Stem Cell Advances

Any adult cell can become a stem cell. This is a striking finding from the Cambridge, Mass. researchers.

“Essentially, all cells have the potential to become pluripotent. It is something that seems to happen to the cells under these conditions stochastically — that is, in a continuous, but probabilistic fashion,” Jaenisch explains. _Softpedia

Stem cell treatment restores limb function in rats with cervical spine injuries. The UCI team used human embryonic stem cells (pre-oligodendrocytes) that "rebuilt myelin, stopped tissue death and triggered nerve fiber regrowth".

Patients with advanced leukemia successfully treated with stem cells. Of the 58 patients, 35% survived 3 years -- an exceptionally good result for patients at such an advanced stage.

New technique developed to separate "safe" from "unsafe" stem cells before therapy. Stem cells vary in their likelihood to grow out of control and cause malignancies. "Undifferentiated" stem cells are more likely to lose control of growth.

Scientists from Invitrogen and the Buck Institute for Age Research, located in Novato, California, collaborated in developing this innovative solution that depletes greater than 99% of undifferentiated human embryonic stem cells from differentiated populations. They are presenting data on this new technology at the International Society for Cellular Therapy Meeting in San Diego. __LabmateOnline

Stem cells provide the bricks and mortar for constructing human tissues and organs. We are just beginning to learn how to create them, and to use them safely and efficaciously. In ten years -- if the US biomedical system has not been completely destroyed by government intervention -- we will look back to the present, amazed that human medicine was ever so primitive and hopelessly ineffective.

SENS4 Conference in Cambridge England Underway

Kristen Fortney from Ouroborus blog is covering the 4th Strategies for Engineered Negligible Senescence conference, presently underway in Cambridge, England. Below are some excerpts of Kristen's coverage, courtesy of Fight Aging:

SENS4, Session 1: Combating oxidation

Cathy Clarke tested an original and interesting approach to avoiding free radical damage to poly-unsaturated fatty acids, or PUFAs: isotope reinforcement. ... The basic idea here, explained in an earlier paper, is very simple: heavier isotopes make stronger bonds, so isotope-reinforced PUFAs will be more resistant to free radical attack. Will these results transfer to higher organisms? Is there any chance that the deuterium could get incorporated into other molecules, stabilizing proteins that we want to degrade? The authors plan to follow up this study in worms and mice.

SENS4, Session 3: Optimising metabolism against aging

Stephen Spindler described his (ongoing) project to screen a large number of potential lifespan-affecting compounds in mice - so far, several candidates look promising. Interestingly, he also argued that the majority of previous studies measuring the effects of various compounds on rodent life expectancy suffer from serious flaws. In particular, he argued that many of them were confounded by a possible calorie restriction effect: mice are picky eaters, and if you change their diet by adding some compound to it, they will often eat less of it.

SENS4, Session 4: Adult regenerative capacity

Brandon Reines presented a counterintuitive result on regeneration: sometimes old animals have a higher regenerative capacity than young animals. In particular, if you punch a hole in the ear of a young mouse, then it won’t heal; but in a middle-aged mouse it will heal completely. He argued that this happens because mouse ear connective tissues never fully differentiate, and suggested that other neural-crest-derived connective tissues might show similar properties.

SENS4, Session 5: Eliminating recalcitrant intracellular molecules: the lysosome

John Schloendorn discussed ongoing work at the SENS Foundation Research Center to develop new enzymes that can degrade harmful intracellular junk that accumulates with age. So far, they have discovered enzymes that can degrade A2E and 7-ketocholesterol, which are implicated in macular degeneration and osteoporosis, respectively. Their next step will be to construct a drug delivery system to get these enzymes to lysozomes ... On the lighter side, Schloendorn also described some of the Center’s methods for building functional lab equipment on the cheap, all good examples for aspiring DIY biologists.

SENS4, Session 6: Eliminating recalcitrant intracellular molecules: other

Claude Wischik spoke about preventing aggregation of tau protein, which is implicated in Alzheimer’s disease. Clinical trials of their aggregation-inhibiting drug Rember are promising: it seems to slow the down the rate of cognitive decline in patients with mild to moderate Alzheimer’s disease.

SENS4, Sessions 9 and 10: Rejuvenating extracellular material

Kendall Houk gave a very interesting talk on computationally designing enzymes from scratch. They plan to apply their recently published protocol to develop enzymes that can reverse the formation of Advanced Glycation End-products (AGEs) - sugar-modified proteins that accumulate with age and are implicated in several age-related diseases. _links to more information

Ouroborus is updating Kristen's coverage as it comes in.

Twitter updates

Aubrey de Grey's SENS initiative has achieved prominence in scientific gerontology, thanks to financing from the Methuselah Foundation. Under most government health care and pension systems, long life is a bad thing, since the longer you live, the longer the government has to support your existence. That may be why so little progress was made under government financed gerontology research.

With private funding via SENS, expect much more progress. The same applies to private financing of space launch, and other crucial innovations. The private sector is all about getting results. The government is all about soaking up as many resources as possible, growing as large as possible, and employing as many public sector union members as possible.

