Stem Cell Therapy: Non-Surgical Treatment for Neck Pain Whiplash
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Stem Cell Therapy: Non-Surgical Treatment for Neck Pain & Whiplash - Video

The development of human embryonic stem cells, which have the ability to form any cell in the body, may enable us to repair tissues damaged by injury or disease. Initially, these cells could only be obtained through methods that some deemed ethically unacceptable, but researchers eventually developed a combination of genes that could reprogram most cells into an embryonic-like state. That worked great for studies, but wasn't going to work for medical uses, since one of the genes involved has been associated with cancer.

Researchers have since been focusing on whittling down the requirements needed for getting a cell to behave like a stem cell. Now, researchers have figured out a radically simplified process: expose the cells to acidic conditions, then put them in conditions that stem cells grow well in. After a week, it's possible to direct these cells into a state that's even more flexible than embryonic stem cells.

The catalyst for this work is rather unusual. The researchers were motivated by something that works in plants: expose individual plant cells to acidic conditions, grow them in hormones that normally direct plant development, and you can get a whole plant back out. But we're talking about plants here, which evolved with multicellularity and with specialized tissues in a lineage that's completely separate from that of animals. So there's absolutely no reason to suspect that animal cells would react in a similar way to acid treatmentand a number of reasons to expect they wouldn't.

And yet the researchers went ahead and tried anyway. And, amazingly, it worked.

The treatments weren't especially harshonly a half-hour in a pH of 5.45.8. Afterward, the cells were placed in the same culture medium that stem cells are grown in. Many of the cells died, and the ones that were left didn't proliferate like stem cells do. But, over the course of a week, the surviving cells began to activate the genes that are normally expressed by stem cells. This was initially tried with precursors to blood cells, but it turned out to work with a huge variety of tissues: brain, skin, muscle, fat, bone marrow, lung, and liver (all of them obtained from micethis hasn't been tried with human cells yet).

While these cells didn't divide like stem cells, they did behave like them. Injecting them into embryos showed that they were incorporated into every tissue in the body, meaning they had the potential to form any cell. That suggests they are a distinct class of cell from the other ones we're aware of (the researchers call them STAP cells).

But, if they don't grow in culture, it's hard to use or study them. So, the authors tried various combinations of hormones and growth factors that stem cells like. One combination got some of the STAP cells to grow, after which they behaved very much like embryonic stem cells. But a second combination of growth factors got the cells to contribute to non-embryonic tissues, like the placenta, as well. So, in this sense, they seem to be even more flexible than embryonic stem cells, and seem more akin to one of the first cells formed after fertilization.

The people behind this development have done a tremendous amount of work, so much that it was spread across two papers. Still, like many good results, it raises lots of other questions. Many cells in our bodies get exposed to acidic conditions every daywhy do those manage to stably maintain their identity? A related question is what goes on at a molecular level inside the cell after acid treatment. Understanding that will help us learn more about the stem cell fate itself.

And then there are the practical questions. How close are these STAP cells to an actual embryonic cell, in terms of the state of its DNA and gene expression? And, if there are differences, are they significant enough to prevent these cells from being used in safe and efficient medical treatments?

January 30, 2014. DOI: 10.1038/nature12968, 10.1038/nature12969 (About DOIs).

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Acid bath turns cells from any tissue into stem cells

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29-Jan-2014

Contact: Shaun Mason smason@mednet.ucla.edu 310-206-2805 University of California - Los Angeles

Scientists from UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research were today awarded grants totaling more than $3.5 million by California's stem cell agency for their ongoing efforts to advance revolutionary stem cell science in medicine.

Recipients of the awards from the California Institute of Renerative Medicine (CIRM) included Lili Yang ($614,400), who researches how stem cells become rare immune cells; Denis Evseenko ($1,146,468), who is studying the biological niche in which stem cells grow into cartilage; Thomas Otis and Bennet Novitch ($1,148,758), who are using new techniques to study communication between nerve and muscle cells in spinal muscular atrophy; and Samantha Butler ($598,367), who is investigating the molecular elements that drive stem cells to become the neurons in charge of our sense of touch.

"These basic biology grants form the foundation of the revolutionary advances we are seeing in stem cell science," said Dr. Owen Witte, professor and director of the Broad Stem Cell Research Center. "Every cellular therapy that reaches patients must begin in the laboratory with ideas and experiments that will lead us to revolutionize medicine and ultimately improve human life. That makes these awards invaluable to our research effort."

The awards are part of CIRM's Basic Biology V grant program, which fosters cutting-edge research on significant unresolved issues in human stem cell biology, with a focus on unravelling the key mechanisms that determine how stem cells decide which cells they will become. By learning how such mechanisms work, scientists can develop therapies that drive stem cells to regenerate or replace damaged or diseased tissue.

Lili Yang: Tracking special immune cells

The various cells that make up human blood all arise from hematopoietic stem cells. These include special white blood cells called T cells, the "foot soldiers" of the immune system that attack bacteria, viruses and other disease-causing invaders. Among these T cells is a smaller group, a kind of "special forces" unit known as invariant natural killer T cells, or iNKT cells, which have a remarkable capacity to mount immediate and powerful responses to disease when activated and are believed to be important to the immune system's regulation of infections, allergies, cancer and autoimmune diseases such as Type I diabetes and multiple sclerosis.

The iNKT cells develop in small numbers in the blood generally accounting for less than 1 percent of blood cells but can differ greatly in numbers among individuals. Very little is known about how blood stem cells produce iNKT cells.

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Stem cell agency's grants to UCLA help set stage for revolutionary medicine

January 28, 2014

Brett Smith for redOrbit.com Your Universe Online

While a Chinese cream may not have cured George Costanzas baldness in a classic Seinfeld episode, stem cell research from scientists at the University of Pennsylvania has shown the potential for regenerating hair follicles which could lead to relief for hair-challenged men everywhere.

