2. Kidneys grown from stem cells
• Kidneys grown from stem cells from amniotic
fluid and animal foetal cells
• Depends on patient’s own amniotic fluid being
saved at birth
• No risk or rejection
4. SENS 2010 Research Report
• LysoSENS
• A2E synthesis ability
• Modified versions of eight microbial hyrolases
• Developed HPLC assay
• AptoSENS and ReplenSENS
– Constructed T-cell “scubber”
• OncoSENS
– Method to determine gene-specific DNA mythalation patterns in single cells
• AmyloSENS
– New project gearing up in Dublin and University of Texas in Huston
• MitoSENS
– Obviating mitochondrial DNA deletions
– Tranisent expression of mitochondrially-encode proteins
8. Neurons produced from human skin
cells
• Use of 4 proteins can convert skin cells to
neurons in 4-5 weeks
– Stanford University School of Medicine
– No need to create pluripotent stem cell first
• Could news because some pluripotent techniques
result in rejection
– Work can be used to study neurological function
and diseases more easily in lab
12. More Stem Cell News
• Means to grow stem cells in suspension
– Also work of growing spheres of stem cells
• New growth factor stimulates expansion and
regeneration of blood forming stem cells
• Pluripotent stem cells from blood
• 100x more efficient programming of stem cells
13. Medical TricorderXPrize
• Qualcomm and Xprize are offering $10 million
for a medical tricorder
– Mobile solutions diagnosing many common
conditions as well as medical certified doctors
– Depends on advances in sensing, microfluidics,
computation
• Chip based radars are relevant to scanning
• Small blood samples and microfluidics for in field blood
work
14. Extreme exercise for longer life?
• Tour of France cyclist live on average 8 years
longer
• A little damage or stress increases
mitochondrial oxygen consumption
• Reactive oxygen species (ROS) seems to
increase stress resistance and longevity
– Contrary to the oxidation (and anti-oxidant)
notions of aging
– Anti-oxidants can actually interfere with ROS
Editor's Notes
Creating an organ using a patient's own stem cells solves the problem of having to use powerful immunosuppressant drugs to stop the body rejecting a another person's kidney.Professor Davies said the technology could be ready for use on humans in around 10 years. http://nextbigfuture.com/2011/04/kidneys-grown-from-stem-cells-that-were.html
Some SENS news but first a bit of review of SENS, Strategiens for Eniginneered Negligible Senesence. The basic idea is that there is a small set of things that go wrong as bodies age. Together that small set of things causes the cumulative damage of aging. The SENS idea is to slow, clean up and eventually reverse each of these effects thus effectively halting and eventually reversing aging. SENS a regenerative medicine program to cure each of these aging effects. There are seven major aging aspects and corresponding areas of research and development. RepliSENShttp://www.sens.org/sens-research/research-themes/replenisensReplacing lost cells.Cell depletion is the loss of cells without equivalent replacement. It happens in some of our most important tissues as we age. The brain and heart are particularly affected but it can also affect our skeletal muscles.The SolutionCell depletion can be fixed in two main ways: by stimulating the division of existing cells, or by directly introducing new ones. Cell division is naturally stimulated in some muscles by exercise (although most of the increased tissue volume and strength is a result of the increased size of the exercised cells rather than increased number), and can be artificially stimulated through the introduction (e.g. by injection) of growth factors that stimulate cell division; this works well in muscle, and animal studies suggest that it may also work in the thymus, an organ with an important role in the immune system that progressively shrinks with age.OncoSENS - Making cancerous mutations harmless.http://www.sens.org/sens-research/research-themes/oncosensThe Solution: WILTThis means that we don't actually need to fix chromosomal mutations at all in order to stop them from killing us: all we need to do is develop a really, really good cure for cancer. WILT (which was the topic of the third SENS Roundtable) is an acronym for Whole-body Interdiction of Lengthening of Telomeres.The idea is based on that DNA require teleomeres to keep from unraveling and since a bit of telemores and is lost in each cell reproduction and cancer cells reproduce quicker than normal. If you had the means to suppress the mechanism used to create more telemorase then cancer cells should die quickly. Normal cells can go up to a decade without running dangerously low on telomerase. An injection once a decade of stem cells would keep telemorase for normal cells topped off.MitoSENShttp://www.sens.org/sens-research/research-themes/mitosensThe mitochondrion is a machine within the cell that acts as the "power