Cross posted at Al Fin

Giving Babies Healthy Mitochondria

Scientists at the Oregon National Primate Center have succeeded in producing healthy rhesus infants using the egg nucleus from one female transplanted into the enucleated cytoplasm of another female. The mitochondria from the cytoplasmic component reproduced normally alongside the nuclear material from the nuclear component, without contamination of mitochondria from the nucleus donour.

For their experiments, Mitalipov and his colleagues extracted DNA from the nucleus of monkey eggs; the nucleus contains the genes for most of a creature's traits. The researchers then transplanted that DNA into eggs from other females that had healthy mitochondrial DNA but from which the nuclear DNA had been removed.

They then fertilized the eggs in the laboratory and transferred 15 of the resulting embryos into the wombs of nine females. Two twins were born -- named Mito and Tracker -- along with two other offspring, Spindler and Spindy. So far, all the offspring appear to be healthy. _WaPo_via_ImpactLat

This research shows the way to new techniques for using cytoplasmic donour eggs to assure healthy offspring for mothers who may carry deficiencies for mitochondria -- which have their own DNA, for the most part.

Assuring mitochondrial health is one of the most important bases for overall health and longevity.

While this technique will only work for animals at the egg stage, there is no reason not to believe that advanced forms of mitochondrial culturing and transplant will not occur. Eventually, interventional genetic therapies will be developed which will move most of the genetic material from the mitochondria -- where it is subjected to extreme mutagenic oxidative stress -- to the nucleus where it would be better protected. That is one of the foundations of the SENS approach to longevity.

Hope for the Aging Brain

An intriguing finding from the University of South Florida offers new hope for rejuvenating aged and amyloid-clogged brains.

GCSF is a blood stem cell growth factor or hormone routinely administered to cancer patients whose blood stem cells and white blood cells have been depleted following chemotherapy or radiation. GCSF stimulates the bone marrow to produce more white blood cells needed to fight infection. It is also used to boost the numbers of stem cells circulating in the blood of donors before the cells are harvested for bone marrow transplants. Advanced clinical trials are now investigating the effectiveness of GCSF to treat stroke, and the compound was safe and well tolerated in early clinical studies of ischemic stroke patients.

....The researchers showed that injections under the skin of filgrastim (Neupogen®) — one of three commercially available GCSF compounds — mobilized blood stem cells in the bone marrow and neural stem cells within the brain and both of these actions led to improved memory and learning behavior in the Alzheimer’s mice. “The beauty in this less invasive approach is that it obviates the need for neurosurgery to transplant stem cells into the brain,” Dr. Sanchez-Ramos said.

Based on the promising findings in mice, the Alzheimer’s Drug Discovery Foundation is funding a pilot clinical trial at USF’s Byrd Alzheimer’s Center. The randomized, controlled trial, led by Dr. Sanchez-Ramos and Dr. Ashok Raj, will test the safety and effectiveness of filgrastim in 12 patients with mild to moderate Alzheimer’s disease _Biosingularity

As noted, the reversal of Alzheimer's brain damage occurred in research mice -- a mouse "Alzheimer's model" involving 52 aged study mice. If the trial involving 12 human patients shows promise, expect several larger human studies.

In my opinion, Alzheimer's Disease is every bit the crisis that AIDS represents, and the search for therapies for Alzheimer's should be given at least as much funding and regulatory impetus as the research effort into HIV and AIDS has been given. Unfortunately, President Obama and his administration are sending signals that advanced medical care for the aged will be given an extremely low priority under Obamacare.

Another stem cell growth factor -- EGFL7 -- may play a large role in therapies for a wide array of conditions involving brain degeneration and damage.

The findings of Schmidt and Dikic offer a plethora of medical applications. Maturation of adult stem or precursor cells is significant for the development of multiple tissues, e.g. in the central nerve system or in the heart. Moreover, cancer stem cells have been described, which are important for the formation of tumors, especially in the human brain. EGFL7 might also be applied as a neuronal differentiation factor in ischemic insults or neurodegenerative diseases such as Alzheimer or Parkinson predict both researchers. Future work will unravel in which diseases EGFL7 can unfold its therapeutic potential. _Biosingularity

We are likely to find dozens of growth factors and differentiation factors that will come into play in the reversal of degenerative, traumatic, and age-related diseases of the brain. It will take time, investment, and long hours of dedicated research by an army of bright and well-trained researchers with open minds.

It is also important to eat the right foods, and to get plenty of exercise. Thinking "young" can also keep the brain more vital. Seek out new experiences and adventures. Try new foods, travel within your means, renew old friendships and make new ones.

It is easy to tell the difference between people who have given up, and those who will be scrapping right up to the end. Try to be a scrapper.

Will This Metallomolecule Help to Extend Life?

Perhaps it will extend life. It can kill cancer, kill deadly resistant microbes, and may become a key part of the SENS anti-aging platform. Here is how:

The compound [Fe2L3]4+ is an iron triple helicate with three organic strands wrapped around two iron centres to give a helix which looks cylindrical in shape and neatly fits within the major groove of a DNA helix. It is about the same size as the parts of a protein that recognise and bind with particular sequences of DNA. The high positive charge of the compound enhances its ability to bind to DNA which is negatively charged.