According to a new report published in the journal Nature Communications, the Pennsylvania researchers have developed a groundbreaking method for converting adult cells into epithelial stem cells (EpSCs). Similar previous efforts have failed to generate an adequate number of hair-follicle-generating stem cells.

In the study, epithelial stem cells were inserted into immunocompromised mice. The stem cells regenerated the various cell types for human skin and hair follicles, and provided structurally identifiable hair shafts, raising the possibility of hair regeneration in humans.

The study team began with human skin cells referred to as dermal fibroblasts. By incorporating three genes, they modified those cells into induced pluripotent stem cells (iPSCs), which have the capacity to differentiate into any cell types in the human body. Next, they modified the iPS cells into epithelial stem cells, commonly located at the base of hair follicles.

Starting with procedures other research groups had worked out to transfer iPSCs into skin cells, Xus team figured out that by carefully manipulating the timing of the cell growth factors, they could drive the iPSCs to produce large quantities of epithelial stem cells. This method was able to turn more than 25 percent of the iPSCs into epithelial stem cells within 18 days. Those cells were then purified based on the proteins they showed on their surfaces.

Comparison of the engineered cells with epithelial stem tissue obtained from hair follicles revealed the team succeeded in making the cells they set out to produce. After mixing all those cells with mouse follicular inductive dermal cells and attaching them onto the pores and skin of immunodeficient mice, the team was able to produce efficient outer layers of human skin tissue and follicles structurally similar to those generated by human hair.

This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles, said study author Dr. Xiaowei George Xu, associate professor of pathology and laboratory medicine and dermatology at the university. He added that these cells could be used for healing, cosmetics and hair regeneration.

Xu cautioned that iPSC-derived epithelial stem cells are not yet ready for human subjects.

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Are Stem Cells The Cure To Baldness?

28 January 2014-Scientists from the Genome Institute of Singapore (GIS) in A*STAR have developed a novel method of directing human pluripotent stem cells (hPSCs) into highly pure populations of endoderm[1], a valuable cell type that gives rise to organs including the liver and pancreas.

These cells are highly sought-after for therapeutic and biotechnological purposes, but have been historically difficult to attain from hPSCs. The ability to generate pure endoderm at higher yields from hPSCs is a key and important step towards the use of stem cells in clinical applications.

The discovery, published in the prestigious scientific journal Cell Stem Cell in January 2014, was led by Dr Bing Lim, Senior Group Leader and Associate Director of Cancer Stem Cell Biology at the GIS, Dr Lay Teng Ang, a postdoctoral fellow from Dr Lims lab, and Kyle Loh, a graduate student at Stanford University School of Medicine.

hPSCs are stem cells that can generate over 200 distinct cell types in the human body. They respond to multiple external protein instructions to differentiate into other cell types. Therefore, generating one single cell type from hPSCs, and a pure population of that given cell type, is delicate as hPSCs have a tendency to also form other types of cells.

Employing a highly systematic and novel approach, the group screened for proteins and chemicals that promote the formation of a single desired cell type, and concurrently block induction of unwanted cell types. This strategy uncovered a combination of triggers that could drive hPSCs towards pure populations of endoderm. The valuable cells produced and the insights gained from this work have brought stem cells one step closer to clinical translation and furthered basic research into the understanding of how cell fates are specified during stem cell differentiation.

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:: 28, Jan 2014 :: SINGAPORE SCIENTISTS SUCCEED IN MANIPULATING STEM CELLS INTO LIVER AND PANCREAS PRECURSOR CELLS

11 hours ago by Katarina Sternudd

Scientists at Karolinska Institutet and Gurdon Institute in Cambridge, United Kingdom have identified a novel mechanism that allows pluripotent stem cells to maintain their genome in an unpacked state, and thereby maintain their unique property to give raise to all types of specialized cells in the body. The findings are presented in the journal Nature.

Embryonic stem cells and induced pluripotent stem cells have the capacity to give rise to all cell types present in the adult body. To maintain this immature state, genes that are turned on in specialized cells must remain inactive in pluripotent cells, but ready to be quickly activated upon maturation into, for example, a cell in the skin or liver. The genome of a cell is packed in the nucleus, in a structure called chromatin. If the chromatin packing is tight (condensed), activatory molecules cannot access parts of the genome that control the activation of genes. Thus, for a certain gene to be activated, the chromatin structure must be unpacked (decondensation).

Pluripotent stem cells are unique in that their genome is partially unpacked (chromatin decondensation), when compared to specialized cells, to allow rapid activation of differentiation genes upon a given stimuli. In this published study, an international team, lead by Professor Tony Kouzarides, at the Gurdon Institute, University of Cambridge, identified a specific enzymatic activity, called citrullination, that contributes to decondensed chromatin state in pluripotent cells.

"The genome (DNA) is highly negatively charged and is associated in the chromatin structure with proteins called histones, which are highly positively charged. We found that in pluripotent cells, citrullination reduces the charge of some histones, weakening their association with the genome and contributing to decondensation", says Gonalo Castelo-Branco, principal investigator at Karolinska Institutet and co-first author in the study with Maria Christophorou of the Gurdon Institute.

Gonalo Castelo-Branco's research group at Karolinska Institutet is now investigating roles for citrullination in other immature cells, such as oligodendrocyte precursors in the brain, which participate in myelin regeneration in multiple sclerosis, MS.

Research in this study was funded by grants from Cancer Research UK, the Swedish Research Council, EMBO, European Union 7th Framework Programme (FP7) Marie Curie Actions, among others grants. Gonalo Castelo-Branco implemented parts of the study at the Gurdon Institute, where he was previously a researcher, and at Karolinska Institutet. Among the study authors is also professor John Gurdon, laureate of the Nobel Prize in Physiology or Medicine 2012. Apart from Sweden and United Kingdom, scientists from Denmark, Brasil and USA participated in the study.