plant" of the cell. Mitochondria take oxygen and chemically combine it with energy-rich nutrients from our food, to make carbon dioxide and water (which we exhale) and ATP, the "energy currency" of the cell.unlike any other part of the cell, mitochondria have their own DNA (mtDNA), separate from the nucleus. Being at the site of cellular respiration, the mtDNA is vulnerable to its reactive by-products. Worse yet, the mitochondria's capacity for repairing DNA damage is much more limited than that of the nucleus. Thus we need a different system to combat the inevitable accumulation of such mutations.Solution – putting backup copies of the dozen or so mitochondrion only genes into cell nucleuses. The cells that most severely accumulate mutant mitochondria are non-dividing ones like muscle fibres and neurons. This is a shame, because it means we will need really good gene therapy to get these supplementary genes into the cells that need them. But gene therapy is improving all the time - and also, even if we could only fix half the affected cells, we'd still be achieving a rejuvenation, which we could progressively improve upon with new gene therapy advances.ApoptoSENS – Removing cells the body tries but fails to kill.http://www.sens.org/sens-research/research-themes/apoptosensThere are three main classes of cells that sometimes acquire a metabolic state that is damaging to their neighbours, and that accumulate in the body during aging:Visceral fat cells – accumulates around organs of the gut decrease response to nutrients and tending to type II diabetesSenescent cells – cells that have lost reproductive capability and have abnormal metabolism Immune cells – no longer effective immune cells block the body producing more potent new immune cellsSolution: Find something that will cause only the unwanted cells to die OR stimulate immune system to more effectively kill such cells.GlycoSENS – Breaking extracellular cross-linkshttp://www.sens.org/sens-research/research-themes/glycosensProtein glycation or crosslinking of proteins that should be free moving. This influences skin and articery elasticity, transparency of lens of eye, ligament tensile strength to name a few. Solution – cross links have an unusual chemical structure not found in rest of body. This can possibly be targeted by chemicals that break up cross links. Such a molecule has been found and seems to work in early tests.It is the drug ALT-711 (alagebrium). This molecule doesn’t work on all types of crosslinks but appears to be fairly effective on several important types.AmyloSENS – Destroying junk between cellshttp://www.sens.org/sens-research/research-themes/lycosensExtracellular junk is aggregates of stuff that do not have any function and should ideally have been cleared out of the body, but have proven resistant to destruction. Extracellular junk is different from extracellular cross-linking - it refers only to substances that do not have any function, not even a biophysical one.Most of this junk is termed "amyloid" of one variety or another. You may have heard of one form of amyloid - Abeta, the stifling, web-like material that forms plaques in the brains of patients with Alzheimer's disease, and also (more slowly) in everyone else's.The Solution – possibly vaccinations to stimulate immune system to clear out this junk. In practice the approaches tried so far have had to many side effects. No approaches are to introduce a tailored macrophage with an appetite only for some of these types of extracellular junk.LysoSENS – Destroying junk inside cellsThe aging body also accumulates junk within cells that is not eliminated as well. Cells have a lot of reasons to break down big molecules and structures into their component parts, and a lot of ways to do so. Unfortunately, one of the main reasons to break things down is because they have been chemically modified so that they no longer work, and sometimes these chemical modifications create structures that are so weird that none of the cell's degradation machinery works on them.This situation is very rare, but in the long run these modified chemicals add up. Ultimately the chemicals end up in the lysosome, a special vessel that contains the most powerful degradation machinery in the cell. If something can't be broken down there, it just stays there forever. This doesn't matter in cells that divide regularly, because division dilutes the junk enough that it remains at harmlessly low levels, but non-dividing cells gradually fill up with this stuff, making them dysfunctional. The heart, the back of the eye, some nerve cells (especially motor neurons) and, most of all, white blood cells trapped within the artery wall all suffer from this.The SolutionThe most promising approach is to enable cells to break the junk down so that they don't fill up after all. This can be accomplished by equipping the lysosome with new enzymes that can degrade the relevant material.