When the iron-helicate binds to the major groove of DNA it coils the DNA so that it is no longer available to bind to anything else and is not able to drive biological or chemical processes. _PO

The interesting structure known as [Fe(2)L(3)](4+) was first researched as a treatment for cancer. But University of Warwick researchers have discovered that the metallomolecule is a particularly potent killer of bacteria -- even bacteria that are resistant to conventional antibiotics.

Initially the researchers focused on the application of this useful property for targeting the DNA of cancer cells as it could bind to, coil up and shut down the cancer cell's DNA either killing the cell or stopping it replicate. However the team quickly realised that it might also be a very clever way of targeting drug-resistant bacteria.

New research at the University of Warwick, led by Dr Adair Richards and Dr Albert Bolhuis, has now found that the [Fe2L3]4+ does indeed have a powerful effect on bacteria. When introduced to two test bacteria Bacillus subtilis and E. coli they found that it quickly bound to the bacteria's DNA and killed virtually every cell within two minutes of being introduced - though the concentration required for this is high. _PO

It will be important for the researchers to learn ways that the compound can be preferentially transported across bacterial membranes, to bacterial DNA. By reducing the necessary concentrations needed to kill the bacteria, and by making the construct preferentially attracted to pathological bacteria rather than to normal human cells, the safety and the efficacy of any possible future treatment using this compound will be enhanced.

The prevalence of antibiotic resistance has resulted in the need for new approaches to be developed to combat previously easily treatable infections. Here we investigated the potential of the synthetic metallomolecules [Fe(2)L(3)](4+) and [Cu(2)(L')(2)](2+) as antibacterial agents.... [Fe(2)L(3)](4+) binds in the major groove and causes DNA coiling... The work described here shows that ... [Fe(2)L(3)](4+) is bactericidal for Bacillus subtilis and Escherichia coli. We demonstrate that [Fe(2)L(3)](4+) binds bacterial DNA in vivo and, strikingly, that it kills B. subtilis cells very rapidly. _IntJnlAntimicrobialAgents

Cytocidal approaches are valuable medically to the extent they can be targeted and controlled -- with only limited damage to normal cells and tissues.

One of the main pillars of the SENS anti-aging approach is the elimination of superfluous and dangerous cells that have outlived their usefulness. The more precisely that one can target cytotoxic molecules, the more useful they will be for anti-aging therapies in addition to more conventional medical disciplines such as oncology and infectious disease.

Cross-posted at Al Fin

Regenerative Medicine Gets a Boost

Blood disorders are likely to be the first targets for therapy because corrected cells can easily be transferred back to the patient via bone-marrow transplants. _TechnologyReview

Salk Institute researchers in La Jolla have demonstrated a technique that opens the door to cures for several genetic blood diseases. It involves taking a patient's skin cells, treating them genetically to correct the inherited disorder, next turning the skin cells into induced pluripotent stem cells (iPS), then differentiating those iPS into progenitor cells. These progenitor cells can be implanted into the patient to provide a supply of normal blood cells.

"This is an exciting bit of science," says Chris Mason, a professor of regenerative medicine at University College London, who was not directly involved in the research. "It's likely to be the first of a slew of similar papers that may offer hope for conditions where today there is no real therapy, let alone a cure."

So far, Belmonte's approach is applicable only to diseases in which the genetic defect that underlies the disease has been identified. "But there are quite a few of these--and the number will increase," says Mason. Blood disorders are likely to be the first targets for therapy because corrected cells can easily be transferred back to the patient via bone-marrow transplants.

Belmonte adds that in the future, the correction of more-complex genetic disorders might become possible, thereby significantly increasing the number of diseases that might be treated with altered iPS cells. _TechnologyReview

If the bone marrow can be "re-stocked" with viable normal blood progenitor cells, the inherited blood disorder may indeed be cured. The concept can be extended to other inherited and acquired genetic diseases with extensive work.

Such approaches to cell and tissue replacement open the door to significant extension of maximum life span.

Taken from an earlier post at Al Fin

Tiny Porous Nano-Spheres Carry 2 Drugs at Once

Ames Lab researchers at Iowa State University continue their work with porous silica nano-spheres as drug delivery systems. This time, they have devised nano-systems capable of delivering two different drugs simultaneously.

A boronic acid-functionalized mesoporous silica nanoparticle-based drug delivery system (BA-MSN) for glucose-responsive controlled release of both insulin and cyclic adenosine monophosphate (cAMP) was synthesized. Fluorescein isothiocyanate-labeled, gluconic acid-modified insulin (FITC-G-Ins) proteins were immobilized on the exterior surface of BA-MSN and also served as caps to encapsulate cAMP molecules inside the mesopores of BA-MSN. The release of both G-Ins and cAMP was triggered by the introduction of saccharides. The selectivity of FITC-G-Ins release toward a series of carbohydrate triggers was determined to be fructose > glucose > other saccharides. The unique feature of this double-release system is that the decrease of FITC-G-Ins release with cycles can be balanced by the release of cAMP from mesopores of MSN, which is regulated by the gatekeeper effect of FITC-G-Ins. In vitro controlled release of cAMP was studied at two pH conditions (pH 7.4 and 8.5). Furthermore, the cytotoxicity of cAMP-loaded G-Ins-MSN with four different cell lines was investigated by cell viability and proliferation studies. The cellular uptake properties of cAMP-loaded FITC-BA-MSN with and without G-Ins capping were investigated by flow cytometry and fluorescence confocal microscopy. We envision that this glucose-responsive MSN-based double-release system could lead to a new generation of self-regulated insulin-releasing devices. _ACS

The ability to release two interacting substances from separate compartments in a nano-delivery system, provides for much longer shelf life and greater potency at the time of delivery. In this case, the payoff will be stop-gap implantable blood glucose regulation.