Explore further: New method increases supply of embryonic stem cells

More information: "Citrullination regulates pluripotency and histone H1 binding to chromatin." Maria A. Christophorou, Gonalo Castelo-Branco, Richard P. Halley-Stott, et al. Nature (2014) DOI: 10.1038/nature12942. Received 06 September 2012 Accepted 06 December 2013 Published online 26 January 2014

Journal reference: Nature

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New mechanism for genome unpacking in stem cells

Jan. 23, 2014 Stem cells can turn into heart cells, skin cells can mutate to cancer cells; even cells of the same tissue type exhibit small heterogeneities. Scientists use single-cell analyses to investigate these heterogeneities. But the method is still laborious and considerable inaccuracies conceal smaller effects. Scientists at the Helmholtz Zentrum Muenchen, at the Technische Unitversitaet Muenchen and the University of Virginia (USA) have now found a way to simplify and improve the analysis by mathematical methods.

Each cell in our body is unique. Even cells of the same tissue type that look identical under the microscope differ slightly from each other. To understand how a heart cell can develop from a stem cell, why one beta-cell produces insulin and the other does not, or why a normal tissue cell suddenly mutates to a cancer cell, scientists have been targeting the activities of ribonucleic acid, RNA.

Proteins are constantly being assembled and disassembled in the cell. RNA molecules read blueprints for proteins from the DNA and initiate their production. In the last few years scientists around the world have developed sequencing methods that are capable of detecting all active RNA molecules within a single cell at a certain time.

At the end of December 2013 the journal Nature Methods declared single-cell sequencing the "Method of the Year." However, analysis of individual cells is extremely complex, and the handling of the cells generates errors and inaccuracies. Smaller differences in gene regulation can be overwhelmed by the statistical "noise."

Scientists led by Professor Fabian Theis, Chair of Mathematical modeling of biological systems at the Technische Universitaet Muenchen and director of the Institute of Computational Biology at the Helmholtz Zentrum Muenchen, have now found a way to considerably improve single-cell analysis by applying methods of mathematical statistics.

Instead of just one cell, they took 16-80 samples with ten cells each. "A sample of ten cells is much easier to handle," says Professor Theis. "With ten times the amount of cell material, the influences of ambient conditions can be markedly suppressed." However, cells with different properties are then distributed randomly on the samples. Therefore Theis's collaborator Christiane Fuchs developed statistical methods to still identify the single-cell properties in the mixture of signals.

On the basis of known biological data, Theis and Fuchs modeled the distribution for the case of genes that exhibit two well-defined regulatory states. Together with biologists Kevin Janes and Sameer Bajikar at the University of Virginia in Charlottesville (USA), they were able to prove experimentally that with the help of statistical methods samples containing ten cells deliver results of higher accuracy than can be achieved through analysis of the same number of single cell samples.

In many cases, several gene actions are triggered by the same factor. Even in such cases, the statistical method can be applied successfully. Fluorescent markers indicate the gene activities. The result is a mosaic, which again can be checked to spot whether different cells respond differently to the factor.

The method is so sensitive that it even shows one deviation in 40 otherwise identical cells. The fact that this difference actually is an effect and not a random outlier could be proven experimentally.

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Tracing unique cells with mathematics

Philadelphia, PA (PRWEB) January 23, 2014

Bioquark, Inc., (http://www.bioquark.com) a company focused on the development of combinatorial biologics for regeneration and disease reversion in human organs and tissues, today announces the appointment of Dr. Joel I. Osorio MD, as VP of International Clinical Development.

We are honored to have someone with Dr. Osorios experience join us as we execute on a globalized clinical strategy, said Ira S. Pastor, CEO, Bioquark Inc. His broad clinical experience in functional anti-aging regenerative and stem cell based medicine make him a very valuable addition to the Bioquark team.

Dr. Osorio brings over 9 years of experience in medical practice, both in the private practice and public medical settings. Currently the medical director of the medical spa Bamboo Rejuvenecimiento Facial y Coporal (http://www.bamboobelleza.com), Dr. Osorio has served in capacities in both private and public practice, as a hospital staff physician, and as emergency health services coordinator for a variety of private and public institutions throughout Mexico. He earned MD degrees at both Westhill University and the National Autonomous University of Mexico as a medical surgeon, has diplomas in aesthetic medicine from the Autonomous University of Guadalajara, is an Advance Fellow by the American Board of Anti-Aging and Regenerative Medicine (http://www.a4m.com/joel-osorio-bamboo-rejuvenecimiento-facial-y-corporal-naucalpan-estado-de-mxico.html), is a visiting scholar at University of North Carolina at Chapel Hill in dermatology, a fellow in stem cell medicine by the American Academy of Anti-Aging Medicine and University of South Florida, and currently is completing additional masters work in metabolic and nutrition sciences at University of South Florida. Dr. Osorio is also a member of the round table of ReGeNeRaTe Laboratories Mexico Committee (a DNAge-Lab Company), and has been actively working in the applied stem cell field since 2007. In 2011, Dr. Osorio became a member of the International Cellular Medicine Society, is a PRP certified practitioner in aesthetic and regenerative fields, and from 2009 to 2012 managed the blood bank at Ruben Lenero public hospital. Dr. Osorio frequently appears on Mexican national television programs and interviews regularly as a speaker on the topic of anti-aging (http://www.youtube.com/watch?v=Z4SvkBTS-P0) as well as contributes in various magazines and periodicals on anti-aging related subjects.

I am very excited about the candidates being developed at Bioquark and their very novel approach to human regeneration and disease reversion, as well as the broader biological programs focused on anti-aging," said Dr. Osorio. "I'm pleased to be joining the team and am looking forward to playing a more active role in this truly transformational platform."

About Bioquark, Inc. Bioquark Inc. (http://www.bioquark.com) is focused on the development of biologic based products that have the ability to alter the regulatory state of human tissues and organs, with the goal of curing a wide range of diseases, as well as effecting complex regeneration. Bioquark is developing biological pharmaceutical candidates, as well as products for the global consumer health and wellness market segments.

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Bioquark Inc. Appoints Dr. Joel I. Osorio MD, Specialist in Functional Anti-Aging Regenerative and Stem Cell Medicine ...

