Patch created to repair damaged heart tissue
Wednesday, 14 October 2009
By mimicking the way embryonic stem cells develop into heart muscle in a lab, Duke University bioengineers believe they have taken an important first step toward growing a living "heart patch" to repair heart tissue damaged by disease.
In a series of experiments using mouse embryonic stem cells, the bioengineers used a novel mould of their own design to fashion a three-dimensional "patch" made up of heart muscle cells, known as cardiomyocytes. The new tissue exhibited the two most important attributes of heart muscle cells – the ability to contract and to conduct electrical impulses. The mould looks much like a piece of Chex cereal in which researchers varied the shape and length of the pores to control the direction and orientation of the growing cells.
The researchers grew the cells in an environment much like that found in natural tissues. They encapsulated the cells within a gel composed of the blood-clotting protein fibrin, which provided mechanical support to the cells, allowing them to form a three-dimensional structure. They also found that the cardiomyocytes flourished only in the presence of a class of "helper" cells known as cardiac fibroblasts, which comprise as much as 60 percent of all cells present in a human heart.
"If you tried to grow cardiomyocytes alone, they develop into an unorganized ball of cells," said Brian Liau, graduate student in biomedical engineering at Duke's Pratt School of Engineering. Liau, who works in the laboratory of assistant professor Nenad Bursac, presented the results of his latest experiments during the annual scientific sessions of the Biomedical Engineering Society in Pittsburgh.
"We found that adding cardiac fibroblasts to the growing cardiomyocytes created a nourishing environment that stimulated the cells to grow as if they were in a developing heart," Liau said.
"When we tested the patch, we found that because the cells aligned themselves in the same direction, they were able to contract like native cells. They were also able to carry the electrical signals that make cardiomyocytes function in a coordinated fashion."
"The addition of fibroblasts in our experiments provided signals that we believe are present in a developing embryo," Liau said. The need for helper cells is not uncommon in mammalian development. For example, he explained, nerve cells need "sheathe" cells known as glia in order to develop and function properly.
Bursac believes that the latest experiments represent a proof-of-principle advance, but said there are still many hurdles to overcome before such patches could be implanted into humans with heart disease.
"While we were able to grow heart muscle cells that were able to contract with strength and carry electric impulses quickly, there are many other factors that need to be considered," Bursac said.
"The use of fibrin as a structural material allowed us to grow thicker, three-dimensional patches, which would be essential for the delivery of therapeutic doses of cells. One of the major challenges then would be establishing a blood vessel supply to sustain the patch."
The researchers plan to test their model using non-embryonic stem cells. For use in humans, this is important for many reasons, both scientifically and ethically, Bursac said. Recent studies have demonstrated that some cells from human adults have the ability to be reprogrammed to become similar to embryonic stem cells.
"Human cardiomyocytes tend to grow a lot slower than those of mice," Bursac said.
"Since it takes nine months for the human heart to complete development, we need to find a way to get the cells to grow faster while maintaining the same essential properties of native cells."
If they could use a patient's own cells, the patch would also evade an immune system reaction, Bursac added.
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Wednesday, 14 October 2009
New Strategy for Mending Broken Hearts?
Liver Cells Grown from Patients' Skin Cells
Treatment of liver diseases possible
Wednesday, 14 October 2009
Scientists at The Medical College of Wisconsin in Milwaukee have successfully produced liver cells from patients' skin cells opening the possibility of treating a wide range of diseases that affect liver function. The study was led by Stephen A. Duncan, D. Phil., Marcus Professor in Human and Molecular Genetics, and professor of cell biology, neurobiology and anatomy, along with postdoctoral fellow Karim Si-Tayeb, Ph.D., and graduate student Ms. Fallon Noto.
"This is a crucial step forward towards developing therapies that can potentially replace the need for scarce liver transplants, currently the only treatment for most advanced liver disease," says Dr. Duncan.
Liver disease is the fourth leading cause of death among middle aged adults in the United States. Loss of liver function can be caused by several factors, including genetic mutations, infections with hepatitis viruses, by excessive alcohol consumption, or chronic use of some prescription drugs. When liver function goes awry it can result in a wide variety of disorders including diabetes and atherosclerosis and in many cases is fatal.