2010 Research report @ http://www.sens.org/files/pdf/SENSF_2010_Year_End_v3.1.pdfLysoSENS2010 milestones. The creation of an internal A2E synthesis capability enabled efficient target enzyme evaluation. Our successful development of a protein purification protocol resulted in the isolation of an active, A2E-degrading enzyme.The year ahead. We will express and purify additional candidate enzymes for both macular degeneration and atherosclerosis projects; establish activity of these additional enzymes in vitro; perform cell-uptake studies, in RPE cells for A2E and in macrophages for 7-ketocholesterol (7KC); and perform initial toxicity studies.LysoSENSLocation. Rice University, Houston, Texas2010 milestones. We have designed and synthesised modified versions of eight microbial hydrolases, the expressions of which are upregulated by 7KC; developed an HPLC assay; and expressed proteins for target candidates.The year ahead. We will develop further expression testing for cloned proteins and conduct in vitro activation testing.ApoptoSENS and RepleniSENS Location. University of Arizona, Tucson, Arizona2010 milestones. We have constructed a prototype T-cell “scrubber” and confirmed that it reduces the abundance of dysfunctional immune cells; prepared suitably infected mice and verified their immune status; and applied permutations of immunorejuvenationtherapies.The year ahead. We will analyse the data collected and publish results.In collaboration with students at the State University of New York at Plattsburgh, we have also made significant progress in improving the A2E-degrading capacity of versatile peroxidase (an extant enzyme previously identified by screening a commercial library) through chimeric addition of an additional moiety. MitoSENS 2010 milestones. SENS hasestablished an in-house MitoSENS program, based on previous, funded work in the INSERM laboratory of Dr Corral-Debrinski.The year ahead. We will transiently express mitochondrially-encoded proteins (ND1, ND4, ATP6) from provided expression plasmids; confirm localization to mitochondria by immunofluorescence; design and synthesize “nuclear” cytochrome B followed by similar expression and localization; demonstrate Complex III functional rescue with nuclear expression of cytochrome B.
A team led by developmental biologist Professor Christophe Marcelle has nailed the mechanism that causes stem cells in the embryo to differentiate into specialised cells that form the skeletal muscles of animals’ bodies. The scientists published their results in the British journal Naturehttp://www.nature.com/nature/journal/vaop/ncurrent/abs/nature09970.html“How dynamic signalling and extensive tissue rearrangements interact to generate complex patterns and shapes during embryogenesis is poorly understood. Here we characterize the signalling events taking place during early morphogenesis of chick skeletal muscles.”Professor Marcelle’s team analysed the differentiation of muscle stem cells in chicken embryos. The mechanisms in birds are identical to those in mammals, so the chick is a good model species for understanding the mechanisms in humans, says team member and the paper’s lead author, Anne Rios.The scientists investigated the effect of a known signalling pathway called NOTCH on muscle differentiation. They found that differentiation of stem cells to muscle was initiated when NOTCH signalling proteins touched some of the cells. These proteins were carried by passing cells migrating from a different tissue–the neural crest–the progenitor tissue of sensory nerve cells. Muscle formation in the target stem cells occurred only when the NOTCH pathway was triggered briefly by the migrating neural crest cells.“This kiss-and-run activation of a pathway is a completely novel mechanism of stem cell specification which explains why only some stem cells adopt a muscle cell fate,” Ms Rios said.Professor Marcelle said that more than 2 per cent of the population was affected by muscle dysfunction. “Muscle frailty in aging and disease imposes a huge economic burden, so it is critical to explore novel avenues of research that could lead to new treatments,” he said.He said the team would now focus on unraveling the mechanisms of embryonic muscle cell differentiation at the molecular level as a necessary step to regulating regeneration of the muscles in human patients.