Jan. 16, 2014 The human body is daily exposed to external assaults such as bacteria, ultraviolet light or chemical agents. Skin, the largest organ of the body, is the first line of defense against these agents. Skin performs this function thanks to the close connections established between its cells (e.g. adherens junctions). The loss of cell adhesion between these cells is related to inflammatory diseases and cancer, hence the special interest in this area of research over the past years.

A study by the Spanish National Cancer Research Centre (CNIO), featured on the cover of the Journal of Cell Biology, shows how interactions between skin stem cells -- the cells responsible for the constant renewal of skin -- maintain the architecture of this organ. "We knew that these junctions were important in skin stem cells but the cellular components involved in their structure and function were not yet understood," says Mirna Prez-Moreno, head of the Epithelial Cellular Biology Group that led the study.

Using skin cells derived from mice, researchers have discovered that one of the key elements in the formation and stabilisation of these junctions are microtubules, tubular structures that are part of all cells and that serve as pillars to maintain their form and function.

"We have seen for the first time that skin stem-cell microtubules connect with cell-cell junctions to form velcro-like structures that hold the cells together," says Marta Shahbazi, a researcher on Prez-Moreno's team and the first author of the study.

The connection between these two cellular components -- microtubules and cell-cell junctions -- occurs via the interaction between the CLASP2 and p120 catenin proteins, linked to microtubules and cell junctions respectively.

"We found that the abscence of CLASP2 or p120 catenin in epidermal stem cells caused a loss of their adhesion, and therefore the structure of these cells," says Shahbazi.

"Our results will open up new paths for exploring how these proteins regulate skin physiology," says Prez-Moreno, adding that this knowledge will be "important for the possible development of future regenerative or anti cancer therapies."

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'Molecular scaffolding' found that maintains skin structure, organization

Stem cells have made headlines in the scientific and medical realms for over a decade, and with good reason. Some can grow into any type of cell in the body. The therapeutic potential is staggering, and researchers are working towards using stem cells to treat everything from diabetes to spinal cord injuries.

More recently, stem cell has emerged as a cosmetics industry buzzword, cropping up in product names, claims and ingredient lists. Stem cells seem ideal for anti-aging skincare, and stem cell products allude to stimulating the skin to grow new, younger cells and reverse wrinkling.

Despite products with names such as Stem Cell Therapy and StemCellin, or ingredients that include stem cell extract and stem cell conditioned media, none of the beauty creams actually contain stem cells. And, none are proven to affect your own stem cells.

MORE: The First Anti-Wrinkle Pill?

So, whats going on here? Whats in these products, if not stem cells? YouBeauty explains whats inside, why it could be dangerous and how stem cell beauty companies are skimping on science.

Meet the Stem Cells

Before we delve into the beauty creams, a brief biology lesson. Stem cells come in several varieties: embryonic (ESC), adult (ASC), induced pluripotent (iPSC) and human parthenogenetic (hpSC). All can develop into other cell types, or differentiate, but not all are created equal. And, just two relate to stem cell beauty products.

In research, ESCs come from embryos that are made from an egg fertilized outside the body, in vitro. Embryos develop from just a small cluster of cells into an entire body, thus ESCs have the potential to differentiate into nearly all cell types, from brain to heart to liver. This quality, called pluriopotency, means they could potentially be used to treat any type of diseased or injured organ or tissue.

QUIZ: How Healthy is Your Skin?

ESCs, besides being difficult to grow, face an ethical quandary: using them destroys embryos, which is why theyve ignited in political debate. In the past few years, researchers introduced two methods that attempt to mimic ESCs pluripotency sans embryo, which could eventually avoid these thorny issues. One uses a cocktail of genes to reprogram differentiated cells back into an ESC-like state (iPSC). The other uses human parthenogenetic (translation: virgin birth) embryos, which come from non-fertilized eggs, but retain some characteristics of a normal embryo (hpSC). But, ongoing research must confirm the characteristics and safety of both cell types before they can replace ESC in research. Theres a long way to go.

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Stem Cells in Skincare - YouBeauty.com

BRUSSELS - Belgian medical researchers have succeeded in repairing bones using stem cells from fatty tissue, with a new technique they believe could become a benchmark for treating a range of bone disorders.

The team at the Saint Luc university clinic hospital in Brussels have treated 11 patients, eight of them children, with fractures or bone defects that their bodies could not repair, and a spin-off is seeking investors to commercialise the discovery.

Doctors have for years harvested stem cells from bone marrow at the top of the pelvis and injected them back into the body to repair bone.

The ground-breaking technique of Saint Luc's centre for tissue and cellular therapy is to remove a sugar cube sized piece of fatty tissue from the patient, a less invasive process than pushing a needle into the pelvis and with a stem cell concentration they say is some 500 times higher.

The stem cells are then isolated and used to grow bone in the laboratory. Unlike some technologies, they are also not attached to a solid and separate 'scaffold'.

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Stem cells from fatty tissue show potential for bone repair

Indian J Orthop. 2012 Jan-Feb; 46(1): 1018.

Department of University Health Network, Toronto Western Hospital, Toronto, Canada, ON M5T 2S8

Address for correspondence: Dr. Michael Fehlings, University Health Network, Toronto Western Research Institute, Main Pavilion, 12th Floor, 399 Bathurst Street, Toronto, Canada ON M5T 2S8. E-mail: michael.fehlings/at/uhn.ca

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Spinal cord injury (SCI) is a devastating condition associated with significant functional and sensory deficits, emotional, social, and financial burdens, and an increased risk of cardiovascular complications, deep vein thrombosis, osteoporosis, pressure ulcers, autonomic dysreflexia, and neuropathic pain.