For long term control of diabetes, working cellular systems that can synthesise their own insulin are preferable to artificial systems. In general, the same principle is valid for all replacement organs and systems.

Replacement parts that can repair themselves, and work in concert with the rest of the body, are preferable to "one trick pony" replacements that too easily give out.

Almost certainly the best use of the Ames nano-spheres will be for genetic therapies to permanently alter gene expression of cells and tissues. But for now, proving the extent of functionality of this delivery system remains important.

50 Best Anti-Ageing Blogs

The Ultrasound Technician Schools blog has put together a list of the 50 top anti-ageing blogs, for those who want to follow the broad range of online approaches to ageing and longevity.

Some of Al Fin's favourites that are on the list include Fight Aging, Ouroboros, and the Alliance for Aging Research.

Al Fin Longevity -- this blog -- finds itself on the top 50 list under the category of Longevity and Life Extension at #43.

As a side topic, I have noticed several healthcare training related blogs that provide wide ranges of lists of blogs for various topics. Some of these lists are quite useful. In fact, I would like to see a list of the top 100 list-making blogs. Wait -- what about a top 100 list of lists of top 100 list-making blogs? How about ..... Thwack!!

All righty then. My domestic android, Valerie, has just slapped me to bring me out of my list fugue. As Valerie points out, by the time you compiled the ultimate top 100 list of top 100 lists of lists of top 100 list-making blogs, the entire list would probably be obsolete. Please pardon me for the regression.

As scientific research pushes on, an extended lifespan becomes much more likely. The challenge will be not so much to keep living, but to combine the optimum mixture of enjoyable and important activities in order to fill one's life satisfactorily.

More important than improving the quantity of life is improving the quality of life. But doing both at the same time beats either one alone.

A Better Matrix for Artificial Tissues and Organs?

One of the challenges of creating artificial organs for replacement of human body parts is the need for a structural matrix to build the functional tissue around. Australian and Korean scientists have developed an interesting approach to the problem by pairing carbon nanotubes and DNA strands together, then treating them with calcium chloride solution to create cross-linking between the fibres.

The new concept uses DNA strands as a matrix; the strands completely “wrap” the scaffold-forming carbon nanotubes in the presence of an ionic liquid, networking them to form a gel. This gel can be spun: just as silk and synthetic fibers can be wet-spun for textiles, the gel can be made into very fine threads when injected into a special bath. The dried fibers have a porous, sponge-like structure and consist of a network of intertwined 50 nm-wide nanofibers. Soaking in a calcium chloride solution further cross-links the DNA, causing the fibers to become denser and more strongly connected.

These spongy fibers resemble the collagen fiber networks of the biological extracellular matrix. They can also be knotted, braided, or woven into textile-like structures. This results in materials that are as elastic as the softest natural tissues while simultaneously deriving great strength from the robust DNA links. An additional advantage is the electrical conductivity of the new material, which can thus also be used in electrodes for mechanical actuators, energy storage, and sensors. _Wiley

A similar matrix might be seeded with living cells to create tendons, cartilage, or more complex structures such as noses, ears, blood vessels, eyelids, lips, or as support reinforcement for hernia or breast surgeries etc. Reconstructive surgery and vascular surgery would create a demand for such living replacement parts immediately, should they prove safe and durable.

For more complex organs such as kidneys, livers, lungs, and hearts, more breakthroughs will be needed. For intermediate structures such as bladders, rectums, and other GI or GU segments, the jump from simple replacement parts may not be too difficult once the best ways for making the simpler parts are perfected.

Previously posted at Al Fin The Next Level

Tiny Nerve Stimulator Implants Use RFID Tech

These tiny implantable nerve stimulators are meant to stimulate peripheral nerves to treat chronic pain and other neurological disorders. But eventually, devices this small -- or smaller -- will fit near or within the brain, to deliver tiny currents of healing and eventually pleasure.

Like some cochlear implants and other medical devices, the implant is powered with radio-frequency transmission: radio waves transmitted by the external coil generate a magnetic field in the internal coil, which powers the electrodes. Adopting technologies from the rapidly advancing RFID world has allowed the researchers to further shrink the device. "Instead of trying to transfer energy from two coupled antennas to do telemetry, which is a common approach for medical devices, RFID is geared to have very small transponders, so you don't need a large coil," says Joseph Pancrazio, a program director at the National Institute for Neurological Disorders and Stroke, a government funding agency, in Bethesda, MD, that has given the company small business loans.

