Wednesday, March 1, 2017 6:01 AM UTC

PRESS RELEASE

TiGenix to present at Cowen's 37thAnnual Health Care Conference in Boston

Leuven (BELGIUM) - 1st March, 2017, 07:00h CET - TiGenix NV (Euronext Brussels and Nasdaq: TIG), an advanced biopharmaceutical company focused on developing and commercializing novel therapeutics from its proprietary platforms of allogeneic expanded stem cells, today announced that Eduardo Bravo, CEO of TiGenix, will be presenting at the 37th Annual Cowen and Company's Health Care Conference in Boston (USA) at The Boston Marriott Copley Place on Monday, March 6 at 3:20-3:50PM (EST) in Regis, 3rd Floor (breakout at 4:00 PM-04:30PM (EST) at Boston University, 3rd Floor).

The presentation will be webcast live and can be accessed on the day of the event at this link. A replay of the webcast will be available on the Company's website for 30 days following the presentation. To ensure timely connection, it is recommended that users register at least 10 minutes prior to the scheduled webcast.

The TiGenix management team will be available for one-to-one meetings from Monday, March 6th to Wednesday, March 8th. Please contact Investor Relations at Investor@tigenix.com for a meeting request.

For more information:

Claudia D'Augusta Chief Financial Officer T: +34 91 804 92 64 claudia.daugusta@tigenix.com

About TiGenix

TiGenix NV (Euronext Brussels: TIG) is an advanced biopharmaceutical company focused on developing and commercializing novel therapeutics from its proprietary platforms of allogeneic, or donor-derived, expanded stem cells. Our lead product candidate from the adipose-derived stem cell technology platform is Cx601, which is in registration with the European Medicines Agency for the treatment of complex perianal fistulas in Crohn's disease patients. Our adipose-derived stem cell product candidate Cx611 has completed a Phase I sepsis challenge trial and a Phase I/II trial in rheumatoid arthritis. Effective July 31, 2015, TiGenix acquired Coretherapix, whose lead cellular product candidate, AlloCSC-01, is currently in a Phase II clinical trial in Acute Myocardial Infarction (AMI). In addition, the second product candidate from the cardiac stem cell-based platform acquired from Coretherapix, AlloCSC-02, is being developed in a chronic indication. On July 4, 2016, TiGenix entered into a licensing agreement with Takeda, a large pharmaceutical company active in gastroenterology, under which Takeda acquired the exclusive right to commercialize Cx601 for complex perianal fistulas outside the United States. TiGenix is headquartered in Leuven (Belgium) and has operations in Madrid (Spain).

About Cx601

Cx601 is a suspension of allogeneic expanded adipose-derived stem cells (eASC) locally injected. Cx601 is an investigational agent being developed for the treatment of complex perianal fistulas in Crohn's disease patients with inadequate response to at least one conventional or biologic therapy including antibiotics, immunosuppressants, or anti-TNF agents. Crohn's disease is a chronic inflammatory disease of the intestine and patients can suffer from complex perianal fistulas for which there is currently no effective treatment. In 2009, the European Commission granted Cx601 orphan designation for the treatment of anal fistulas, recognizing the debilitating nature of the disease and the lack of treatment options. Cx601 has met the primary end-point in the Phase III ADMIRE-CD study in Crohn's disease patients with complex perianal fistula, a randomized, double-blind, placebo-controlled trial run in Europe and Israel and designed to comply with the requirements laid down by the EMA. 'Madrid Network' issued a soft loan to help finance this Phase III study, which was funded by the Secretary of State for Research, Development and Innovation (Ministry of Economy and Competitiveness) within the framework of the INNTEGRA plan. The study's primary endpoint was combined remission, defined as clinical assessment at week 24 of closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections >2cm confirmed by MRI. In the ITT population (n=212), Cx601 achieved statistically significant superiority (p=0.024) on the primary endpoint with 50% combined remission at week 24 compared to 34% in the placebo arm. Efficacy results were robust and consistent across all statistical populations. Treatment emergent adverse events (non-serious and serious) and discontinuations due to adverse events were comparable between Cx601 and placebo arms. The 24-weeks results have been published by The Lancet, one of the most highly regarded and well known medical journals in the world. The Phase III study has completed a follow-up analysis at 52 weeks confirming its sustained efficacy and safety profile. Top line follow-up data showed that in the ITT population Cx601 achieved statistical superiority (p=0.012) with 54% combined remission at week 52 compared to 37% in the placebo arm. The 52-week data also showed a higher rate of sustained closure in those patients treated with Cx601 and in combined remission at week 24 (75.0%) compared to patients in the placebo group (55.9%). Based on the positive 24-weeks Phase III study results, TiGenix has submitted a Marketing Authorization Application to the EMA in early 2016. TiGenix is preparing to develop Cx601 in the U.S. after having reached an agreement with the FDA through a special protocol assessment procedure (SPA) in 2015. On July 4, 2016 TiGenix entered into a licensing agreement with Takeda, a pharmaceutical company leader in gastroenterology, whereby Takeda acquired an exclusive right to commercialize Cx601 for complex perianal fistulas in Crohn's patients outside of the U.S.

Forward-looking information

This press release may contain forward-looking statements and estimates with respect to the anticipated future performance of TiGenix and the market in which it operates. Certain of these statements, forecasts and estimates can be recognised by the use of words such as, without limitation, "believes", "anticipates", "expects", "intends", "plans", "seeks", "estimates", "may", "will" and "continue" and similar expressions. They include all matters that are not historical facts. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may depend upon factors that are beyond the Company's control. Therefore, actual results, the financial condition, performance or achievements of TiGenix, or industry results, may turn out to be materially different from any future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of the publication of this press release. TiGenix disclaims any obligation to update any such forward-looking statement, forecast or estimates to reflect any change in the Company's expectations with regard thereto, or any change in events, conditions or circumstances on which any such statement, forecast or estimate is based, except to the extent required by Belgian law.

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TiGenix to present at Cowen's 37th Annual Health Care Conference in Boston - EconoTimes

Cardiac Stem Cells Comments Off on TiGenix to present at Cowen’s 37th Annual Health Care Conference in Boston – EconoTimes | March 1st, 2017

Karaikal, Feb 28 (PTI) Recent advancements in stem cells research have given hope for successfully treating diabetic heart disease (DHD), renowned New Zealand-based researcher in cardiovascular diseases Dr Rajesh Katare said today.