The estimated annual global incidence of SCI is 1540 cases per million. In the USA, approximately 1.275 million individuals are affected, with over 12,000 new cases each year.15 The most common causes of traumatic SCI are road traffic accidents, falls, occupational and sports-related injuries that result in contusion and compression of the spinal cord.1 Approximately 55% of SCIs occur at the cervical level (C1 to C7-T1) with a mortality of 10% in the first year following injury and an expected lifespan of only 1015 years post-injury, and thoracic (T1T11), thoracolumbar (T11T12 to L1L2) and lumbosacral (L2S5) injuries each account for approximately 15% of SCI.14 Depending on the age of the patient, severity, and levels of SCI, the lifetime cost of health care and other injury-related expenses can reach $25 million.15

Despite advances in pre-hospital care, medical and surgical management and rehabilitation approaches, many SCI sufferers still experience substantial neurological disability. Intensive efforts are underway to develop effective neuroprotective and regenerative strategies.

SCI involves a primary (the physical injury) and a secondary injury (the subsequent cascade of molecular and cellular events which amplify the original injury).6 The primary injury damages both upper and lower motor neurons and disrupts motor, sensory and autonomic functions. Pathophysiological processes occurring in the secondary injury phase are rapidly instigated in response to the primary injury in an attempt to homeostatically control and minimize the damage. Paradoxically, this response is largely responsible for exacerbating the initial damage and creating an inhibitory milieu that prevents endogenous efforts of repair, regeneration and remyelination. These secondary processes include inflammation, ischemia, lipid peroxidation, production of free radicals, disruption of ion channels, axonal demyelination, glial scarring (astrogliosis), necrosis and programmed cell death. Nevertheless, endogenous repair and regenerative mechanisms during the secondary phase of injury minimize the extent of the lesion (through astrogliosis), reorganize blood supply through angiogenesis, clear cellular debris, and reunite and remodel damaged neural circuits. The spatial and temporal dynamics of these secondary mediators7 are fundamental to SCI pathophysiology and as such offer exploitable targets for therapeutic intervention.

A multitude of characteristics of cells tested pre-clinically and clinically make them attractive to potentially address the multifactorial nature of the pathophysiology of secondary SCI they are anti-inflammatory, immunomodulatory,812 anti-gliotic,13 pro-oligodendrogliogenic,14 pro-neuronogenic,15 and secrete various anti-apoptotic and pro-angiogenic neurotrophic factors. Given the pathophysiological targets of SCI,7 transplanted cells should: 1) enable regenerating axons to cross barriers; 2) functionally replace lost cells; and/or 3) create an environment supportive of neural repair.16 However, given the multifactorial nature of SCI and its dynamic pathophysiological consequences, the success of future clinical trials of cell therapy will likely depend on the informed co-administration of multiple strategies, including pharmacological and rehabilitation therapies.7

Different sources and types of cells have been and/or are being tested in clinical trials for SCI, including embryonic stem cells (ESCs), neural progenitor cells (NPCs), bone marrow mesenchymal cells (BMSCs) and non-stem cells such as olfactory ensheathing cells and Schwann cells.17 Other cell types are being developed for the clinic, including other sources of mesenchymal cells (fetal blood,18 adipose tissue, umbilical cord1936), adult21,37 and immortalized neural progenitors (PISCES, NCT01151124), skin-derived progenitors,3847 induced pluripotent stem cells4852 and endogenous spinal cord progenitors5358 []. The advantages and disadvantages of each cell source and type being considered or already in clinical trials for SCI have been extensively described and compared elsewhere,17,5963 and reflect their potential in the clinic []. There are currently more than a dozen cell therapy clinical trials for SCI listed on clinicaltrials.gov.64 Most are Phase I or I/II clinical safety and feasibility studies, indicating that cellular treatments for SCI developed in the laboratory are still in the very early stages of clinical translation.

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Current stem cell treatments for spinal cord injury

Jan. 13, 2014 Geneticists from Ohio, California and Japan joined forces in a quest to correct a faulty chromosome through cellular reprogramming. Their study, published online today in Nature, used stem cells to correct a defective "ring chromosome" with a normal chromosome. Such therapy has the promise to correct chromosome abnormalities that give rise to birth defects, mental disabilities and growth limitations.

"In the future, it may be possible to use this approach to take cells from a patient that has a defective chromosome with multiple missing or duplicated genes and rescue those cells by removing the defective chromosome and replacing it with a normal chromosome," said senior author Anthony Wynshaw-Boris, MD, PhD, James H. Jewell MD '34 Professor of Genetics and chair of Case Western Reserve School of Medicine Department of Genetics and Genome Sciences and University Hospitals Case Medical Center.

Wynshaw-Boris led this research while a professor in pediatrics, the Institute for Human Genetics and the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UC, San Francisco (UCSF) before joining the faculty at Case Western Reserve in June 2013.

Individuals with ring chromosomes may display a variety of birth defects, but nearly all persons with ring chromosomes at least display short stature due to problems with cell division. A normal chromosome is linear, with its ends protected, but with ring chromosomes, the two ends of the chromosome fuse together, forming a circle. This fusion can be associated with large terminal deletions, a process where portions of the chromosome or DNA sequences are missing. These deletions can result in disabling genetic disorders if the genes in the deletion are necessary for normal cellular functions.

The prospect for effective counter measures has evaded scientists -- until now. The international research team discovered the potential for substituting the malfunctioning ring chromosome with an appropriately functioning one during reprogramming of patient cells into induced pluripotent stem cells (iPSCs). iPSC reprogramming is a technique that was developed by Shinya Yamanaka, MD, PhD, a co-corresponding author on the Nature paper. Yamanaka is a senior investigator at the UCSF-affiliated Gladstone Institutes, a professor of anatomy at UCSF, and the director of the Center for iPS Cell Research and Application (CiRA) at the Institute for Integrated Cell-Material Sciences (iCeMS) in Kyoto University. He won the Nobel Prize in Medicine in 2012 for developing the reprogramming technique.