The research is still in a very early stage. Researchers have developed a prototype device, which they are testing in rats. The device can effectively stimulate peripheral nerves in rats, although it's not yet clear whether the electrical stimulation alleviates chronic pain. (Scientists assess chronic pain in rats by recording how much the animals eat; a rat in pain won't eat as much.)

Some scientists are skeptical that the device will be powerful enough to deliver a therapeutic level of stimulation. "The main limitation of any electronic device small enough to be injected into the body is that it must receive enough power to operate its circuitry and provide the required stimulation parameters," says Gerald Loeb, director of the Medical Device Development Facility at the University of Southern California, in Los Angeles. Loeb has also developed an injectable radio-powered microstimulator, which he says has encountered substantial limitations in range and power.

"We believe we can do it with less power," says Scott Armstrong, MicroTransponder's chief technical officer. However, he declined to give further details of the technology for proprietary reasons. _TechnologyReview

If not now, soon. It is quite clever of the researchers to use RFID technology for implantable nerve stimulators. Such an approach could be easily transferred to intracranial implants-without-antennas, as long as the power signal was able to safely penetrate the skull without damaging intervening tissues. Otherwise, antennas that are colour-matched to the person's hair could transmit the power signal to the implant. Advances in biocompatible materials will make such long-term implants viable.

Needless to say, technology that allows for miniaturisation of implants should also allow for simultaneous placement of multiple, strategically-placed implants that could communicate with each other, and coordinate for sophisticated neuro-stim routines.

Cross-posted at Al Fin

Restoring Lost Memories to Dementia Sufferers

When a person has a loved one with dementia, it is as if part of themselves is lost. Shared memories between pairs and groups of humans is a large part of what makes life satisfying and fun. When shared memories are lost, life's colours can fade. Researchers at MIT are attempting to understand the molecules of memory better, in order to restore lost memories to persons who suffer from dementia.

Having shed light on the mechanisms driving the progress of Alzheimer's disease, Tsai, who had come to MIT in 2006, wanted to figure out how to fight or even reverse some of the symptoms. She and postdoc Andre Fischer, now at the European Neuroscience Institute in Göttingen, Germany, knew of evidence from other studies that physical exercise and environmental enrichment--such as the addition of companions and toys--increases brain function in mice. So they decided to test what would happen if they tried this technique with their Alzheimer's-like mice.

In one experiment, they trained mice to find and remember a platform submerged within a murky pool. Then they induced the Alzheimer's-like effects. The mice swam aimlessly, unable to locate the spot. But when the researchers moved the mice to a more stimulating environment and then placed them back in the swimming pool, the rodents kicked directly to the platform. Those supposedly lost memories had returned.

....The results imply that restoring seemingly lost memories might also be possible in people. "Even in those patients that seem to lose their memory, we don't think the memory is really erased," she says. Tsai suspects that the massive neuronal die-off damages the brain's circuitry--the wiring that connects different regions. Rather than promoting neuron growth, she says, the new environment and the HDAC inhibitors strengthen synapses and dendrites, boosting connections between regions. In other words, they repair the circuits.

...."We're very hopeful," she says. "We may have something in the next few years that could be safe and beneficial enough to go into humans." Basic research may remain her first love, she adds. "But if my work can do something for the community or society, I would be so overjoyed." _TechnologyReview

We value most the things we can share.

If you don't have your mind, you have nothing. If you have your mind but not your health, at least you have your mind. Better to have your mind and your health, of course. Best of all, to be able to share good minds and good health with others of similar good fortune. A fulfilling life is a step by step proposition. Too often, the natural processes of life work against all of our efforts to create a fulfilling life. That is where we ask science to step in. It is not natural, what we are trying to do. But it is good.

Australian and American Researchers Team to Advance Regenerative Medicine Strategies

When humans can grow new organs to replace tired or damaged organs, we will transcend one of the reasons for too-early death: organ failure. Every advance in the field of regenerative medicine is a positive step toward that goal.

John Foster's Bio/Polymer Research Group at the University of NSW worked out in 2004 the correct wavelength of infra-red laser to seal sheets of the university's patented discovery, SurgiLux, over wounds.

Now Foster is teaming up with Stephen Badylak, pioneer of the extra-cellular matrix, at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. Badylak creates ECM from ground-up pig organs. It acts as a scaffolding material for wounds and can be absorbed by the body. Cells spontaneously regrow on it and adult stem cells are attracted from other parts of the body, developing into tissue similar to the original.

These scaffolds have helped more than one million people regrow cartilage, rebuild urethras and repair hernias.

Foster and Badylak hold high hopes for the marriage of their technologies now that Foster has been awarded aFulbright senior scholarship that will fund him for up to four months' work with Badylak's group from June next year. The aim is to develop the technology to support the surgical repair ofnerves. _Australian

Growing new cells and tissues in the proper mix of cell types with neurovascular and lymphatic support, will require precise methods and timing. Learning how to best attach the new cells, tissues, and organs to the rest of the body is a vital part of the regenerative picture.

Gamma Secretase Inhibitors: Meant for Alzheimer's but Also Helpful for Brain Trauma?

