Stem cell research is a controversial issue that sharply divides people. There are two kinds of stem cell research: embryonic and adult. This distinction is imperative because of the ethical issues involved.

Embryonic stem cell research requires cells to be extracted from a human embryo. In the process of extracting the stem cells the embryo is destroyed and a life is ended. The embryonic stem cells are then isolated and theoretically coaxed into developing into just about any cell in the body. Embryonic stem cell transplants have not been shown concretely to have successfully helped a single patient.

Fetal tissue research requires the abortion of a living unborn child. The Center for Medical Progress, in a series of investigative videos (link to site), revealed that Planned Parenthoods affiliated clinics participate in the harvesting and sale of aborted baby body parts and placental tissue for financial gain. These are then used in research facilities around the country, including at Oregon Health and Science University. Fetal tissue research has also not successfully helped treat a single patient.

Adult stem cell research on the other hand, does not require the destruction of life. Adult stem cells are derived from sources like umbilical cords and organ tissue.

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Stem Cells, Fetal Tissue Research & Cloning - Oregon Right ...

Newswise BIRMINGHAM, Ala. Biomedical engineering researchers will attack two banes of cardiovascular disease heart failure after heart attacks and the scourge of resistant high blood pressure with $4.8 million in National Institutes of Health grants that begin this fall.

One sign of the clinical significance of this research by the University of Alabama at Birmingham investigators are the percentile scores that Jianyi Jay Zhang, M.D., Ph.D., and Gangjian Qin, M.D., received in those two NIH grant applications.

Zhangs plan to dissect the mechanisms of electromechanical integration of a human heart-muscle patch to aid survival and stability of the patch garnered a 1 percentile score, the highest possible. Qins plan to dissect a novel molecular pathway in endothelial cells of arteries that appears to regulate contractile function and blood pressure has significant potential to improve human health from the disease and death caused by high blood pressure, NIH reviewers said, and Qin received a 2 percentile score.

Zhang, chair and professor of the UAB Department of Biomedical Engineering and holder of the T. Michael and Gillian Goodrich Endowed Chair of Engineering Leadership, will receive $2.5 million over four years. Qin, professor of biomedical engineering and director of the Molecular Cardiology Program, will receive $2.3 million over four years.

Zhang came to UAB in 2015 from the University of Minnesota Medical School with the goal of moving his work with engineered heart patches into human use within seven years. As chair of Biomedical Engineering, a joint department of the UAB School of Medicine and the UAB School of Engineering, Zhang has recruited top researchers, and he also was awarded $11 million of NIH funding in 2016 $8 million of which is shared in collaborations with University of Wisconsin and Duke University researchers.

One of the recent recruits to biomedical engineering is Qin, who serendipitously discovered a novel and fascinating line of research that may lead to new drugs for treatment-resistant high blood pressure, where existing blood pressure drugs are ineffective. People with resistant high blood pressure have increased risk of strokes, heart attacks, heart failure and arterial aneurysms, and high blood pressure is a leading cause of chronic kidney failure. Even moderately elevated arterial blood pressure shortens life expectancy.

At the time, Qin was interested in the often fatal heart failure that occurs months or years after heart attacks. He reasoned that growth of new blood vessels into the damaged heart tissue of the left ventricle could be boosted by altering the amounts of cell-cycle regulators in the E2F family of transcription factors, to speed division of cells in the endothelial tissue of arteries.

When he deleted one of the eight E2Fs that are found in mice and humans E2F2 it had no effect on cell growth. But unexpectedly, we found a striking function, Qin said. If you delete E2F2, the vessel is more contractile. It becomes rigid and hard, and this contributes to high blood pressure.

So we had a question: How does E2F2 interact with other molecules to regulate blood pressure? Qin did pull-down experiments with E2F2, where other proteins are flowed past tethered E2F2 molecules to see if any would bind. He found that a kinase enzyme called Sam68 did bind to the transcription factor.

When he knocked out the gene for Sam68 in mice, they had low blood pressure.

Ultimately, a series of experiments in Qins lab and observations of other laboratories suggested a previously unknown mechanism of blood pressure control that involves E2F2/Sam68 and the expression of endothelial converting enzyme 1b. ECE-1b affects the levels of peptides that constrict blood vessels and raise blood pressure. Dysregulation of this pathway may contribute to blood pressure disorders, especially hypertension.

Despite a strong correlation, the E2F2/Sam68-ECE-1b pathway has not explicitly been linked to blood pressure regulation, and the mechanisms of how Sam68/E2F2 signaling regulates ECE-1b expression and blood vessel function remain uncharacterized.