Marina Bershteyn, PhD, a postdoctoral fellow in the Wynshaw-Boris lab at UCSF, along with Yohei Hayashi, PhD, a postdoctoral fellow in the Yamanaka lab at the Gladstone Institutes, reprogrammed skin cells from three patients with abnormal brain development due to a rare disorder called Miller Dieker Syndrome, which results from large terminal deletions in one arm of chromosome 17. One patient had a ring chromosome 17 with the deletion and the other two patients had large terminal deletions in one of their chromosome 17, but not a ring. Additionally, each of these patients had one normal chromosome 17.

The researchers observed that, after reprogramming, the ring chromosome 17 that had the deletion vanished entirely and was replaced by a duplicated copy of the normal chromosome 17. However, the terminal deletions in the other two patients remained after reprogramming. To make sure this phenomenon was not unique to ring chromosome 17, they reprogrammed cells from two different patients that each had ring chromosomes 13. These reprogrammed cells also lost the ring chromosome, and contained a duplicated copy of the normal chromosome 13.

"It appears that ring chromosomes are lost during rapid and continuous cell divisions during reprogramming," said Yamanaka. "The duplication of the normal chromosome then corrects for that lost chromosome."

"Ring loss and duplication of whole chromosomes occur with a certain frequency in stem cells," explained Bershteyn. "When chromosome duplication compensates for the loss of the corresponding ring chromosome with a deletion, this provides a possible avenue to correct large-scale problems in a chromosome that have no chance of being corrected by any other means."

"It is likely that our findings apply to other ring chromosomes, since the loss of the ring chromosome occurred in cells reprogrammed from three different patients," said Hayashi.

Originally posted here:
Study discovers chromosome therapy to correct severe chromosome defect

Ryan White, CTV Calgary Published Friday, January 10, 2014 3:37PM MST Last Updated Friday, January 10, 2014 7:10PM MST

Alex Petric is hoping his part in an international clinical trial at the Foothills Hospital will assist researchers in the development of a treatment for spinal cord injuries.

Alex, a paramedic from Winnipeg, was paralyzed during a winter holiday in Panama with his girlfriend. The 28-year-old dove headfirst into what he believed to be deep water.

Immediately I felt paralyzed, right when I came up, recollects Alex. You just know youre in a lot of trouble. Youre trying your hardest to move your legs and its not happening.

Ten months after the accident, 29-year-old Alex is taking part in a medical trial to determine the safety of stem cell therapy on patients with spinal cord injuries.

While the trial, conducted by researchers from the University of Calgary, focuses on safety, the ultimate goal is to develop a cure for spinal cord injuries which could require multiple therapies.

The medical team, led by Dr. Steve Casha, will make a small incision in order to view Alexs injury. Once the precise location of the injury has been determined, then stem cells are injected above and below to potentially recreate the lost tissue.

The approach is regeneration, explains Dr. Casha, to reverse the damage that has been done.

Researchers and Alex are realistic in their expectations of the treatment despite the fact two previous patients in the study have regained sensation.

I just feel like I am part of something that could give people hope, including myself, said Alex. We don't know what will happen with this surgery. They're trying to fix us, basically trying to make us normal again.

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Calgary medical team attempting stem cell therapy on paralyzed man

Blood stem cells can only thrive in the bone marrow, from which they turn into different kinds of blood cells that are needed in the body, including red and white blood cells, which transport oxygen and fight disease. For years, researchers around the world have been trying to find a way to replicate the bone marrow so that they are able to harvest blood stem cells in the laboratory because stem cells cease to be what they are once they are removed from the body.

Now researchers at Karlsruhe Institute of Technology, the Max Planck Institute for Intelligent Systems and the University of Tbingen say that they have designed porous material in which blood stem cells can multiply for as long as four days.

A bath sponge with cells inside

Natural bone marrow is a very complex structure, making it difficult to imitate. Its three-dimensional porous architecture resembles a bath sponge and contains bridging proteins that the stem cells can dock on.

Precisely-sized pores host many cell types that interact with each other and produce chemical messages, allowing the blood stem cells to multiply.

Researchers put a porous polymer into a nutrient solution to cultivate stem cells inside

"We assume that stem cells [do] not only notice the chemical composition of their surroundings. They can probably also feel if their environment is soft or hard, rough or smooth," Cornelia Lee-Thedieck, a researcher at the Karlsruhe Institute of Technology tells DW.

She and her colleagues put everything together that researchers already know about bone marrow and their preferred environment. They replicated the sponge-like structure of bone marrow using a simple polymer. They linked proteins to it and added other cell types.

Treating leukemia

The researchers would like to see the artificial bone marrow help cure leukemia one day. Since new, healthy blood stem cells are needed to treat leukemia, stem cells could be harvested in the lab and transplanted into patients. Currently, the stem cells are isolated from the blood or the bone marrow of a suitable donor.

The rest is here:
Scientists create artificial bone marrow that helps stem cells thrive

24OrasGMA January 10, 2014, 7:34 pm Friday Bawal na bawal ang magsakay sa motorsiklo ng batang 8 taong gulang pababa, may helmet

24OrasGMA January 10, 2014, 7:30 pm Friday Sen. Jinggoy Estrada, nagsumite na rin ng counter-affidavit kaugnay ng pork barrel scam. #BantayKaban

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24OrasGMA January 10, 2014, 7:23 pm Friday Ngayon nga, may halos 3,000 container ng mga bigas sa Manila Port, na hinihinalang ipinuslit

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24OrasGMA January 10, 2014, 7:21 pm Friday #ChikaMinute: Laking pasalamat ni Geoff Eigenmann dahil sa mga bago niyang projects kasunod ng pagbabawas

24OrasGMA January 10, 2014, 7:20 pm Friday Mga prepaid card ang gagamitin sa pagbabayad ng pasahe sa COMET.

24OrasGMA January 10, 2014, 7:20 pm Friday Mainam daw ito sa kalikasan dahil 'di nagbubuga ng maitim na usok.