Georgetown University scientists have studied the use of gamma secretase inhibitors (GSIs) to prevent permanent brain injury after head trauma, in mice. GSIs prevent the formation of amyloid buildup in the brain, in order to prevent or mitigate the amyloid plaques of Alzheimer's disease.

Interestingly, amyloid also accumulates in the brains of persons with brain injuries -- even very young victims of head injury.

Researchers at Georgetown University Medical Center will publish their findings in an advance online publication of Nature Medicine.

They say the results suggest that this class of drugs could potentially do something no other drug has been able to do — prevent the long-term and continuing damage that often follows a serious injury to the brain.

That is because the agents, known as gamma secretase inhibitors, are designed to prevent buildup of amyloid, a toxic peptide found in the brain. This peptide clogs the brains of Alzheimer’s patients but it is also found in people who have died from traumatic brain injury, says the study’s lead author, neuroscientist Mark Burns, Ph.D, an assistant professor at GUMC.

“No one knows why it occurs, but abnormal amounts of amyloid plaque have been found during an autopsy in about a third of brain injury victims, some of whom were children who would ordinarily never have had these deposits,” says Burns. _PsychCentral

Amyloid deposits can begin building as soon as 1 day after injury -- demonstrating how dynamic a contribution amyloid may make to long term brain damage.

It is hoped that rapid diminution of amyloid deposits will lead to brain recovery in both Alzheimer's patients and in victims of traumatic brain injury. For mice, the treatment was successful in blocking permanent brain damage.

GSIs are currently investigational drugs. If they can demonstrate efficacy for both Alzheimer's and traumatic brain injury, clinicians can hope for a dual approval when the drugs are released.

Turbocharging Antibody Response to Cancer etc

The human immune system is a powerful deterrent to a wide range of diseases, including cancer. But it takes time to build an immunity to new diseases. Researchers at Scripps Research Institute have devised a synthetic adaptor that can generate an almost instant immune response to the protein target of one's choice.

Most vaccines - like those for measles or smallpox - prompt the immune system to build a standing army of antibodies against a virus or bacterium by injecting a deactivated version of the bug into the body.

But it can take weeks or months to build up immunity, and you have to catch people before they get infected. What's more, the approach doesn't always work - cancer and HIV vaccines have proved elusive.

So instead, Carlos Barbas and colleagues at the Scripps Research Institute in La Jolla, California, have developed dumb-bell shaped "adaptor" molecules that bind mouse antibodies to proteins on the surface of disease-causing agents, redirecting the antibodies' killing focus. In an earlier experiment they attached these molecules to a single kind of antibody in the lab, and injected these "retrofitted" antibodies into the mouse to kill tumour cells.

Now they have demonstrated that these synthetic molecules can bind many kinds of antibodies to cancer cells inside mice and reduce the size of implanted human tumours.

Four weeks after the molecules were injected, the colon tumours had shrunk by up to 90 per cent, and melanomas by 78 per cent (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0900147106). _NS

Even if this new immune therapy does not completely eradicate a tumour, by shrinking its size it gives the patient's medical team more time to chance upon the magic bullet treatment for that particular patient. Each person is different, so it is natural that a person's response to disease and therapy will be unique.

A Realistic Look at Obama's Stem Cell Order

President Obama's long anticipated and much heralded signing of new federal guidelines for the financing of embryonic stem cell research will help US scientists learn more of the mysteries of embryonic cell differentiation and manipulation. But in reality, the effect of the new rules will be far less significant for the future of regenerative medicine than most gullible news consumers will ever know.

.....the president’s support of embryonic stem cell research comes at a time when many advances have been made with other sorts of stem cells. The Japanese biologist Shinya Yamanaka found in 2007 that adult cells could be reprogrammed to an embryonic state with surprising ease. This technology “may eventually eclipse the embryonic stem cell lines for therapeutic as well as diagnostics applications,” Dr. Kriegstein said. For researchers, reprogramming an adult cell can be much more convenient, and there have never been any restrictions on working with adult stem cells.

For therapy, far off as that is, treating patients with their own cells would avoid the problem of immune rejection.

Members of Congress and advocates for fighting diseases have long spoken of human embryonic stem cell research as if it were a sure avenue to quick cures for intractable afflictions. Scientists have not publicly objected to such high-flown hopes, which have helped fuel new sources of grant money like the $3 billion initiative in California for stem cell research.

In private, however, many researchers have projected much more modest goals for embryonic stem cells. Their chief interest is to derive embryonic stem cell lines from patients with specific diseases, and by tracking the cells in the test tube to develop basic knowledge about how the disease develops.

Despite an F.D.A.-approved safety test of embryonic stem cells in spinal cord injury that the Geron Corporation began in January, many scientists believe that putting stem-cell-derived tissues into patients lies a long way off. Embryonic stem cells have their drawbacks. They cause tumors, and the adult cells derived from them may be rejected by the patient’s immune system. Furthermore, whatever disease process caused the patients’ tissue cells to die is likely to kill introduced cells as well. All these problems may be solvable, but so far none have been solved.

Restrictions on embryonic stem cell research originated with Congress, which, each year since in 1996, has forbidden the use of federal financing for any experiment in which a human embryo is destroyed. This includes the derivation of human stem cell lines from surplus fertility clinic embryos, first achieved by Dr. James Thomson of the University of Wisconsin in 1998.