http://www.news.cornell.edu/stories/May11/stroockDermal.htmlTop left, a tissue scaffold with pores visible. Clockwise, schematic diagrams showing cross-sections microstructured tissue templates.The biomaterials are composed of experimental tissue scaffolds that are about the size of a dime and have the consistency of tofu. They are made of a material called type 1 collagen, which is a well-regulated biomaterial used often in surgeries and other biomedical applications. The templates were fabricated with tools at the Cornell NanoScale Science and Technology Facility to contain networks of microchannels that promote and direct growth of healthy tissue into wound sites.The grafts promote the growth of a vascular system -- the network of vessels that carry blood and circulate fluid through the body -- to the wounded area by providing a template for growth of both the tissue (dermis, the deepest layer of skin), and the vessels. Type I collagen is biocompatible and contains no living cells itself, reducing concerns about immune system response and rejection of the template.Dermal templates are not new; the Johnson and Johnson product Integra, for example, is widely used for burns and other deep wounds, Spector said, but it falls short in its ability to encourage growth of healthy tissue because it lacks the microchannels designed by the Cornell researchers.
http://www.physorg.com/news/2011-05-biomaterial-mimics-human-tissue.html#shareOptical images of polyethylene glycol scaffolds expanding in response to stretching.A new biomaterial designed for repairing damaged human tissue doesn’t wrinkle up when it is stretched. The invention from nanoengineers at the University of California, San Diego marks a significant breakthrough in tissue engineering because it more closely mimics the properties of native human tissue.This biofabrication technique uses light, precisely controlled mirrors and a computer projection system -- shined on a solution of new cells and polymers -- to build three-dimensional scaffolds with well-defined patterns of any shape for tissue engineering.Shape turned out to be essential to the new material’s mechanical property. While most engineered tissue is layered in scaffolds that take the shape of circular or square holes, Chen’s team created two new shapes called “reentrant honeycomb” and “cut missing rib.”A single layer would not be thick enough to repair a heart wall or skin tissue, for example. The next phase of research will involve working with the Department of Bioengineering at the Jacobs School of Engineering to make tissue grafts to repair damaged blood vessels.Both shapes exhibit the property of negative Poisson’s ratio (i.e. not wrinkling when stretched) and maintain this property whether the tissue patch has one or multiple layers.
One wonders if we could produce artificial brain boxes with such technology. I don’t see a good reason why not.http://www.physorg.com/news/2011-05-scientists-human-skin-cells-neurons.html
https://www.opencures.org/OpenCures wishes to do knowledge management of all anti-aging related research, practices and practitioners and make it openly available. Open Cures, an open volunteer initiative that aims to speed the advent of biotechnologies that can slow down or repair aspects of the biological damage of aging and thus extend healthy human life. Our primary long-term goal is to bring together (a) promising but undeveloped biotechnologies of longevity and (b) the developers who can bring them to the clinic. The first steps toward a future of biotechnology development supported and enhanced by an eager and open community can be taken by volunteers: Help to publish, explain, and publicize demonstrated longevity biotechnology. Build relationships with the open biotech, medical tourism, and overseas development communities. Spur the clinical development of longevity medicine where no such development would otherwise have occurred. With many helping hands, the roadblocks of regulation that slow and block medical development can be made irrelevant. We live in the midst of a revolution in biotechnology, a time of rapid and amazing progress; but this revolution is less than ideal when it comes to producing results in the clinic. Thanks to legal strictures placed upon medical development by government bodies - such as the Food and Drug Administration in the US - a range of biotechnologies with the potential to extend healthy life have been demonstrated in the laboratory but remain undeveloped for human use. At the same time, we live in a shrinking world of diverse regions and cultures with different legal rules, all increasingly linked by the Internet, cheap air travel, and automated translation tools. Some regions, such as countries in the Asia-Pacific region, permit more freedom for clinical development of new medical technologies. We see this in the stem cell therapies, available for some years outside the US, while being forbidden within US borders. The situation for aging and longevity is far worse than for stem cells, however. The FDA will not approve treatments for aging, and there is no established road map or initiative underway with the hope of changing that stance.