DHD affected the muscular tissues of the heart leading to complications and it had been demonstrated that resident stem cells of myocardium can be stimulated to repair and replace e degenerated cardiac myocytes resulting in a novel therapeutic effect and ultimately cardiac regeneration, he said.

Katare, Director of Cardiovascular Research Division in the University of Otago, New Zealand, was delivering the keynote address at the continuing medical education programme on Role of Micro-RNAs and stem cells in cardiac regeneration in diabetic heart disease at the Karaikal campus of premier health institute JIPMER.

Presenting clinical evidences, Katare said stem cell therapy certainly presented a new hope for successfully treating DHD.

Jawaharlal Institute of Post Graduate Medical Education (JIPMER) Director Dr Subash Chandra Parija pointed out that it was the first such programme on the role of stem cells in cardiac regeneration in the whole of the country.

He said as diabetes was highly prevalent in the country, providing treatment for DHD had become a big challenge.

Patients suffering from the condition have to undergo lifelong treatment and medications. In this backdrop, advancements in stem cell therapy assume significance, he said.

This is published unedited from the PTI feed.

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Stem cell therapy can help in treating diabetic heart disease - India.com

Cardiac Stem Cells Comments Off on Stem cell therapy can help in treating diabetic heart disease – India.com | February 28th, 2017

GETTY

A high-level meeting has paved the way for global trials to begin on hundreds of patients.

British scientists have found a way to use stem cells to repair damaged tissue which could help millions living with heart failure, the UKs leading cause of death.

Scarring due to disease or heart attacks affects more than two million people in Britain.

This would be the biggest breakthrough since the first transplants three decades ago

Professor Steve Westaby

Initial trials involving more than 100 patients are being planned for the autumn at two London hospitals.

World renowned cardiac surgeon Professor Steve Westaby, who helped pioneer the revolutionary technique, said it had been thought that repairing heart damage was impossible.

But results from a long-term trial that began in Greece five years ago have shown that this is not the case.

Preliminary data from this trial showed the engineered stem cells, known as Heartcel, can reverse scarring by up to 79 per cent.

The data, presented at the European Society of Cell and Gene Therapy in Florence, showed an average of 40 per cent reduction in heart damage in those on the treatment.

Last month researchers finalised talks with European and US regulators to discuss the timetable for global trials next year involving 500 people.

Getty

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6 early signs of a heart attack

Professor Westaby, from the John Radcliffe Hospital, Oxford, said: I am very excited at the prospect of a trial which will hopefully lead to the availability of this stem cell treatment to thousands of patients annually in the UK.

Other scientists have tried in vain to repair damaged heart muscle using stem cells over the past few decades.

This is the first time scarring has been shown to be reversible. It could herald an end to transplants and lead to a treatment for heart failure within three to five years.

GETTY

Professor Westaby said: This would be the biggest breakthrough since the first transplants three decades ago.

Professor Westaby has been working on the technique for more than a decade and is carrying out the study with Professor Kim Fox, head of the National Heart and Lung Institute, at Imperial College London.

The implanted stem cells were created by medical outfit Celixir, co-founded by Nobel laureate Professor Martin Evans, the first scientist to culture mice embryonic stem cells in a laboratory.

Professor Westaby was inspired to work on the breakthrough in 1999 after a four-month-old baby girls heart healed itself after he carried out a major life-saving operation.

Kirsty Collier, from Swindon, was dying of a serious and rare heart defect. In a last ditch effort Professor Westaby cut away a third of her badly damaged heart.

GETTY

GETTY

Surprisingly it began to beat. Fourteen years later a scan has shown that the heart had healed itself.

Now Kirsty, 18, has a normal one. Professor Westaby said: She was essentially dead and was only resurrected by what I regarded at the time as a completely bizarre operation.

The fact there was no sign of heart damage told me there were foetal stem cells in babies hearts that could remove scarring of heart muscle. That never happens in adults.

Its all down to the clues we got from Kirstys operation.

Read more here:
Heart failure BREAKTHROUGH: Stem cells trial offers hope to millions - Express.co.uk

Cardiac Stem Cells Comments Off on Heart failure BREAKTHROUGH: Stem cells trial offers hope to millions – Express.co.uk | February 25th, 2017

Dr. Jeffrey Spees, an associate professor of medicine at the University of Vermonts College of Medicine, will present Rescue and Repair of Cardiac Tissue After Injury: Turning Star Trek into Sesame Street, on Wednesday, March 1, at the Town and Country Resort, 876 Mountain Road, Stowe. Doors open at 1 p.m. and the lecture begins promptly at 1:30 p.m. This is the eighth Osher Lifelong Learning Institute lecture of the winter series.

Spees earned his Ph.D. in physiological and molecular ecology at the University of California, Davis. At UVM he teaches courses in developmental neurobiology, human structure and function and stem cells and regenerative medicine.

Spees has directed the Stem Cell Core in UVMs Department of Medicine and was one of the founding members of the New England Stem Cell Consortium. Spees and his colleagues have developed and applied for a patent for a therapy using a protein complex that is highly protective and keeps cells alive. He will discuss this research and its role in repairing cardiac tissue to improve cardiac function after a heart attack.

Vermont musicologist Joel Najman will present the final lecture of the winter series, Rock n Roll: From Elvis to Lady Gaga, on Wednesday, March 8.

The lecture is $5 and refreshments will be served after the talk. To check on weather cancellations, listen to WDEV 550 AM or WLVB 93.9 FM or call Town and Country Resort at 253-7595. To sponsor a lecture, a series or refreshments, call Dick Johannesen, 253-8475. Information: learn.uvm.edu/osher.

Read more here:
Cardiac injury, recovery is topic of Osher lecture - Stowe Today

Cardiac Stem Cells Comments Off on Cardiac injury, recovery is topic of Osher lecture – Stowe Today | February 25th, 2017

Cells within our bodies divide and change over time, with thousands of chemical reactions occurring within each cell daily. This makes it difficult for scientists to understand whats happening inside. New nanostraws offer a non-disruptive way to find out.