24OrasGMA January 10, 2014, 7:19 pm Friday City Optimized Managed Environmental Transport o COMET, mas pina-high tech daw na e-jeepney. Nakatutok si

24OrasGMA January 10, 2014, 7:18 pm Friday Nasa okasyon din sina Sarangani Representative @MannyPacquiao at BIR Commissioner Kim Henares na nakita pang

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Bone marrow stem cells could defeat drug-resistant TB, trial study finds

Abstract

The skin constantly renews itself throughout adult life, and the hair follicle undergoes a perpetual cycle of growth and degeneration. Stem cells (SCs) residing in the epidermis and hair follicle ensure the maintenance of adult skin homeostasis and hair regeneration, but they also participate in the repair of the epidermis after injuries. We summarize here the current knowledge of epidermal SCs of the adult skin. We discuss their fundamental characteristics, the methods recently designed to isolate these cells, the genes preferentially expressed in the multipotent SC niche, and the signaling pathways involved in SC niche formation, SC maintenance, and activation. Finally, we speculate on how the deregulation of these pathways may lead to cancer formation.

Keywords: hair follicle, multipotency, self-renewal, cell fate determination, Wnt signaling, Bmp, cancer

Skin and its appendages ensure a number of critical functions necessary for animal survival. Skin protects animals from water loss, temperature change, radiation, trauma, and infections, and it allows animals to perceive their environment through tactile sense. Through camouflage, the skin provides protection against predators, and it also serves as decoration for social and reproductive behavior.

Adult skin is composed of a diverse organized array of cells emanating from different embryonic origins. In mammals, shortly after gastrulation, the neurectoderm cells that remain at the embryo surface become the epidermis, which begins as a single layer of unspecified progenitor cells. During development, this layer of cells forms a stratified epidermis (sometimes called interfollicular epidermis), the hair follicles (HRs), sebaceous glands, and, in nonhaired skin, the apocrine (sweat) glands. Mesoderm-derived cells contribute to the collagen-secreting fibroblasts of the underlying dermis, the dermovasculature that supplies nutrients to skin, arrector pili muscles that attach to each hair follicle (HF), the subcutaneous fat cells, and the immune cells that infiltrate and reside in the skin. Neural crestderived cells contribute to melanocytes, sensory nerve endings of the skin, and the dermis of the head. Overall, approximately 20 different cell types reside within the skin.

In the adult, many different types of stem cells (SCs) function to replenish these various cell types in skin as it undergoes normal homeostasis or wound repair. Some SCs (e.g., those that replenish lymphocytes) reside elsewhere in the body. Others (e.g., melanoblasts and epidermal SCs) reside within the skin itself. This review concentrates primarily on epidermal SCs, which possess two essential features common to all SCs: They are able to self-renew for extended periods of time, and they differentiate into multiple lineages derived from their tissue origin (Weissman et al. 2001).

Mature epidermis is a stratified squamous epithelium whose outermost layer is the skin surface. Only the innermost (basal) layer is mitotically active. The basal layer produces, secretes, and assembles an extracellular matrix (ECM), which constitutes much of the underlying basement membrane that separates the epidermis from the dermis. The most prominent basal ECM is laminin5, which utilizes 31-integrin for its assembly. As cells leave the basal layer and move outward toward the skin surface, they withdraw from the cell cycle, switch off integrin and laminin expression, and execute a terminal differentiation program. In the early stages of producing spinous and granular layers, the program remains transcriptionally active. However, it culminates in the production of dead flattened cells of the cornified layer (squames) that are sloughed from the skin surface, continually being replaced by inner cells moving outward ().

Epidermal development and hair follicle morphogenesis. The surface of the early embryo is covered by a single layer of ectodermal cells that adheres to an underlying basement membrane of extracellular matrix. As development proceeds, the epidermis progressively ...

The major structural proteins of the epidermis are keratins, which assemble as obligate heterodimers into a network of 10-nm keratin intermediate filaments (IFs) that connect to 64-integrin-containing hemidesmosomes that anchor the base of the epidermis to the laminin5-rich, assembled ECM. Keratin IFs also connect to intercellular junctions called desmosomes, composed of a core of desmosomal cadherins. Together, these connections to keratin IFs provide an extensive mechanical framework to the epithelium (reviewed in Omary et al. 2004). The basal layer is typified by the expression of keratins K5 and K14 (also K15 in the embryo), whereas the intermediate suprabasal (spinous) layers express K1 and K10. Desmosomes connected to K1/K10 IFs are especially abundant in suprabasal cells, whereas basal cells possess a less robust network of desmosomes and K5/K14. Rather, basal cells utilize a more dynamic cytoskeletal network of microtubules and actin filaments that interface through -and -catenins to E-cadherin-mediated cell-cell (adherens) junctions, in addition to the 1-integrin-mediated cell-ECM junctions (reviewed in Green et al. 2005, Perez-Moreno et al. 2003). Filaggrin and loricrin are produced in the granular layer. The cornified envelope seals the epidermal squames and provides the barrier that keeps microbes out and essential fluids in (Candi et al. 2005, Fuchs 1995) (). The program of terminal differentiation in the epidermis is governed by a number of transcription factor families, including AP2, AP1, C/EBPs, Klfs, PPARs, and Notch (reviewed in Dai & Segre 2004).

Although the molecular mechanisms underlying the process of epidermal stratification are still unfolding, several studies have recently provided clues as to how this might happen. Increasing evidence suggests the transcription factor p63 might be involved. Mice null for the gene encoding p63 present an early block in the program of epidermal stratification (Mills et al. 1999, Yang et al. 1999).

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Epidermal Stem Cells of the Skin

PUBLIC RELEASE DATE:

9-Jan-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (Jan. 9, 2014) Using skin-derived stem cells (SDSCs) and a previously developed collagen tube designed to successfully bridge gaps in injured nerves in rat models, the research team in Milan, Italy that established and tested the procedure has successfully rescued peripheral nerves in the upper arms of a patient suffering peripheral nerve damage who would have otherwise had to undergo amputations.

The study will be published in a future issue of Cell Transplantation but is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-ct1096.