The Medical College research team generated patient–specific liver cells by first repeating the work of James Thomson and colleagues at University of Wisconsin-Madison who showed that skin cells can be reprogrammed to become cells that resemble embryonic stem cells. They then tricked the skin–derived pluripotent stem cells into forming liver cells by mimicking the normal processes through which liver cells are made during embryonic development. Pluripotent stem cells are so named because of their capacity to develop into any one of eh more than 200 cell types in the human body.
At the end of this process, the researchers found that they were able to very easily produce large numbers of relatively pure liver cells in laboratory culture dishes.
"We were excited to discover that the liver cells produced from human skin cells were able to perform many of the activities associated with healthy adult liver function and that the cells could be injected into mouse livers where they integrated and were capable of making human liver proteins," says Dr. Duncan.
Several studies have shown that liver cells generated from embryonic stem cells could potentially be used for therapy. However, the possible use of such cells is limited by ethical considerations associated with the generation of embryonic stem cells from preimplantation embryos and the fact that embryonic stem cells do not have the same genetic make-up as the patient.
Although the investigations are still at an early stage the researchers believe that the reprogrammed skin cells could be used to investigate and potentially treat metabolic liver disease. The liver may be particularly suitable for stem-cell based therapies because it has a remarkable capacity to regenerate. It is interesting to note that the regenerative nature of the liver was referenced in the ancient Greek tale of Prometheus. When Prometheus was caught stealing the gift of fire from Zeus, he was punished by having his liver eaten daily by an eagle. This provided the eagle with an everlasting meal because each night the liver of Prometheus would re-grow.
The liver is a central regulator of the body's metabolism and is responsible for controlling sugar and cholesterol levels, secretion of a variety of hormones, production of blood clotting factors, and has an essential role in preventing toxins from damaging other organs in the body.
It is possible that in the future a small piece of skin from a patient with loss of liver function could be used to produce healthy liver cells, replacing the diseased liver with normal tissue.
Recently, the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases through the American Recovery and Reinvestment Act have provided the MCW researchers, in collaboration with Markus Grompe, M.D., at the Oregon Health and Science University, a $1 million research grant to pursue the possibility of using reprogrammed skin cells to study and treat metabolic liver disease. Using this support, as well as donations from individuals throughout Milwaukee, the Medial College researchers are currently producing reprogrammed cells from patients suffering from diabetes, hyperlipidemia, and hypercholesterolemia in an effort to identify new treatments for these diseases.
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ZenMaster
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Monday, 12 October 2009
Jumping Genes, Gene Loss and Genome Dark Matter
New map of copy number variation in the human genome is a resource for human genetics
Monday, 12 October 2009
In research published last week by Nature, an international team describes the finest map of changes to the structure of human genomes and a resource they have developed for researchers worldwide to look at the role of these changes in human disease. They also identify 75 'jumping genes' - regions of our genome that can be found in more than one location in some individuals.
However, the team cautions that they have not found large numbers of candidates that might alter susceptibility to complex diseases such as diabetes or heart disease among the common structural variants. They suggest strategies for finding this 'dark matter' of genetic variation.
Human genomes differ because of single-letter variations in the genetic code and also because whole segments of the code might be deleted or multiplied in different human genomes. These larger, structural differences are called copy number variants (CNVs).
The new research to map and characterize CNVs is of a scale and a power unmatched to date, involving hundreds of human genomes, billions of data points and many thousands of CNVs.
"This study is more than ten times as powerful as our first map, published three years ago," explains Dr Matt Hurles from the Wellcome Trust Sanger Institute and a leader on the project, "and much more detailed than any other. Importantly, we have also assigned the CNVs to a specific genetic background so that they can be readily examined in disease studies carried out by others, such as the Wellcome Trust Case Control Consortium.”
"Nevertheless, we have not found large numbers of common CNVs that we can tie strongly to disease. There remains much to be discovered and much to understand and our freely available genotyped collection will drive that discovery."
The results show that any two genomes differ by more than 1000 CNVs, or around 0.8% of a person's genome sequence. Most of these CNVs are deletions, with a minority being duplications.
Two consequences are particularly striking in this study of apparently healthy people. First, 75 regions have jumped around in the genomes of these samples; second, more than 250 genes can lose one of the two copies in our genome without obvious consequences and a further 56 genes can fuse together potentially to form new composite genes.