A problem with the current method of cell sampling, called lysing, is that it ruptures the cell. Once the cell is destroyed, it cant be sampled from again. This new sampling system relies on tiny tubes 600 times smaller than a strand of hair that allow researchers to sample a single cell at a time. The nanostraws penetrate a cells outer membrane, without damaging it, and draw out proteins and genetic material from the cells salty interior.

Its like a blood draw for the cell, says Nicholas Melosh, an associate professor of materials science and engineering at Stanford University and senior author of a paper describing the work in the Proceedings of the National Academy of Sciences.

The nanostraw sampling technique, according to Melosh, will significantly impact our understanding of cell development and could lead to much safer and effective medical therapies because the technique allows for long term, non-destructive monitoring.

What we hope to do, using this technology, is to watch as these cells change over time and be able to infer how different environmental conditions and chemical cocktails influence their developmentto help optimize the therapy process, Melosh says.

If researchers can fully understand how a cell works, then they can develop treatments that will address those processes directly. For example, in the case of stem cells, researchers are uncovering ways of growing entire, patient-specific organs. The trick is, scientists dont really know how stem cells develop.

For stem cells, we know that they can turn into many other cell types, but we do not know the evolutionhow do they go from stem cells to, say, cardiac cells? There is always a mystery. This sampling technique will give us a clearer idea of how its done, says Yuhong Cao, a graduate student and first author on the paper.

The sampling technique could also inform cancer treatments and answer questions about why some cancer cells are resistant to chemotherapy while others are not.

With chemotherapy, there are always cells that are resistant, says Cao. If we can follow the intercellular mechanism of the surviving cells, we can know, genetically, its response to the drug.

The sampling platform on which the nanostraws are grown is tinyabout the size of a gumball. Its called the Nanostraw Extraction (NEX) sampling system, and it was designed to mimic biology itself.

In our bodies, cells are connected by a system of gates through which they send each other nutrients and molecules, like rooms in a house connected by doorways. These intercellular gates, called gap junctions, are what inspired Melosh six years ago, when he was trying to determine a non-destructive way of delivering substances, like DNA or medicines, inside cells. The new NEX sampling system is the reverse, observing whats happening within rather than delivering something new.

Its a super exciting time for nanotechnology, Melosh says. Were really getting to a scale where what we can make controllably is the same size as biological systems.

Building the NEX sampling system took years to perfect. Not only did Melosh and his team need to ensure cell sampling with this method was possible, they needed to see that the samples were actually a reliable measure of the cell content, and that samples, when taken over time, remained consistent.

When the team compared their cell samples from the NEX with cell samples taken by breaking the cells open, they found that 90 percent of the samples were congruous. Meloshs team also found that when they sampled from a group of cells day after day, certain molecules that should be present at constant levels remained the same, indicating that their sampling accurately reflected the cells interior.

With help from collaborators Sergiu P. Pasca, assistant professor of psychiatry and behavioral sciences, and Joseph Wu, professor of radiology, Melosh and coworkers tested the NEX sampling method not only with generic cell lines, but also with human heart tissue and brain cells grown from stem cells. In each case, the nanostraw sampling reflected the same cellular contents as lysing the cells.

The goal of developing this technology, according to Melosh, was to make an impact in medical biology by providing a platform that any lab could build. Only a few labs across the globe, so far, are employing nanostraws in cellular research, but Melosh expects that number to grow dramatically.

We want as many people to use this technology as possible, he says.

Funding for the work came from the National Institute of Standards and Technology, the Knut and Alice Wallenberg Foundation, the National Institutes of Health, Stanford Bio-X, the Progenitor Cell Biology Consortium, the National Institute of Mental Health, an MQ Fellow award, the Donald E. and Delia B. Baxter Foundation, and the Child Health Research Institute.

Source: Jackie Flynn forStanford University

Read the original:
Nanostraw doesn't destroy cells as it samples their guts - Futurity: Research News

Cardiac Stem Cells Comments Off on Nanostraw doesn’t destroy cells as it samples their guts – Futurity: Research News | February 23rd, 2017

The decade-old excitement surrounding the potential for autologous cell therapy to treat cardiovascular disease may have fizzled into futility for many clinicians. But according to a new European consensus document, its possible this technology will yet find a way into future practice .

One of the problems the field has faced is that people got super excited 10 years ago because it was overhyped, and essentially . . . it led to the expectation that every time we presented [something] at clinical meetings, the field would move forward. And of course that wasnt the case, chair of the European Society of Cardiology stem cell task force and lead author Anthony Mathur, MD (St Bartholomews Hospital West Smithfield, London, England), told TCTMD.

The reason why I think people have run out of steam on this one is that theyve shared the 10-year journey with us. Anthony Mathur

Mathur contrasted the story of cell therapy to that of drug or device development, which is usually kept private until promising phase III data are available to support its routine use. What we've done is weve exposed the clinical and scientific community to a journey that in pharma we just wouldn't see as clinicians, he said. The reason why I think people have run out of steam on this one is that theyve shared the 10-year journey with us.

The document, which appeared online February 15, 2017, ahead of print in the European Heart Journal, was written as an update to a slightly more optimistic statement from the same task force published in 2006.

Of all of the recommendations that the original document made, very few have borne fruit. For example, the task force suggested the completion of a randomized trial for the use of autologous stem cells to treat acute MI patients presenting after more than 12 hours or who fail to respond to therapy. A trial such as this has not been undertaken and likely wont happen, given that primary angioplasty practice in Europe and the United States has revolutionized the treatment of acute MI and drastically lowered mortality, Mathur said. Any new method of treating acute MI will find it really tough to demonstrate an improvement unless its a complete game changer.

Since these patients may well develop heart failure, for which chronic cell therapy strategies are under development, research efforts should refocus there for now, the task force writes.

However, they stand by one 2006 recommendation for a randomized trial of autologous cells in acute MI patients presenting within 12 hours and treated with immediate revascularization. The ongoing phase III BAMI trial, undertaken by members of this task force including Mathur, will study just that but results are not expected for several years. Once these results are available, it will be time to either draw a line under it or ask for regulatory approval, but it's sort of pointless to keep rehashing the whole thing and going back asking the same question, Mathur said.