Qin will use his new grant to search for the link to blood pressure regulation and characterize the mechanisms. His research could provide the missing links between the results of large-scale genomewide association studies of human high blood pressure and its pathogenesis namely how dysregulation leads to refractory hypertension.

Detailed knowledge of those steps would offer new targets for potential new drugs, which are especially needed to prevent or treat resistant hypertension.

Qin says he was attracted to UAB by the strong focus of clinicians and basic scientists on solving the clinical problem of hypertension, as well as the depth and breadth of cardiovascular disease research in biomedical engineering, the UAB Department of Pathology and the UAB Division of Cardiovascular Disease. He also has great interest in Zhangs research, where Qins past work in stem cell biology and cardiovascular science can contribute.

As measured by NIH funding, the UAB Department of Biomedical Engineering is the fourth-ranked biomedical engineering department among all departments that are jointly led by schools of medicine and engineering, according to the 2016 Blue Ridge NIH database.

The joint biomedical engineering departments ahead of UAB are at Stanford University, Johns Hopkins University, and Oregon Health and Science University. Those trailing UAB in the funding ranking are at the University of North Carolina-Chapel Hill, Emory University, University of Virginia, Case Western Reserve University, University of Colorado-Denver, University of Rochester, the University of Illinois-Chicago, Wake Forest University Health Sciences and State University of New York-Stony Brook.

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New Biomedical Engineering Grants Aim at Heart Failure and Resistant High Blood Pressure - Newswise (press release)

Deadly gene mutations removed from human embryos in landmark study, reports The Guardian. Researchers have used a gene-editing technique to repair faults in DNA that can cause an often-fatal heart condition called hypertrophic cardiomyopathy.

This inherited heart condition is caused by a genetic change (mutation) in one or more genes. Babies born with hypertrophic cardiomyopathy have diseased and stiff heart muscles, which can lead to sudden unexpected death in childhood and in young athletes.

In this latest study researchers used a technique called CRISPR-cas9 to target and then remove faulty genes. CRISPR-cas9 acts like a pair of molecular scissors, allowing scientists to cut out certain sections of DNA. The technique has attracted a great deal of excitement in the scientific community since it was released in 2014. But as yet, there have been no practical applications for human health.

The research is at an early stage and cannot legally be used as treatment to help families affected by hypertrophic cardiomyopathy. And none of the modified embryos were implanted in the womb.

While the technique showed a high degree of accuracy, its unclear whether it is safe enough to be developed as a treatment. The sperm used in the study came from just one man with faulty genes, so the study needs to be repeated using cells from other people, to be sure that the findings can be replicated.

Scientists say it is now important for society to start a discussion about the ethical and legal implications of the technology. It is currently against the law to implant genetically altered human embryos to create a pregnancy, although such embryos can be developed for research.

The study was carried out by researchers from Oregon Health and Science University and the Salk Institute for Biological Studies in the US, the Institute for Basic Science and Seoul University in Korea, and BGI-Shenzen and BGI-Quingdao in China. It was funded by Oregon Health and Science University, the Institute for Basic Science, the G. Harold and Leila Y. Mathers Charitable Foundation, the Moxie Foundation and the Leona M. and HarryB. Helmsley Charitable Trust and the Shenzhen Municipal Government of China. The study was published in the peer-reviewed journal Nature.

The Guardian carried a clear and accurate report of the study. While their reports were mostly accurate, ITV News, Sky News and The Independent over-stated the current stage of research, with Sky News and ITV News saying it could eradicate thousands of inherited conditions and the Independent claiming it opens the possibility for inherited diseases to be wiped out entirely. While this may be possible, we dont know whether other inherited diseases might be as easily targeted as this gene mutation.

Finally, the Daily Mail rolls out the arguably tired clich of the technique leading to designer babies, which seems irrelevant at this point. The CRISPR-cas9 technique is only in its infancy and (ethics aside) its simply not possible to use genetic editing to select desirable characteristics - most of which are not the result of one single, identifiable gene. No reputable scientist would attempt such a procedure.

This was a series of experiments carried out in laboratories, to test the effects of the CRISPR-Cas9 technique on human cells and embryos. This type of scientific research helps us understand more about genes and how they can be changed by technology. It doesnt tell us what the effects would be if this was used as a treatment.

Researchers carried out a series of experiments on human cells, using the CRISPR-cas9 technique first on modified skin cells, then on very early embryos, and then on eggs at the point of fertilisation by sperm. They used genetic sequencing and analysis to assess the effects of these different experiments on cells and how they developed, up to five days. They looked specifically to see what proportion of cells carrying faulty mutations could be repaired, whether the process caused other unwanted mutations, and whether the process repaired all cells in an embryo, or just some of them.