"This paper detailing common CNVs in different world populations, and providing the first glimpse into evolutionary biology of such class of human variation, is unquestionably one of the most important advances in human genome research since the completion of a reference human genome," says Professor James R. Lupski, Vice Chair of the department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
"It complements the cataloguing of single nucleotide variation delineated in the HapMap Project and will both enable some new approaches to, and further augment other studies of, basic human biology relevant to health and disease."
"The genetic 'blueprint' of humans is the human genome," says Sir Mark Walport, Director of the Wellcome Trust.
"But we are each unique as individuals, shaped by variation in both genome and environment. Understanding the variation amongst human genomes is key to understanding the inherited differences between each of us in health and disease. A whole new dimension has been added to our understanding of variation in the human genome by the identification of copy number variants."
The results also give, for the first time, a minimum measure of the rate of CNV mutation: at least one in 17 children will have a new CNV. In many cases, that CNV will have no obvious clinical consequences. However, for some the effects are severe. In those cases the data are captured in the DECIPHER database, a repository of clinical information about CNVs designed to aid the diagnosis of rare disorders in young children.
However, CNVs are not only about here and about now; they are also ancient legacies of how our ancestors adapted to their environments. Among the most impressive variations between populations are CNVs that modify the activity of the immune system, known to be evolving rapidly in human populations, and genes implicated in muscle function. The researchers propose that the consequences of these CNVs can be dissected in population studies.
The team scanned 42 million locations on the genomes of 40 people, half of European ancestry and half of West-African ancestry. The scale of the method meant they could detect CNVs as small as 450 bases occurring in one in 20 individuals.
However, the researchers concede that their map of common variants will not account for much of the 'dark matter' of the genome - the missing heritability where, despite diligent searches, genetic variants have not been found for common disease.
"CNV studies have made huge advances in the past few years, but we are still looking only at the most common CNVs," explains Dr Steve Scherer of the Hospital for Sick Children, Toronto.
"We suspect that there are many CNVs that have real clinical consequences that occur in perhaps one in 50 or one in 100 people - below the level we have detected.”
"Success in the hunt for the missing genetic causes of common disease has become possible in the last few years and we expect to find more as higher resolution searches become possible."
The research group have maximized the value of their research by not only mapping the CNVs, but by also genotyping them - assigning them to a specific genetic background that makes them readily useful in wider genetic studies, such as the Wellcome Trust Case Control Consortium.
"We were determined to develop not only the map, but also to provide the resources that help other researchers and clinical cytogeneticists most rapidly use our CNV results," comments Dr Charles Lee, one of the project leaders from Brigham and Women's Hospital and Harvard Medical School in Boston, USA.
"Already, the data that we have generated is benefiting other large-scale studies such as the 1000 Genomes Projects as well as making an enormous difference in the accurate interpretation of clinical genetic diagnoses.”
"Nonetheless, the human CNV story is far from over."
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Chromosomes are shown colour-coded in the outermost circle. Inside are lines connecting the origin and the new location (where known) of 58 out of 75 putative inter-chromosomal duplications, coloured according to their chromosome of origin. Credit: Jan Aerts, Wellcome Trust Sanger Institute.
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Major Improvements Made in Engineering Heart Repair Patches from Stem Cells
Pre-formed blood vessels in patches connect to rodents' heart circulation
Monday, 12 October 2009
University of Washington (UW) researchers have succeeded in engineering human tissue patches free of some problems that have stymied stem-cell repair for damaged hearts.
The disk-shaped patches can be fabricated in sizes ranging from less than a millimetre to a half-inch in diameter. Until now, engineering tissue for heart repair has been hampered by cells dying at the transplant core, because nutrients and oxygen reached the edges of the patch but not the centre. To make matters worse, the scaffolding materials to position the cells often proved to be harmful.
Heart tissue patches composed only of heart muscle cells could not grow big enough or survive long enough to take hold after they were implanted in rodents, the researchers noted in their article, published last month in the Proceedings of the National Academy of Sciences. The researchers decided to look at the possibility of building new tissue with supply lines for the oxygen and nutrients that living cells require.