President Clinton contemplated but never implemented a policy that would have allowed N.I.H.-financed researchers to study human embryonic stem cells derived by others. Research was able to begin only in August 2001, when President Bush, seeking a different way around the Congressional restriction, said researchers could use any lines established before that date.

Critics said the distinction between the Clinton and Bush policies lacked moral significance, given that each was intended to get around the Congressional ban, based on a religious and moral argument. The proposed Clinton policy amounted to: “Stealing is wrong, but it’s O.K. to use stolen property if someone else stole it.” The Bush policy was: “Stealing is wrong, but it’s O.K. to use stolen property if it was stolen before Aug. 9, 2001.”

Mr. Obama has put the proposed Clinton policy into effect, but Congressional restrictions remain. Researchers are still forbidden to use federal financing to derive new human embryonic stem cell lines. They will, however, be allowed to do research on new stem cell lines grown in a privately financed lab. _NYT

More research on embryonic stem cells will help scientists understand the intricate mechanisms of cell development. They will acquire a fabulous treasure trove of knowledge about many diseases -- both rare and less rare. The knowledge spinoffs from this research will stretch far beyond regenerative medicine (RM) to cancer treatments, life extension technologies other than RM, and a much deeper understanding of biological mechanisms in general.

But all of that would have occurred without that much celebrated penstroke yesterday. And it is undeniable that the flow of NIH funds to non-embryonic stem cell research has been a boon to technologies that are more immediately applicable to the everyday regenerative cell and tissue treatments of the future -- treatment using the patient's own cells.

Science under Obama is every bit as political as science under any other president -- and will probably only grow more political with time. Obama's promotion of carbon penalties (disguised as "cap and trade") are a politicised hyping of the pseudo science of catastrophic global warming from anthropogenic CO2. Obama's carbon hysteria-based political meddling in the energy industry is likely to make Americans far more miserable, leaving them with far less resources to deal with exigencies, than if he had done nothing at all.

So let's celebrate the abundant biological future that will eventually come to us via all the avenues of research being followed. And let us not fall for the hype surrounding the gilded age of Obamanation.

Taken from an earlier posting at Al Fin

More Engineered Stem Cell News

Toronto's Samuel Lunenfeld Research Institute at Mt. Sinai Hospital is the site of groundbreaking research on engineered stem cells.

"We hope that these stem cells will form the basis for treatment for many diseases and conditions that are currently considered incurable," said Dr. Nagy, Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Investigator at the McEwen Centre for Regenerative Medicine, and Canada Research Chair in Stem Cells and Regeneration. "This new method of generating stem cells does not require embryos as starting points and could be used to generate cells from many adult tissues such as a patient's own skin cells."

Dr. Nagy discovered a new method to create pluripotent stem cells (cells that can develop into most other cell types) without disrupting healthy genes. Dr. Nagy's method uses a novel wrapping procedure to deliver specific genes to reprogram cells into stem cells. Previous approaches required the use of viruses to deliver the required genes, a method that carries the risk of damaging the DNA. Dr. Nagy's method does not require viruses, and so overcomes a major hurdle for the future of safe, personalized stem cell therapies in humans.

"This research is a huge step forward on the path to new stem cell-based therapies and indicates that researchers at the Lunenfeld are at the leading edge of regenerative medicine," said Dr. Jim Woodgett, Director of Research for the Samuel Lunenfeld Research Institute of Mount Sinai Hospital. Regenerative medicine refers to enabling the human body to repair, replace, restore and regenerate its own damaged or diseased cells, tissues and organs. _PO

The new method avoids the risks of tumourogenesis that come with using viruses for reprogramming cells into stem cells. Various new and potent techniques of producing virtually any stem cell type from adult cells bring modern biomedicine ever closer to the ability to replace and / or rejuvenate virtually any tissues in the body -- using the person's own cells!

There is still much to be learned about the genetic switching mechanisms involved. Until we are certain that the re-programming techniques can truly provide safe, long-lived replacement cells for the various tissues of the body, we will need to continue experimenting with embryonic stem cell lines as well as with the re-programmed stem cells.

New Alzheimer's Disease Model Offers Hope for a New Array of Therapeutic Targets

Biomedical research is learning a great deal about how the brain works at the cellular level. Alzheimer's Disease, for example, is being seen more as an imbalance within normal cell processes -- like cancer. A better understanding of these processes should allow more precise targeting of drug research.