http://www.popsci.com/science/article/2011-05/stem-cell-therapy-humans-horse-tested-vet-approvedSimple Treatment of extacting stem cells, growing them and then injecting* Take bone-marrow samples from 61 horses suffering soft-tissue injuries, extracted the stem cells, and allowed them to proliferate in the lab.* take the concentrated cell formula and injected it into the horses’ injured tendons* Nearly two years after treatment, 85 percent of these horses, all of which had been failed by previous rehab programs, were healed.
http://www.nature.com/nbt/journal/vaop/ncurrent/abs/nbt.1616.htmlPreviously stem cells were most commonly grown in single layers. This paper from an Israeli research center outlines a method for growth in suspension. This greatly increases volume/time of stem cells.It was thought that propagation of hESCs in a suspension (a mixture in which fine particles are suspended in a fluid where they are supported by buoyancy) was impossible because under these conditions, the cells would stop multiplying and instead undergo uncontrolled ripening into various types of cells.But the Hadassah researchers developed unique conditions that made it possible for the cells to multiply significantly in suspension without differentiating into specific cell types. By changing the conditions of the culture, they showed that they could control the ripening of hESC clusters in suspension into neural spheres. Thus instead of being grown on beds in one layer, the stem cells could be cultivated in large vats with precise, computerized monitoring of growth conditions.http://www.eurekalert.org/pub_releases/2010-03/dumc-ngf031810.phpadding pleiotrophin, a naturally-occurring growth factor, stimulated a ten-fold expansion of stem cells taken from the bone marrow of a mouse. They also found that pleiotrophin increased the numbers of human cord blood stem cells in culture that were capable of engraftment in immune-deficient mice. When they injected pleiotrophin into mice that had received bone marrow-suppressive radiation, they observed a 10-fold increase in bone marrow stem cells compared to untreated mice. "These results confirmed that pleiotrophin induces stem cell regeneration following injury,”http://www.cell.com/cell-stem-cell/fulltext/S1934-5909%2810%2900284-5http://www.bbsrc.ac.uk/news/health/2011/110331-pr-stem-cells-3d-experiments.aspxOur study demonstrates that peripheral blood can be utilized as an easily accessible source of patient tissue for reprogramming without the need to extensively maintain cell cultures prior to reprogramming experiments. This is an important step to make the iPSC technology more broadly applicableThe new studies accomplished the reprogramming feat by using viruses to deliver a four-gene cocktail that reverts the cells to a naïve state in which any developmental path is open. In theory at least, these induced pluripotent stem cells could go on to form neurons in the brain, muscle cells in the leg or beating heart cells. Scientists’ manipulations turned the stem cells in the new studies into several types of mature blood cells, including infection-fighting T cells. What’s more, all the groups showed that a batch of the stem cells implanted into mice developed into the three main types of progenitor cells found in human embryos. In embryos, these progenitor cells give rise to different tissues. 100x more efficient programminghttp://nextbigfuture.com/2011/04/new-way-to-make-reprogrammed-stem-cells.htmlBefore this procedure, which uses microRNAs instead of the four key transcription factor genes, for every 100,000 adult cells re-programmed, researchers were able to get a small handful of iPSCs, usually less than 20. Using the microRNA-mediated method, they have been able to generate approximately 10,000 induced pluripotent stem cells from every 100,000 adult human cells that they start with. MicroRNAs (miRNAs) are short RNA molecules that bind to complementary sequences on messenger RNAs to silence gene expression.
Hormesis is the process by which a little damage or stress to our biology can lead to a longer life span, as it wakes up the repair mechanisms and makes them do a better job than they otherwise would - a net gain in resiliency.This review aims to summarize published evidence that several longevity-promoting interventions may converge by causing an activation of mitochondrial oxygen consumption to promote increased formation of reactive oxygen species (ROS). These serve as molecular signals to exert downstream effects to ultimately induce endogenous defense mechanisms culminating in increased stress resistance and longevity, an adaptive response more specifically named mitochondrial hormesis or mitohormesis.http://www.ncbi.nlm.nih.gov/pubmed/21619928