The scientists testing this idea are from the UW Center for Cardiovascular Biology and the UW Institute for Stem Cell and Regenerative Medicine, under the guidance of senior author Dr. Charles "Chuck" Murry, professor of pathology and bioengineering. The lead author is Dr. Kelly R. Stevens, a UW doctoral student in bioengineering who came up with solutions to the problems observed in previous grafts. The study is part of a collaborative tissue engineering effort called BEAT (Biological Engineering of Allogeneic Tissue).
Stevens and her fellow researchers added two other types of cells to the heart muscle cell mixture. These were cells similar to those that line the inside of blood vessels and cells that provide the vessel's muscular support. All of the heart muscle cells were derived from embryonic stem cells, while the vascular cells were derived from embryonic stem cells or a variety of more mature sources such as the umbilical cord. The resulting cell mixture began forming a tissue containing tiny blood vessels.
"These were rudimentary blood vessel networks like those seen early in embryonic development," Murry said.
In contrast to the heart muscle cell-only tissue, which failed to survive transplantation and which remained apart from the rat's heart circulatory system, the pre-formed vessels in the mixed-cell tissue joined with the rat's heart circulatory system and delivered rat blood to the transplanted graft.
"The viability of the transplanted graft was remarkably improved," Murry observed.
"We think the gain in viability is due to the ability for the tissue to form blood vessels."
Equally as exciting, the scientists observed that the patches of engineered tissue actively contracted. Moreover, these contractions could be electronically paced, up to what would translate to 120 beats per minute. Beyond that point, the tissue patch did not relax fully and the contractions weakened. However, the average resting adult heart pulses about 70 beats per minute. This suggests that the engineered tissue could, within limits, theoretically keep pace with typical adult heart muscle, according to the study authors.
Another physical quality that made the mixed-cell tissue patches superior to heart muscle-cell patches was their mechanical stiffness, which more closely resembled human heart muscle. This was probably due to the addition of supporting cells, which created connective tissues. Passive stiffness allows the heart to fill properly with blood before it contracts.
When the researchers implanted these mixed celled, pre-vascularised tissue patches into rodents, the patches grew into cell grafts that were ten times larger than the too-small results from tissue composed of heart muscle cells only. The rodents were bred without an immune system that rejects tissue transplants.
Murry noted that these results have significance beyond their contribution to the ongoing search for ways to treat heart attack damage by regenerating heart tissue with stem cells.
The study findings, he observed, suggest that researchers consider including blood vessel-generating and vascular-supporting elements when designing human tissues for certain other types of regenerative therapies unrelated to heart disease.
One of the major obstacles still to be overcome is the likelihood that people's immune systems would reject the stem transplant unless they take medications for the rest of their lives to suppress this reaction. Murry hopes someday that scientists would be able to create new tissues from a person's own cells.
"Researchers can currently turn human skin cells back to stem cells, and then move them forward again into other types of cells, such as heart muscle and blood vessel cells," Murry said.
"We hope this will allow us to build tissues that the body will recognize as 'self.'"
While the clinical application of tissues engineered from stem cells in treating hearts damaged from heart attacks or birth defects is still in the future, the researchers believe progress has been made. This study showed that researchers could create the first entirely human heart tissue patch from human embryonic cell-derived heart muscle cells, blood vessel lining cells and fibre-producing cells, and successfully engraft the tissue into an animal.
Future studies will try to move heart cell regeneration closer toward clinical usefulness, according to Murry and his research team. They forecast that such research would include testing other sources of human cells and developing techniques to create bigger patches for treating larger animals through surgical transplantation or through catheter delivered injections.
Lastly, they concluded, researchers would need to test whether tissue patches actually improve physical functioning after implantation in damaged hearts.
