing these cells.

Then, the researchers tracked the differentiation process in real-time using a green fluorescent protein marker developed by Dr. Daylon James, the study’s first author and assistant research professor in the Department of Reproductive of Medicine at Weill Cornell Medical College. They found that when they exposed stem cells to a compound that blocks TGF-beta (a growth factor involved in cell specialization) at just the right time during cell culturing, the propagation of endothelial cells dramatically increased.

Even more striking, they found that the cells worked properly when injected into mice. The cells were quickly assimilated into the animals’ circulatory systems, and functioned alongside normal vasculature.

To achieve long-lasting clinical benefits, there remain additional hurdles to exploiting endothelial cells generated in vitro. Indeed, a fundamental prerequisite to using vascular cells in regenerative medicine has been the proper assembly in vivo of new blood vessels from stem-cell-derived cells, according to Dr. Sina Rabbany, who is an adjunct professor at Weill Cornell Medical College and professor of bioengineering at Hofstra University. Dr. Rabbany emphasizes that, in addition to manipulating biological factors implicated in endothelial cell differentiation, the impact of blood flow on endothelial cells is critical to engineering durable, vascularized organs. With the plentiful supply of endothelial cells that the new methods provide, Dr. Rabbany’s team is working to build biological scaffolds that model the microenvironment of the vasculature, so that the vessels they generate will be functional and long-lasting in patients.

Another major obstacle to clinical use of cultured endothelial cells is the potential of immune rejection when the cells are injected into a patient. To address this risk, one approach would be to create a large, genetically diverse bank of human embryonic stem cells that, on demand, could be converted into endothelial cells that are compatible with specific patients.

“Given the success rate our group has shown in generating human embryonic stem cells from donated normal and diseased embryos, this new approach has broad implications not only for regenerative medicine, but also for the study of genetic diseases of the vasculature,” states Dr. Zev Rosenwaks, who is director and physician-in-chief of the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine as well as the director of the Tri-Institutional Stem Cell Initiative Derivation Unit at Weill Cornell Medical College.

The new endothelial cell culture is currently being validated in ongoing research at Weill Cornell using a number of stem cell “lines,” or “families” of stem cells. “Employing a highly sophisticated derivation technology, we have been able to generate 11 normal and diseased human embryonic cell lines from discarded embryos at the Tri-Institute Derivation Unit at Weill Cornell,” states Dr. Nikica Zaninovic, an assistant professor at the Department of Reproductive of Medicine who is spearheading the human embryonic stem cell derivation effort. Using the new differentiation methods, several of these new embryonic stem cell lines have been turned into vascular cells.

Testing in humans is the next major step in verifying the ability of this breakthrough cell-based approach to restore blood supply to injured organs. Armed with this new technology and under the umbrella of support from the Ansary Stem Cell Institute and Tri-Institutional Stem Cell Initiative (Tri-SCI), this team of scientists is hoping to transfer their methods to the clinic within the next five years.

The current study sheds light on the generation of human embryonic vasculature in ways that have not previously been feasible due to obstacles associated with the use of human embryonic tissue. As Dr. James explains, “The unbiased screening technique we used is a major technological advance that opens up possibilities for discovery of how human embryonic stem cells morph into the specific mature cells that compose the brain, liver, pancreas, and so on. Our general approach can be applied to additional human tissues and help other stem cell research groups develop and maintain specialized cell types in the larger effort to understand human development — and to heal many different kinds of human diseases and injuries.”

The Tri-Institutional Stem Cell Initiative, supported by a generous gift from The Starr Foundation, is a collaborative venture of Memorial Sloan-Kettering Cancer Center, The Rockefeller University, and Weill Cornell Medical College.  Source: Adapted from materials provided by New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College.