Careful But Hopeful

Looking back, Mathur said that the trajectory of cell therapy in cardiology has taught him to be self-critical and very careful about what we say, and to understand that it is okay to stop doing certain things that were once thought to be appropriate. Also, because those involved in translational research lack the tools that give us an evidence or an idea of the signal that we should expect in larger clinical trials, [a] lot of what weve come across is potentially unexpected. Unfortunately, it also means . . . weve probably disregarded areas of research based on the signals we haven't seen in smaller studies simply because, in a way, the tools we have arent sensitive enough to pick it up, he said.

If there is any biological signal found in a phase II study, Mathur stressed the importance of trying to complete a phase III study in order to unlock these unexpected kernels.

Far from being defeated, he said he is hopeful that cell therapy will pan out in some way for cardiac patients. Whether cell therapy worked or not, it's all about the amazing stories and how it changed people's lives seemingly for the better. So thats something thats difficult to drop, Mathur said. We have seen a signal for patients in heart failure in which there seems to be some sort of benefit. And some might say its purely psychological. Fine, but these people who were told there was nothing else that could be done got better.

The rest is here:
Less Acute MI, More HF: European Task Force Shifts Support for 'Overhyped' Cell Therapy Research - TCTMD

Cardiac Stem Cells Comments Off on Less Acute MI, More HF: European Task Force Shifts Support for ‘Overhyped’ Cell Therapy Research – TCTMD | February 23rd, 2017

Tiny nanostraws may offer a glimpse into a cells contents without causing any damage to the cell.

The nanostraws were developed by researchers at Stanford University, who devised a method of sampling cell contents without disrupting its natural processes, which is a staple of current cell sampling methods.

The new method relies on tiny tubes 600 times smaller than a stand of hair that allow researchers to sample a single cell at a time. The nanostraws are able to penetrate a cells outer membrane without damaging it and draw out proteins and genetic material from the cells salty interior.

It's like a blood draw for the cell, Nicholas Melosh, an associate professor of materials science and engineering and senior author on a paper, said in a statement.

According to Melosh, this technique will significantly impact the understanding of cell development and could yield much safer and effective medical therapies because it allows for long term, non-destructive monitoring.

What we hope to do, using this technology, is to watch as these cells change over time and be able to infer how different environmental conditions and 'chemical cocktails' influence their developmentto help optimize the therapy process, he said.

If researchers gain a better grasp on how a cell works they can address those processes directly.

For stem cells, we know that they can turn into many other cell types but we do not know the evolutionhow do they go from stem cells to, say, cardiac cells? Yuhong Cao, a graduate student and first author on the paper, said in a statement. This sampling technique will give us a clearer idea of how it's done.

A benefit of the sampling method is it could inform cancer treatments and answer questions about why some cancer cells are resistant to chemotherapy while others are not.

With chemotherapy, there are always cells that are resistant, Cao said. If we can follow the intercellular mechanism of the surviving cells, we can know, genetically, its response to the drug.

The nanostraws are grown in a small sampling platform designed to mimic biology called the Nanostraw Extraction (NEX) sampling system.

Cells divide and change over time, with thousands of chemical reactions occurring within each cell every day, which makes it difficult to truly understand the inner workings of cells.

Currently, scientists use a method of cell sampling called lysing, which ruptures the cell. However, once a cell is destroyed it cannot be sampled from again.

Cells in our bodies are connected by a system of gates through which they send each other nutrients and molecules.

Melosh was inspired to develop the new system when he observed the intercellular gates after he was trying to determine a non-destructive way of delivering substances, including DNA or medicines, inside cells.

The new sampling system is the reverse of that process, as scientists are able to observe whats happening within a cell.

When the research team compared their cells samples from the NEX with cell samples taken by breaking the cells open, they found that 95 percent of the samples were congruous.

The team also found that when they sampled from a group of cells day after day, certain molecules that should be present at constant levels remained the same, which indicated that their sampling accurately reflected the cells interior.

The team not only sampled generic cell lines but also with human heart tissue and brain cells grown from stem cells and in each case the nanostraw sampling reflected the same cellular contents as lysing the cells.

The study was published in the Proceedings of the National Academy of Sciences of the United States of America.

Read the rest here:
Nanostraws Sample Cells Without Damage - R & D Magazine

Cardiac Stem Cells Comments Off on Nanostraws Sample Cells Without Damage – R & D Magazine | February 23rd, 2017

Science Daily

Researchers implicate suspect in heart disease linked to diabetes ... Science Daily Scientists have struggled to trace the specific biology behind diabetes-associated heart disease risk or find ways to intervene. Now, researchers have hunted ... and more »

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Researchers implicate suspect in heart disease linked to diabetes ... - Science Daily

Cardiac Stem Cells Comments Off on Researchers implicate suspect in heart disease linked to diabetes … – Science Daily | February 22nd, 2017

February 21, 2017 by Mark Derewicz Top Row: Heart arteries in normal mice, diabetic mice, and normal mice with deleted IRS-1 gene. Bottom row: when artery is wounded, diabetic mice with less IRS-1 and normal mice with deleted IRS-1 gene show much greater blockage due to over-proliferation of smooth muscle cells. Credit: Clemmons Lab, UNC School of Medicine

People with diabetes are at high risk of developing heart disease. Despite knowing this, scientists have struggled to trace the specific biology behind that risk or find ways to intervene. Now, UNC School of Medicine researchers have hunted down a possible culprit - a protein called IRS-1, which is crucial for the smooth muscle cells that make up veins and arteries.

According to a study published in the Journal of Biological Chemistry, too little of IRS-1 causes cells to revert to a "dedifferentiated" or stem-cell like state, and this may contribute to the buildup of plaque in the heart's arteries, a condition known as atherosclerosis, which increases the risk of heart attack, stroke, and other forms of heart disease.

"When diabetes is poorly managed, your blood sugar goes up and the amount of this protein goes down, so the cells become subject to abnormal proliferation," said senior author David R. Clemmons, MD, Sarah Graham Kenan Professor of Medicine at the UNC School of Medicine. "We need to conduct more studies, but we think this cell pathway may have significant implications for how high blood glucose leads to atherosclerosis in humans."

The research could bring scientists one step closer to finding drugs to help stave off heart disease in people with diabetes, who are twice as likely to have heart disease or experience a stroke, as compared to people without diabetes. People with diabetes also tend to experience major cardiac events at a younger age.

The study focused on the cells that form the walls of veins and arteries, known as vascular smooth muscle cells. The main function of these cells is to contract whenever the heart beats, helping to push oxygen-rich blood to the body's tissues. When plaque builds up along the arterial walls, these cells gradually lose their ability to contract.