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ZenMaster
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Enhanced Stem Cells Promote Tissue Regeneration
Enhanced Stem Cells Promote Tissue Regeneration Monday, 12 October 2009 Massachusetts Institute of Technology engineers have boosted stem cells' ability to regenerate vascular tissue (such as blood vessels) by equipping them with genes that produce extra growth factors (naturally occurring compounds that stimulate tissue growth). In a study in mice, the researchers found that the stem cells successfully generated blood vessels near the site of an injury, allowing damaged tissue to survive. Why it matters: Stem cells hold great potential as a way to promote tissue regeneration. However, this approach has been limited because stem cells don't produce enough growth factors after transplantation. The researchers' new super-charged stem cells could be used to treat an infarction (death of tissue caused by blockage of the blood supply, by a clot or another obstruction), or to induce blood supply for engineered tissues. Methods: After removing stem cells from mouse bone marrow, the researchers used specially developed nanoparticles to deliver the gene for the growth factor VEGF (vascular endothelial growth factor). The stem cells were then implanted into damaged tissue areas. These nanoparticles, which the MIT team has also tested to deliver cancer treatments, are believed to be safer than the viruses often used for gene delivery. Next steps: Though the results are promising, the technique needs more improvements before any human trials can begin, says Daniel Anderson, a senior author of the paper. ......... ZenMaster
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Human Embryonic Stem Cells Reverse Retinal Degeneration
Human Embryonic Stem Cells Reverse Retinal Degeneration Monday, 12 October 2009 A new study reports that transplanted pigment-containing visual cells derived from human embryonic stem cells (hESCs) successfully preserved structure and function of the specialized light-sensitive lining of the eye (known as the retina) in an animal model of retinal degeneration. The findings, published by Cell Press in the October 2nd issue of the journal Cell Stem Cell, represent an exciting step towards the future use of cell replacement therapies to treat devastating degenerative eye diseases that cause millions of people worldwide to lose their sight. The retinal pigment epithelium (RPE) is a layer of pigmented cells sandwiched between the visual retinal cells, called photoreceptors, and the nourishing blood vessels at the back of the eye. The RPE provides essential support to the retinal photoreceptors and is critical for normal vision. Deterioration of the RPE plays a central role in the progression of diseases such as age-related macular degeneration and sub-types of retinitis pigmentosa. These conditions are associated with a progressive loss of vision that often leads to blindness. "Although there are a variety of therapeutic approaches under development to delay the degenerative process, the grim reality is that many patients eventually lose their sight," explains Dr. Benjamin Reubinoff, a senior author of the study. "Cell therapy to replenish the degenerating RPE cells may potentially halt disease progression." Dr. Reubinoff and Dr. Eyal Banin who led the study, with their colleagues from Hadassah-Hebrew University Medical Center in Jerusalem, developed conditions to guide hESCs to differentiate into functional RPE-like cells in the laboratory. The researchers found that nicotinamide (vitamin B3, NIC) and Activin A, an important growth factor, promoted differentiation of hESCs towards an RPE fate. The hESC-derived RPE-like cells, which could be identified by their characteristic black pigment, exhibited multiple biological properties and genetic markers that define authentic RPE cells. Further, the cells successfully delayed deterioration of retinal structure and function when they were transplanted into an animal model of retinal degeneration caused by RPE dysfunction. Taken together, the results demonstrate that NIC and Activin A promoted the differentiation of hESCs towards an RPE fate. The hESC-derived cells exhibited the defining characteristics associated with RPE and successfully rescued the retina when transplanted into an animal model of retinal degeneration. "Our findings are an important step towards the potential future use of hESCs to replenish RPE in blinding diseases," concludes Dr. Banin. ......... ZenMaster
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Umbilical Cord Blood Source for Stem Cells
Readily Available and Patient-specific Stem Cells
Monday, 12 October 2009
Umbilical cord blood cells can successfully be reprogrammed to function like embryonic stem cells, setting the basis for the creation of a comprehensive bank of tissue-matched, cord blood-derived induced pluripotent stem (iPS) cells for off-the-shelf applications, report researchers at the Salk Institute for Biological Studies and the Center for Regenerative Medicine in Barcelona, Spain.
"Cord blood stem cells could serve as a safe, "ready-to-use" source for the generation of iPS cells, since they are easily accessible, immunologically immature and quick to return to an embryonic stem cell-like state," says Juan-Carlos Izpisúa Belmonte, Ph.D., a professor in the Salk's Gene Expression Laboratory, who led the study published in the October issue of the journal Cell Stem Cell.
Worldwide, there are already more than 400,000 cord blood units banked along with immunological information. Due to their early origin, cells found in umbilical cord blood contain a minimal number of somatic mutations and possess the immunological immaturity of newborn cells, allowing the HLA donor-recipient match to be less than perfect without the risk of immune rejection of the transplant.