"Peripheral nerve repair with satisfactory functional recovery remains a great surgical challenge, especially for severe nerve injuries resulting in extended nerve defects," said study corresponding author Dr. Yvan Torrente, of the Department of Pathophysiology and Transplantation at the University of Milan. "However, we hypothesized that the combination of autologous (self-donated) SDSCs placed in collagen tubes to bridge gaps in the damaged nerves would restore the continuity of injured nerves and save from amputation the upper arms of a patient with poly-injury to motor and sensory nerves."

Although autologous nerve grafting has been the 'gold standard' for reconstructive surgeries, these researchers felt that there were several drawbacks to that approach, including graft availability, donor site morbidity, and neuropathic pain.

According to the researchers, autologous SDSCs have advantages over other stem cells as they are an accessible source of stem cells rapidly expandable in culture, and capable of survival and integration within host tissues.

While the technique of using the collagen tubes - NeuraGen, an FDA-approved device - to guide the transplanted cells over gaps in the injured nerve had been previously developed and tested by the same researchers with the original research successfully saving damaged sciatic nerves on rats, the present case, utilizing the procedure they developed employing SDSCs and a nerve guide, is the first to be carried out on a human.

Over three years, the researchers followed up on the patient, assessing functional recovery of injured median and ulnar nerves by pinch gauge test and static two-point discrimination and touch test with monofiliments along with electrophysiological and MRI examinations.

Originally posted here:
Stem cells injected into nerve guide tubes repair injured peripheral nerve

PUBLIC RELEASE DATE:

8-Jan-2014

Contact: David McKeon DMckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation

NEW YORK, NY (January 8, 2014) Scientists at The New York Stem Cell Foundation (NYSCF) Research Institute in collaboration with scientists at the Icahn School of Medicine at Mount Sinai (ISMMS) successfully generated a stem cell model of familial Alzheimer's disease (FAD). Using this stem cell model, researchers identified fourteen genes that may be implicated in the disease and one gene in particular that shows the importance that inflammation may play in the brain of Alzheimer's patients.

In this study, published today in PLOS ONE, the team of scientists produced stem cells and neural precursor cells (NPCs), representing early neural progenitor cells that build the brain, from patients with severe early-onset AD with mutations in the Presenilin 1 (PSEN1) gene. These NPCs had elevated Abeta42/Abeta40 ratios, indicating elevation of the form of amyloid found in the brains of Alzheimer's patients. These levels were greater than those in adult cells that did not have the PSEN1mutation. This elevated ratio showed that these NPCs grown in the petri dish were accurately reflecting the cells in the brains of FAD patients.

"Our ability to accurately recapitulate the disease in the petri dish is an important advance for this disease. These genes provide us with new targets to help elucidate the cause of sporadic forms of the disease as well provide targets for the discovery of new drugs," said Susan L. Solomon, Chief Executive Officer of The New York Stem Cell Foundation.

"The gene expression profile from Noggle's familial Alzheimer's stem cells points to inflammation which is especially exciting because we would not usually associate inflammation with this particular Alzheimer's gene. The greatest breakthroughs come with 'unknown unknowns', that is, things that we don't know now and that we would never discover through standard logic," said Sam Gandy, MD, PhD, Professor of Neurology and Psychiatry and Director of the Center for Cognitive Health at the Icahn School of Medicine at Mount Sinai and a co-author on the study. Gandy is also Associate Director of the NIH-Designated Mount Sinai Alzheimer's Disease Research Center.

The researchers generated induced pluripotent stem (iPS) cells from affected and unaffected individuals from two families carrying PSEN1 mutations. After thorough characterization of the NPCs through gene expression profiling and other methods, they identified fourteen genes that behaved differently in PSEN1 NPCs relative to NPCs from individuals without the mutation. Five of these targets also showed differential expression in late onset Alzheimer's disease patients' brains. Therefore, in the PSEN1 iPS cell model, the researchers reconstituted an essential feature in the molecular development of familial Alzheimer's disease.

Although the majority of Alzheimer's disease cases are late onset and likely result from a mixture of genetic predisposition and environmental factors, there are genetic forms of the disease that affect patients at much earlier ages. PSEN1 mutations cause the most common form of inherited familial Alzheimer's disease and are one hundred percent penetrant, resulting in all individuals with this mutation getting the disease.

The identification of genes that behaved differently in patients with the mutation provides new targets to further study and better understand their effects on the development of Alzheimer's disease. One of these genes, NLRP2, is traditionally thought of as an inflammatory gene.

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Stem cell research identifies new gene targets in patients with Alzheimer's disease

Despite some ethical concerns, most patients are now broadly endorsing stem cell research.

In the case of induced pluripotent stem cells (iPSCs), which are stem cells made from skin or other tissues, researchers at the Johns Hopkins University found patients were largely in favour of participating in iPSC research even if personal benefit was unlikely.

The patients, however, raised concerns about consent, privacy and transparency.

"Bioethicists as well as stem cell researchers and policy-makers have discussed ethical issues at length but till date, we didn't have any systematic information about what patients think about these issues," said Jeremy Sugarman, the Harvey M. Meyerhoff professor of bioethics and medicine at Johns Hopkins Berman Institute of Bioethics.

Unlike human embryonic stem cells, iPSCs are derived without destroying a human embryo. Research with human iPSCs is valuable for developing new drugs, studying disease, and perhaps developing medical treatments, said the study published in the journal Cell Stem Cell.

According to the study, consent was highly important for patients. Some patients even suggested that proper informed consent could compensate for other concerns they had about privacy, the "immortalisation" of cells and the commercialisation of stem cells.

There was a "strong desire among participants to have full disclosure of the anticipated uses, with some participants wanting to be able to veto certain uses of their cells", the study added.

"The idea that donated cells would potentially live forever was unnerving to some participants," the report stated.

"This study is a first step in getting crucial information about what values are factored into a decision to participate in iPSC research, and what those participants expect from the experience," said Sugarman.

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Patients endorse key stem cell research