In their previous work, Clemmons and colleagues discovered that diabetes can trigger an abnormal cell signaling pathway that causes vascular smooth muscle cells to proliferate, which contributes to atherosclerosis. But their attempts to correct the abnormal signaling pathway didn't seem to completely solve the problem, leading them to suspect another factor.

In the new study, the team found that IRS-1 acts as an inhibitor of the abnormal signaling pathway thereby keeping the vascular smooth muscle cells differentiated, or specialized. In the absence of IRS-1, the cells revert to a stem-cell like state, which in turn activates the abnormal signaling pathway and promotes cell proliferation.

In people with diabetes, the presence of IRS-1 is strongly influenced by how well - or how poorly - blood sugar is kept in check. Previous studies have shown that patients who frequently or consistently have high blood sugar show dramatic reductions in IRS-1. The new study is the first to link this reduction with a predisposition for heart disease.

"The study suggests that you can't just inhibit the abnormal signaling, which we've already figured out how to do," Clemmons said. "Our work suggests you probably have to restore the normal signaling pathway, at least to some extent, in order to completely restore the cells to normal cell health, differentiation, and functioning."

As a next step, the Clemmons lab will look for things that might stimulate the synthesis of this protein even in the presence of high blood glucose.

To prove that IRS-1 acts as a brake on the abnormal signaling pathway that leads to cell proliferation, the team conducted experiments in three different types of mice: healthy mice, diabetic mice, and nondiabetic mice that were genetically engineered to produce no IRS-1. The scientists made a small incision in the blood vessels of the animals and then watched to see how the vascular smooth muscle cells reacted. In healthy mice, the incision stimulated wound healing but little cellular proliferation. In both the diabetic animals and the nondiabetic IRS-1 deficient animals, the researchers observed a marked increase in abnormal cellular proliferation.

The findings suggest that it may be possible to counteract the deleterious effects of high blood sugar on atherosclerosis by developing drugs that boost IRS-1.

Clemmons said the activities of IRS-1 might also play a role in other diabetes complications, such as eye and kidney disease. The researchers plan to study those potential links.

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People with diabetes are at high risk of developing heart disease. Despite knowing this, scientists have struggled to trace the specific biology behind that risk or find ways to intervene. Now, UNC School of Medicine researchers ...

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I was diagnosed with type 2 Diabetes and put on Metformin on June 26th, 2016. I started the ADA diet and followed it 100% for a few weeks and could not get my blood sugar to go below 140. Finally i began to panic and called my doctor, he told me to get used to it. He said I would be on metformin my whole life and eventually insulin. At that point i knew something wasn't right and began to do a lot of research. On August 13th I found Lisa's diabetes story (google " HOW EVER I FREED MYSELF FROM THE DIABETES " ) I read that article from end to end because everything the writer was saying made absolute sense. I started the diet that day and the next morning my blood sugar was down to 100 and now i have a fasting blood sugar between Mid 70's and the 80's. My doctor took me off the metformin after just three week of being on this lifestyle change. I have lost over 30 pounds and 6+ inches around my waist in a month

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Researchers implicate suspect in heart disease linked to diabetes - Medical Xpress

Cardiac Stem Cells Comments Off on Researchers implicate suspect in heart disease linked to diabetes – Medical Xpress | February 21st, 2017

Cells within our bodies divide and change over time, with thousands of chemical reactions occurring within each cell daily. This makes it difficult for scientists to understand whats happening inside. Now, tiny nanostraws developed by Stanford researchers offer a method of sampling cell contents without disrupting its natural processes.

Nicholas Melosh, associate professor of materials science and engineering, developed a new, non-destructive system for sampling cells with nanoscale straws. The system could help uncover mysteries about how cells function. (Image credit: L.A. Cicero)

A problem with the current method of cell sampling, called lysing, is that it ruptures the cell. Once the cell is destroyed, it cant be sampled from again. This new sampling system relies on tiny tubes 600 times smaller than a strand of hair that allow researchers to sample a single cell at a time. The nanostraws penetrate a cells outer membrane, without damaging it, and draw out proteins and genetic material from the cells salty interior.

Its like a blood draw for the cell, said Nicholas Melosh, an associate professor of materials science and engineering and senior author on a paper describing the work published recently in Proceedings of the National Academy of Sciences.

The nanostraw sampling technique, according to Melosh, will significantly impact our understanding of cell development and could lead to much safer and effective medical therapies because the technique allows for long term, non-destructive monitoring.

What we hope to do, using this technology, is to watch as these cells change over time and be able to infer how different environmental conditions and chemical cocktails influence their development to help optimize the therapy process, Melosh said.

If researchers can fully understand how a cell works, then they can develop treatments that will address those processes directly. For example, in the case of stem cells, researchers are uncovering ways of growing entire, patient-specific organs. The trick is, scientists dont really know how stem cells develop.

For stem cells, we know that they can turn into many other cell types, but we do not know the evolution how do they go from stem cells to, say, cardiac cells? There is always a mystery. This sampling technique will give us a clearer idea of how its done, said Yuhong Cao, a graduate student and first author on the paper.

The sampling technique could also inform cancer treatments and answer questions about why some cancer cells are resistant to chemotherapy while others are not.

With chemotherapy, there are always cells that are resistant, said Cao. If we can follow the intercellular mechanism of the surviving cells, we can know, genetically, its response to the drug.

The sampling platform on which the nanostraws are grown is tiny about the size of a gumball. Its called the Nanostraw Extraction (NEX) sampling system, and it was designed to mimic biology itself.

In our bodies, cells are connected by a system of gates through which they send each other nutrients and molecules, like rooms in a house connected by doorways. These intercellular gates, called gap junctions, are what inspired Melosh six years ago, when he was trying to determine a non-destructive way of delivering substances, like DNA or medicines, inside cells. The new NEX sampling system is the reverse, observing whats happening within rather than delivering something new.

Its a super exciting time for nanotechnology, Melosh said. Were really getting to a scale where what we can make controllably is the same size as biological systems.

Building the NEX sampling system took years to perfect. Not only did Melosh and his team need to ensure cell sampling with this method was possible, they needed to see that the samples were actually a reliable measure of the cell content, and that samples, when taken over time, remained consistent.