Human leukocyte antigen (HLA) typing is used to match patients and donors for bone marrow or cord blood transplants. HLAs are special surface markers found on most cells in the body and help the immune system to distinguish between "self" and "non-self."
"Selecting common HLA haplotypes from among already banked cord blood units to create iPS cell would significantly reduce the number of cell lines needed to provide a HLA match for a large percentage of the population," says Izpisúa Belmonte.
"The population of cord blood cells used for reprogramming express reprogramming/stem cell factors at higher levels than those found in other adult somatic cells, which could explain why cord blood cells can be reprogrammed with less factors and in less time," says Izpisúa Belmonte.
"It's almost like they are already half-way there."
In addition, the cord blood-derived iPS cells, CBiPS cells for short, passed all standard tests for pluripotency: The gave rise to stem cell tumours known as teratomas and differentiated into derivatives of the three embryonic tissue layers, including rhythmically beating cardiomyocytes and dopamine-producing neurons.
Izpisúa Belmonte's next goal is to convince cord blood cells to burn back time using methods that are considered safe for clinical applications in humans. The original protocols for producing iPS cells — including the one used by Belmonte and his team — rely on the integration of foreign "reprogramming" genes into the host-cell genome, a process associated with risks including mutation and the development of cancers after iPS-cell transplantation, limiting their therapeutic value.
However, researchers are hard at work to develop alternative methods that allow them to reprogram cells without leaving any genetic traces, such as simply exposing differentiated cells to small molecules.
"Several studies have already shown that this could be possible," says Izpisúa Belmonte.
"If we can show they also work for cord blood cells, this certainly could be a step forward towards the clinical application of iPS cells. We should focus our efforts on this particular cell source, CBiPS cells, at least in the near future."
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The endodermal layer, identified by markers AFP and FoxA2, will give rise to the digestive tract, lungs and bladder. Credit: Courtesy of Juan-Carlos Izpisúa Belmonte, from Cell Stem Cell, Oct. 1, 2009.
Since the first adult cells were converted into iPS cells, they have generated a lot excitement as an uncontroversial alternative to embryonic stem cells and as a potential source for patient-specific stem cells. Unfortunately, taking a patient's cells back in time is not only costly, but could be difficult when those cells are needed right away to mend injured spinal cords or treat acute diseases, and outright impossible when the effects of aging or chronic disease have irrevocably damaged the pool of somatic cells.
"Patient-specific iPS lines have been advocated as a theoretically ideal clinical option to regenerate tissue but from a practical and cost-benefit aspect, this approach may not be feasible," says Izpisúa Belmonte. He hopes that the "large scale production and banking of cord blood-derived iPS lines in a publically available network could be a viable alternative for future clinical applications."
With this in mind, Belmonte and his colleagues set out to transform hematopoietic stem cells isolated from cord blood into iPS cells. They not only successfully converted them using only two out of the four most commonly used factors — Oct4 and Sox2 — but also in less time than any other previously published methodology require. No matter, whether the researchers started with freshly collected cord blood or previously frozen samples, the resulting iPS cells were indistinguishable from human embryonic stem cells.
The mesodermal layer, identified by ASM, will form bones, muscles, connective tissue and the middle layer of the skin. Credit: Courtesy of Juan-Carlos Izpisúa Belmonte , from Cell Stem Cell, Oct. 1, 2009.