They used skin cells (which were modified into stem cells) and sperm from one man, who carried the MYBPC3 mutation in his genome, and donor eggs from women without the genetic mutation. This is the mutation known to cause hypertrophic cardiomyopathy.

Normally in such cases, roughly half the embryos would have the mutation and half would not, as theres a 50-50 chance of the embryo inheriting the male or female version of the gene.

The CRISPR-cas9 technique can be used to select and delete specific genes from a strand of DNA. When this happens, usually the cut ends of the strand join together, but this causes problems so cant be used in the treatment of humans. The scientists created a genetic template of the healthy version of the gene, which they introduced at the same time as using CRISPR-cas9 to cut the mutated gene. They hoped the DNA would repair itself with a healthy version of the gene.

One important problem with changing genetic material is the development of mosaic embryos, where some of the cells have corrected genetic material and others have the original faulty gene. If that happened, doctors would not be able to tell whether or not an embryo was healthy.

The scientists needed to test all the cells in the embryos produced in the experiment, to see whether all cells had the corrected gene or whether the technique had resulted in a mixture. They also did whole genome sequencing on some embryos, to test for unrelated genetic changes that might have been introduced accidentally during the process.

All embryos in the study were destroyed, in line with legislation about genetic research on embryos.

Researchers found that the technique worked on some of the stem cells and embryos, but worked best when used at the point of fertilisation of the egg. There were important differences between the way the repair worked on the stem cells and the egg.

Only 28% of the stem cells were affected by the CRISPR-cas9 technique. Of these, most repaired themselves by joining the ends together, and only 41% were repaired by using a corrected version of the gene.

67% of the embryos exposed to CRISPR-cas9 had only the correct version of the gene higher than the 50% that would have been expected had the technique not been used. 33% of embryos had the mutated version of the gene, either in some or all their cells.

Importantly, the embryos didnt seem to use the template injected into the zygote to carry out the repair, in the way the stem cells did. They used the female version of the healthy gene to carry out the repair, instead.

Of the embryos created using CRISPR-cas9 at the point of fertilisation, 72% had the correct version of the gene in all their cells, and 28% had the mutated version of the gene in all their cells. No embryos were mosaic a mixture of cells with different genomes.

The researchers found no evidence of mutations induced by the technique, when they examined the cells using a variety of techniques. However, they did find some evidence of gene deletions caused by DNA strands splicing (joining) themselves together without repairing the faulty gene.

The researchers say they have demonstrated how human embryos employ a different DNA damage repair system to adult stem cells, which can be used to repair breaks in DNA made using the CRISPR-cas9 gene-editing technique.

They say that targeted gene correction could potentially rescue a substantial portion of mutant human embryos, and increase the numbers available for transfer for couples using pre-implantation diagnosis during IVF treatment.

However, they caution that despite remarkable targeting efficiency, CRISPR-cas9-treated embryos would not currently be suitable for transfer. Genome editing approaches must be further optimised before clinical application can be considered, they say.

Currently, genetically-inherited conditions like hypertrophic cardiomyopathy cannot be cured, only managed to reduce the risk of sudden cardiac death. For couples where one partner carries the mutated gene, the only option to avoid passing it on to their children is pre-implantation genetic diagnosis. This involves using IVF to create embryos, then testing a cell of the embryo to see whether it carries the healthy or mutated version of the gene. Embryos with healthy versions of the gene are then selected for implantation in the womb.

Problems arise if too few or none of the embryos have the correct version of the gene. The researchers suggest their technique could be used to increase the numbers of suitable embryos. However, the research is still at an early stage and has not yet been shown to be safe or effective enough to be considered as a treatment.

The other major factor is ethics and the law. Some people worry that gene editing could lead to designer babies, where couples use the tool to select attributes like hair colour, or even intelligence. At present, gene editing could not do this. Most of our characteristics, especially something as complex as intelligence, are not the result of one single, identifiable gene, so could not be selected in this way. And its likely that, even if gene editing treatments became legally available, they would be restricted to medical conditions.

Designer babies aside, society needs to consider what is acceptable in terms of editing human genetic material in embryos. Some people think that this type of technique is "playing God" or is ethically unacceptable because it involves discarding embryos that carry faulty genes. Others think that its rational to use the scientific techniques we have developed to eliminate causes of suffering, such as inherited diseases.

This research shows that the questions of how we want to legislate for this type of technique are becoming pressing. While the technology is not there yet, it is advancing fast. This research shows just how close we are getting to making genetic editing of human embryos a reality.

Excerpt from:
Gene editing used to repair diseased genes in embryos - NHSUK - NHS Choices