When the team compared their cell samples from the NEX with cell samples taken by breaking the cells open, they found that 90 percent of the samples were congruous. Meloshs team also found that when they sampled from a group of cells day after day, certain molecules that should be present at constant levels remained the same, indicating that their sampling accurately reflected the cells interior.

With help from collaborators Sergiu P. Pasca, assistant professor of psychiatry and behavioral sciences, and Joseph Wu, professor of radiology, Melosh and co-workers tested the NEX sampling method not only with generic cell lines, but also with human heart tissue and brain cells grown from stem cells. In each case, the nanostraw sampling reflected the same cellular contents as lysing the cells.

The goal of developing this technology, according to Melosh, was to make an impact in medical biology by providing a platform that any lab could build. Only a few labs across the globe, so far, are employing nanostraws in cellular research, but Melosh expects that number to grow dramatically.

We want as many people to use this technology as possible, he said. Were trying to help advance science and technology to benefit mankind.

Melosh is also a professor in the photon science directorate at SLAC National Accelerator Laboratory, a member of Stanford Bio-X, the Child Health Research Institute, the Stanford Neurosciences Institute, Stanford ChEM-H and the Precourt Institute for Energy. Wu is also the Simon H. Stertzer, MD, Professor; he is director of the Stanford Cardiovascular Institute and a member of Stanford Bio-X, the Child Health Research Institute, Stanford ChEM-H and the Stanford Cancer Institute. Pasca is also a member of Stanford Bio-X, the Child Health Research Institute, the Stanford Neurosciences Institute and Stanford ChEM-H.

The work was funded by the National Institute of Standards and Technology, the Knut and Alice Wallenberg Foundation, the National Institutes of Health, Stanford Bio-X, the Progenitor Cell Biology Consortium, the National Institute of Mental Health, an MQ Fellow award, the Donald E. and Delia B. Baxter Foundation and the Child Health Research Institute.

Link:
Stanford-developed nanostraws sample a cell's contents without damage - Stanford University News

Cardiac Stem Cells Comments Off on Stanford-developed nanostraws sample a cell’s contents without damage – Stanford University News | February 21st, 2017

SOUTH SAN FRANCISCO, CA--(Marketwired - February 13, 2017) - VistaGen Therapeutics Inc. (VTGN), a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders, today reported financial results for the third quarter of fiscal 2017 ended December 31, 2016.

The Company also provided a corporate update, including anticipated milestones for AV-101, its new generation, orally available CNS prodrug candidate in Phase 2 development, initially for the adjunctive treatment of major depressive disorder (MDD) in patients with an inadequate response to standard antidepressant therapies approved by the U.S. Food and Drug Administration (FDA).

"We are excited about our progress during the last quarter, with several key advances related to our MDD-focused programs for AV-101, as well as potential regenerative medicine and drug rescue applications of our cardiac stem cell technology. Following productive discussions with the FDA last quarter, our team and key advisors have been working diligently to complete the diverse regulatory and technical activities necessary to support the planned launch of our Phase 2b study of AV-101 next quarter, a study we believe has game-changing potential for the millions of patients who battle MDD every day with inadequate therapies," commented Shawn Singh, Chief Executive Officer of VistaGen. "Also, our recent sublicense agreement with BlueRock Therapeutics was an important advance in our cardiac stem cell program while we remain primarily focused on our Phase 2 programs for AV-101. With potentially catalytic milestones in the coming quarters, we believe we are poised to unlock significant value for our shareholders throughout 2017," added Mr. Singh.

Recent Corporate Highlights:

The U.S. National Institute of Mental Health (NIMH) is currently conducting and fully funding a 20 to 25-patient Phase 2a study of AV-101 as a monotherapy for treatment-resistant MDD under VistaGen's Cooperative Research and Development Agreement (CRADA) with the NIMH (Phase 2a Study). Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH and a leading clinical expert on the use of ketamine for treatment-resistant MDD, is the Principal Investigator of the Phase 2a Study. Following recent guidance from the NIMH, the Company currently anticipates that the NIMH will complete the Phase 2a Study by the end of 2017.

VistaGen is preparing to launch a 280-patient, multi-center, double-blind, placebo controlled Phase 2b efficacy and safety study evaluating AV-101 as a new generation adjunctive treatment for MDD patients with an inadequate response to standard, FDA-approved antidepressant therapies. The Company currently anticipates commencing patient enrollment in the Phase 2b Study in the second quarter of 2017. Dr. Maurizio Fava of Harvard University Medical School will serve as the Principal Investigator of VistaGen's AV-101 Phase 2b Study. Topline clinical results from the Phase 2b Study are currently anticipated by the end of 2018.

Dr. Mark Smith, Chief Medical Officer of VistaGen, commented, "We look forward to starting patient enrollment in our Phase 2b study of AV-101 as an adjunctive therapy in the treatment of MDD. We believe we have significantly de-risked this Phase 2b study with a clinical trial methodology that is designed to overcome the challenge of placebo effects in psychiatric clinical trials. Based on the study protocol we have designed in collaboration with key opinion leaders in depression and neuroscience, including our Principal Investigator, Dr. Fava, we expect that achieving a successful outcome of our Phase 2b study will be integral in realizing AV-101's potential to displace atypical antipsychotics and non-drug interventions in the current depression treatment paradigm, representing a much needed treatment solution for physicians and patients, as well as an enormous opportunity for VistaGen."

Expected Near-Term Milestones:

"The NIMH recently updated us on their timelines for the completion of the Phase 2a study of AV-101 as a monotherapy for MDD. The Phase 2a study protocol requires considerable time and dedication from both the study participants and the multi-disciplinary NIMH teams involved. Patient enrollment for the Phase 2a study remains ongoing and we currently anticipate the NIMH's completion of the study by the end of 2017. Our top priority is to execute our plans for our Phase 2b study of AV-101 as a new generation adjunctive treatment of MDD, and we remain on track to launch that important study in the second quarter. As part of our Phase 2 program, this Phase 2b study has been specifically designed to achieve important outcomes that will be key to advancing AV-101 into a pivotal program in MDD and more broadly beyond MDD, as we continue to advance our global commercialization strategy. We are confident that our Phase 2 program is a major step forward in positioning AV-101 as a potentially transformative adjunctive treatment of MDD and other CNS disorders," concluded Mr. Singh.