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Human Cord Blood Cells Reprogrammed into Embryonic-like Stem Cells
Human Cord Blood Cells Reprogrammed into Embryonic-like Stem Cells Monday, 12 October 2009 Human umbilical cord blood cells may be far more versatile than previous research has indicated. Two independent studies, published by Cell Press in the October 2nd issue of the journal Cell Stem Cell, report that they have successfully reprogrammed human umbilical cord blood cells into cells with properties similar to human embryonic stem cells. The results are significant as they identify cord blood as a convenient source for generating cells with a theoretically limitless potential. Recent research has shown that adult cells can be reprogrammed into cells with characteristics similar to embryonic stem cells by turning on a select set of genes. The cells, called induced pluripotent stem (iPS) cells, have tremendous potential for regenerative medicine. However, issues related to difficulty harvesting adult cells, inefficient reprogramming and the accumulation of genetic errors (mutations) that may contribute to an increased risk for cancer and diminished cellular functionality have presented formidable challenges. Human umbilical cord blood cells have been suggested as an attractive alternative to adult cells for reprogramming. "Cord blood-derived cells can be collected without any risk for the donor, are young cells expected to carry minimal mutations and possess the immunological immaturity of newborn cells. We believe that cord blood cells could represent, rather than just another cell type that can be reprogrammed, a real alternative for a safer source of iPS cells," explains senior study author Dr. Izpisúa Belmonte from the Center of Regenerative Medicine in Barcelona, Spain and The Salk Institute in La Jolla, California. Dr. Izpisúa Belmonte and colleagues described a specific process that converted human cord blood cells into embryonic-like stem cells using only two factors. "From a mechanistic point of view, the fact that cord blood-derived iPS cells could be generated by activating only two genes is a crucial point that offers new possibilities for investigating the molecular basis of the reprogramming process," concludes Dr. Izpisúa Belmonte. In a separate study, led by Dr. Ulrich Martin from Hannover Medical School in Hannover, Germany, cord blood cells were also used to generate cells that exhibited characteristics typical of embryonic stem cells. Dr. Martin and colleagues demonstrated that the iPS cells had the potential to differentiate into multiple mature cell types, including functional heart muscle cells. "Our study provides a feasible strategy for the reproducible generation of iPS cells from human cord blood" offers Dr. Martin. "Importantly, public and commercial cord blood banks may provide a superior and almost unlimited source of for the production of clinically useful iPS cells." Both research groups highlight the substantial clinical convenience of the existing networks for banking human cord blood and the theoretical advantage of these "young" cells in that they may have a decreased risk of having accumulated damaging genetic mutations associated with adult cells. The successful reprogramming of human cord blood cells into pluripotent stem cells is an important step towards future regenerative therapies. "Our findings should facilitate the clinical translation of iPS cell-based therapies," says Dr. Izpisúa Belmonte. ......... ZenMaster
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Stem Cell Success Points to Way to Regenerate Parathyroid Glands
Embryonic stem cells provide model; goal is to prevent bone loss Monday, 12 October 2009 An early laboratory success is taking University of Michigan Health System researchers a step closer to parathyroid gland transplants that could one day prevent a currently untreatable form of bone loss associated with thyroid surgery. The scientists were able to induce embryonic stem cells to differentiate into parathyroid cells that produced a hormone essential to maintaining bone density. The laboratory results in live cell cultures, published in Stem Cells and Development, need to be tested in further pre-clinical studies. Parathyroid glands, four glands each the size of a rice grain that lie next to the thyroid in the neck, are easily damaged when surgeons operate on patients with cancerous or benign thyroid tumours. Without their calcium-regulating hormone, patients can develop osteomalacia, a severe form of bone loss similar to rickets that affects tens of thousands of people in the United States with muscle cramps and numbness in the hands and feet. "We used human embryonic stem cells as a model for ways to work out the recipe to make parathyroid cells," says Gerard M. Doherty, M.D., chief of endocrine surgery and Norman W. Thompson Professor of Endocrine Surgery at U-M Medical School. The research illustrates the payoff of rapidly increasing knowledge about how embryonic stem cells give rise to other kinds of cells. That knowledge can be the springboard for influencing other cells to regenerate damaged parts of the body. Doherty's team used embryonic stem cells from a Bush administration-approved embryonic stem cell line to test a way to produce functioning, differentiated parathyroid cells to transplant into a patient and restore function. With the recipe worked out, Doherty's team anticipates developing a treatment that does not use embryonic stem cells. "We anticipate taking a person's own cells and making them into parathyroid cells," Doherty says. Using the patient's own cells should eliminate the risk of rejection. What's next Having demonstrated a method for leading embryonic stem cells to produce parathyroid cells, the team hopes to be able to repeat those steps using cells from the patient's own thymus gland. The method involves no genetic modification of cells, a key goal of Doherty's team. "We want to have a process that will allow us to reintroduce cells into the patient's body safely," Doherty says. Any successful treatment in people is five to 10 years away. ......... ZenMaster
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