One of the mysteries of AD has been the normal function of the amyloid precursor protein (APP) which are concentrated at the points where neurons connect. Even though the sticky amyloid plaques which have been viewed as a hallmark sign of AD result from APP, it seems unlikely that APP exists simply to cause Alzheimer's disease. In their study, scientists from the Buck Institute and the CNRS (Centre Nationale de la Recherche Scientifique) show that APP binds to netrin-1, a protein that helps to guide nerves and their connections in the brain, as well as helping nerve cells to survive. When netrin-1 was given to mice that have a gene for Alzheimer's disease their symptoms were reversed, and the sticky amyloid was reduced. These results suggest that the long-held belief that AD is caused by brain cell damage inflicted by the amyloid plaques may be wrong; instead, it is beginning to appear that the disease stems from an imbalance between the normal making and breaking of connections in the brain, with netrin-1 supporting the connections and the amyloid breaking the connections -- both by binding to APP and activating normal cell programs. Not only did the netrin-1 binding to APP keep the nerve cells alive and connected, but it also shut down the production of the amyloid, all of which makes it an interesting potential therapeutic. _Scientistlive

In the past few decades, the therapeutic viewpoint toward Alzheimer's has paced the rapidly growing knowledge of the underlying mechanisms of the disease. Already we have gone through multiple generations of treatments, with several radically new treatments in the pipeline. If "netrin-1" or its analogues can be delivered to the proper brain regions, and can at least partially reverse both the histological and the clinical pathology in AD, we will not only have a better treatment, but we will have one more promising lead to follow.

New Stem Cell Hope For Parkinson's

Researchers in Bonn have developed a method of culturing an indefinite supply of replacement neural stem cells -- including the cells that fail in Parkinson's -- from a single embryonic source.

"The new cells, in contrast, serve as an inexhaustible source: they provide a supply of human neural cells over periods of months and years without demanding any recourse to supplementary embryonic stem cells", declares Professor Dr. Oliver Brüstle, head of the research team at the Institute for Reconstructive Neurobiology at Bonn University.

Using animal experiments, the researchers in Bonn provided direct proof that these artificially derived neural cells will also function. Transplanted into the brain of a mouse, these cells made contact with the recipient brain and were subsequently able both to send and receive signals. "This is the first direct evidence that neural cells derived from human stem cells are capable of synaptic integration in the brain", declares Dr. Philipp Koch, the original author of the study. The scientists in Bonn are now also hoping to exploit this inexhaustible cell source to study neurodegenerative diseases and possible active agents directly in human neural cells. _MNT

If scientists can prevent the rejection of donor stem cells, the pathway toward routine replacement of aging brain tissue is now being constructed. Adult induced pluripotent stem cells from the patient herself is the best means for preventing rejection of tissue and stem cell implants. But if embryonic cell and tissue banks are able to carry a large "on-demand" supply of suitable cells, they will be quite useful.

Clearly the promise of stem cell research applies to other diseases besides Parkinson's, and to other organs besides the brain.

The problem for the US -- where funding for the development of new embryonic stem cell lines is expected to be expanded -- is the overall economy. The new government appears not to understand how a market economy recovers from a recession -- a recession that was brought on by bad government policies to begin with. A helpful hint to Obama and Pelosi: get rid of those bad government policies! (CRA etc)

Interferon Makes Dormant Cells Vulnerable

Dormancy is an important protection mechanism of stem cells. First, it protects their genetic material from genetic alterations, which happen primarily during cell division. In addition, dormancy helps them escape attacks of many cytotoxins, which act only on dividing cells. _MNT

Many cancer stem cells are likewise dormant, which can protect them from chemotherapy. Waking these cancer stem cells up before chemotherapy is one way to kill more of them, and increasing chances for a remission. Interferon seems to wake stem cells up from a dormant state, and force them to divide. This makes them vulnerable to mutation and to cytotoxins.

Patients suffering from a type of blood cancer called chronic myelogenous leukemia who are treated with a drug called Gleevec almost always relapse after drug treatment has ended. Several patients were given interferon-alpha prior to the Gleevec treatment. Surprisingly, these patients experienced long relapse-free phases without any medication. "We believe that the leukemia stem cells were awakened by the interferon administration and, thus, were sensitized to elimination by Gleevec," Andreas Trumpp explains. _MNT

The other side of the story is that interferon makes normal stem cells vulnerable to cytotoxic agents, so that blood forming stem cells in the bone marrow will be killed by some chemotherapeutic agents such as 5-FU, if interferon is given first. This can cause severe anemia and death.

This knowledge can lead one to speculate about the effects of viral infections and natural interferon on stem cells in other locations, such as the brain. The constant infectious assault experienced in the tropics, for example, may lead to chronic depletion of stem cells with all of the failure of normal regeneration that such depletion implies.

Each scientific discovery becomes the trigger for new exploration. The contemporary human mind cannot keep up with the multiple ongoing chain reactions of knowledge, but computers should be of some help.

Skin Cells Programmed to Become Heart Cells

Using techniques of induced pluripotent stem cell conversion, scientists at the University of Wisconsin created heart cells out of skin cells. The idea is to take a person with heart failure, make functioning replacement heart cells from abundant skin cells, and give the person what is in essence a new heart.

"This is the first demonstration that human induced cells can form different types of heart cells in a dish," said study co-author Tim Kamp, a University of Wisconsin cell biologist.

The latest findings, published Thursday in Circulation Research, suggests that failing hearts might be mended.

"We didn't know whether they could form heart cells efficiently," said Kamp. "But they successfully formed heart cells with all the electrical and organizational properties we'd expect."

In the last few years, induced pluripotency has been hailed as an uncontroversial alternative to embryonic stem cells, production of which requires the destruction of embryos.

Reprogramming flakes of skin would be a far easier alternative. _Wired