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Summary of Financial Results for the Third Quarter of Fiscal 2017 Ended December 31, 2016

Revenue

The Company recognized $1.25 million in sublicense revenue pursuant to its cardiac stem cell technology sublicense agreement with BlueRock Therapeutics, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, in the third fiscal quarter ended December 31, 2016.

Research and Development Expenses

Research and development expense totaled $1.61 million for the third fiscal quarter ended December 31, 2016, compared to $806,300 for the quarter ended December 31, 2015, reflecting increasing focus on nonclinical and clinical development of AV-101 and preparations for launch of the AV-101 Phase 2b Study in the second quarter of 2017.

General and Administrative Expenses

General and administrative expense increased to $2.3 million in the third fiscal quarter ended December 31, 2016, from $1.3 million for the same period in the prior year. The increase in G&A expense is the result of increased noncash stock compensation expense attributable to option and warrant grants in the period to employees, independent members of the Company's Board of Directors and consultants and other noncash expense related to grants of equity securities in payment of certain professional services, and a combination of corporate expenses, including investor relations and corporate development initiatives.

Net Loss

For the third fiscal quarter ended December 31, 2016, the Company reported a net loss of approximately $2.6 million, or a net loss attributable to common stockholders of $0.34 per common share, compared to a net loss of approximately $2.1 million, or a net loss attributable to common stockholders of $1.95 per common share for the same period in the prior year.

Cash and Cash Equivalents

As of December 31, 2016, the Company had approximately $5.6 million of cash, cash equivalents and short term receivables, including a $1.25 million short term sublicense fee receivable from BlueRock Therapeutics pursuant to the Company's December 2016 technology sublicense agreement with BlueRock Therapeutics. In January 2017, the Company received the $1.25 million sublicense fee payment from BlueRock Therapeutics and currently believes it has sufficient financial resources to fund its expected operations at least through the first half of 2017, including preparation for and launch of its planned AV-101 Phase 2b Study in MDD.

About VistaGen

VistaGen Therapeutics, Inc. (VTGN), is a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders. VistaGen's lead CNS product candidate, AV-101, is a new generation oral antidepressant drug candidate in Phase 2 development. AV-101's mechanism of action is fundamentally differentiated from all FDA-approved antidepressants and atypical antipsychotics used adjunctively to treat MDD, with potential to drive a paradigm shift towards a new generation of safer and faster-acting antidepressants. AV-101 is currently being evaluated by the U.S. National Institute of Mental Health (NIMH) in a Phase 2a monotherapy study in MDD being fully funded by the NIMH and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH. VistaGen is preparing to launch a 280-patient Phase 2b study of AV-101 as an adjunctive treatment for MDD patients with inadequate response to standard, FDA-approved antidepressant therapies. Dr. Maurizio Fava of Harvard University will be the Principal Investigator of the Phase 2b study. AV-101 may also have the potential to treat multiple CNS disorders and neurodegenerative diseases in addition to MDD, including chronic neuropathic pain, epilepsy, Parkinson's disease and Huntington's disease, where modulation of the NMDAR, AMPA pathway and/or key active metabolites of AV-101 may achieve therapeutic benefit.

VistaStem Therapeutics is VistaGen's wholly owned subsidiary focused on applying human pluripotent stem cell (hPSC) technology, internally and with third-party collaborators, to discover, rescue, develop and commercialize proprietary new chemical entities (NCEs), including small molecule NCEs with regenerative potential, for CNS and other diseases, and cellular therapies involving stem cell-derived blood, cartilage, heart and liver cells. In December 2016, VistaGen exclusively sublicensed to BlueRock Therapeutics LP, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, rights to certain proprietary technologies relating to the production of cardiac stem cells for the treatment of heart disease.

For more information, please visit http://www.vistagen.com and connect with VistaGen on Twitter, LinkedIn and Facebook.

Forward-Looking Statements

The statements in this press release that are not historical facts may constitute forward-looking statements that are based on current expectations and are subject to risks and uncertainties that could cause actual future results to differ materially from those expressed or implied by such statements. Those risks and uncertainties include, but are not limited to, risks related to the successful launch, continuation and results of the NIMH's Phase 2a (monotherapy) and/or the Company's planned Phase 2b (adjunctive therapy) clinical studies of AV-101 in MDD, and other CNS diseases and disorders, protection of its intellectual property, and the availability of substantial additional capital to support its operations, including the development activities described above. These and other risks and uncertainties are identified and described in more detail in VistaGen's filings with the Securities and Exchange Commission (SEC). These filings are available on the SEC's website at http://www.sec.gov. VistaGen undertakes no obligation to publicly update or revise any forward-looking statements.

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VistaGen Therapeutics Reports Fiscal Third Quarter 2017 Financial ... - Yahoo Finance

Cardiac Stem Cells Comments Off on VistaGen Therapeutics Reports Fiscal Third Quarter 2017 Financial … – Yahoo Finance | February 18th, 2017

OSAKA, Japan & LEUVEN, Belgium--(BUSINESS WIRE)--Takeda Pharmaceutical Company Limited (TSE:4502) (Takeda) and TiGenix NV (Euronext Brussels and Nasdaq:TIG) (TiGenix) today announced new data from the Phase 3 ADMIRE-CD clinical trial, which indicated that investigational compound Cx601, a suspension of allogeneic expanded adipose-derived stem cells (eASC), maintained long-term remission of treatment refractory complex perianal fistulas in patients with Crohns disease over 52 weeks.1 Results were presented at the 12th Congress of the European Crohns and Colitis Organisation (ECCO).

The ADMIRE-CD trial is a randomized, double-blind, controlled, Phase 3 trial, designed to investigate the efficacy and safety of the investigational compound Cx601 for the treatment of complex perianal fistulas in patients with Crohns disease.2 Patients were randomized to a single administration of Cx601 cells or placebo (control), both added to standard of care.1 A significantly greater proportion of patients in the Cx601 group versus the control group achieved clinical and radiological combined remission* (56.3% and 38.6%; p=0.010), and clinical remission (59.2% and 41.6%; p=0.013) at week 52 in the modified intention-to-treat population (mITT).1 Of those mITT patients who had shown combined remission at week 24, a greater number in the Cx601 group versus the control group reported no relapse at week 52 (75.0% and 55.9%).1 The rates and types of treatment related adverse events (non-serious and serious) and discontinuations due to adverse events were indicated to be similar in both groups (Cx601: 20.4%; control: 26.5%).1

Crohns disease is a chronic inflammatory disease of the gastrointestinal tract, which is thought to affect up to 1.6 million people in Europe.3 Complex perianal fistulas are a complication for people living with Crohns disease and there are limited treatment options. Recognizing the rare and debilitating nature of the disorder, and lack of treatment options, in 2009 the European Commission granted Cx601 orphan designation for the treatment of anal fistula. In March 2016, TiGenix announced that it submitted the Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for Cx601, and a decision by the EMA is expected in 2017. Additionally, in September 2016 orphan drug status was received from the Swiss Agency for Therapeutic Products (Swissmedic) regarding Cx601 for the rare disease complex perianal fistulas in Crohns disease.4

Perianal fistulizing Crohns disease is difficult to treat with currently available therapies and often leads to pain, swelling, infection and incontinence, said Dr. Asit Parikh, Head of Takedas Gastroenterology Therapeutic Area Unit. Existing therapies are limited and associated with complications and a high failure rate. Cx601 may offer patients an alternative treatment option.

These data highlight that the efficacy and safety of a single administration of Cx601 were maintained during one year of follow up, said Dr. Marie Paule Richard, Chief Medical Officer at TiGenix. It is important to also note that the definition of combined remission used in the ADMIRE-CD study, which includes both clinical and radiological assessment by MRI, is more stringent than the criteria commonly used in previous large scale, randomized clinical trials evaluating perianal fistulas in Crohns disease, based only on clinical assessment.

A global pivotal Phase 3 trial for U.S. registration with Cx601 for the treatment of complex perianal fistulas is expected to be initiated by TiGenix in 2017. In the U.S., TiGenix intends to apply for fast track designation from the U.S. Food and Drug Administration (FDA), which would facilitate and expedite the development and review process in the U.S.

Takedas Commitment to Gastroenterology

Takeda is a global leader in gastroenterology. With expertise spanning more than 25 years, the companys dedication to innovation continues to evolve and have a lasting impact. ENTYVIO (vedolizumab) demonstrates Takedas global capabilities and expansion into the specialty care market in gastroenterology and biologics. Designed and developed specifically to target the gastrointestinal (GI) tract, ENTYVIO was launched in 2014 for the treatment of adults with moderate to severe ulcerative colitis and Crohns disease. TAKECAB (vonoprazan fumarate) is Takeda's potassium-competitive acid blocker and was launched in Japan in 2015. Takeda also markets motility agent AMITIZA (lubiprostone), which originally launched in 2006 for the treatment of chronic idiopathic constipation, and received subsequent approval to treat irritable bowel syndrome with constipation and opioid-induced constipation. Preceding these notable launches, Takeda pioneered gastroenterological breakthroughs in proton pump inhibitors beginning in the 1990s with lansoprazole.Through specialized and strategic in-house development, external partnerships, in-licensing and acquisitions, Takeda currently has a number of promising early stage GI assets in development, and remains committed to delivering innovative, therapeutic options for patients with gastrointestinal and liver diseases.

About Takeda Pharmaceutical Company

Takeda Pharmaceutical Company Limited is a global, R&D-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its research efforts on oncology, gastroenterology and central nervous system therapeutic areas. It also has specific development programs in specialty cardiovascular diseases as well as late-stage candidates for vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as its presence in emerging markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.

About TiGenix

TiGenix NV (Euronext Brussels and Nasdaq: TIG) is an advanced biopharmaceutical company focused on developing and commercializing novel therapeutics from its proprietary platforms of allogeneic, or donor-derived, expanded stem cells. Our lead product candidate from the adipose-derived stem cell technology platform is Cx601, which is in registration with the EMA for the treatment of complex perianal fistulas in Crohns disease patients. Our adipose-derived stem cell product candidate Cx611 has completed a Phase I sepsis challenge trial and a Phase I/II trial in rheumatoid arthritis. Effective July 31, 2015, TiGenix acquired Coretherapix, whose lead cellular product candidate, AlloCSC-01, is currently in a Phase II clinical trial in acute myocardial infarction. In addition, the second product candidate from the cardiac stem cell-based platform acquired from Coretherapix, AlloCSC-02, is being developed in a chronic indication. On July 4, 2016, TiGenix entered into a licensing agreement with Takeda, a large pharmaceutical company active in gastroenterology, under which Takeda acquired the exclusive right to develop and commercialize Cx601 for complex perianal fistulas outside the United States. TiGenix is headquartered in Leuven (Belgium) and has operations in Madrid (Spain).

About Cx601

Cx601 is a suspension of allogeneic expanded adipose-derived stem cells (eASC) locally injected. Cx601 is an investigational compound being developed in Crohns disease for the treatment of complex perianal fistulas showing inadequate response to at least one conventional or biologic therapy including antibiotics, immunosuppressants, or anti-TNF agents. Crohns disease is a chronic inflammatory disease of the intestine and, as a complication of it, patients can suffer from complex perianal fistulas, for which there is currently no effective treatment. In 2009, the European Commission granted Cx601 orphan designation for the treatment of anal fistulas, recognizing the debilitating nature of the disease and the lack of treatment options. Cx601 has met the primary end-point in the Phase 3 ADMIRE-CD study, a randomized, double-blind, controlled trial run in Europe and Israel and designed to comply with the requirements laid down by the EMA. Madrid Network issued a soft loan to help finance this Phase 3 study, which was funded by the Secretary of State for Research, Development and Innovation (Ministry of Economy and Competitiveness) within the framework of the INNTEGRA plan. In this trial, patients were randomized to a single administration of Cx601 cells or placebo (control), both added to standard of care. The studys primary endpoint was combined remission, defined as clinical assessment at week 24 of closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections >2cm confirmed by MRI. In the ITT population (n=212), Cx601 achieved statistically significant superiority (p=0.024) on the primary endpoint with 50% combined remission at week 24 compared to 34% in the control arm. Efficacy results were robust and consistent across all statistical populations. Treatment emergent adverse events (non-serious and serious) and discontinuations due to adverse events were comparable between Cx601 and control arms. The 24-week results have been published by The Lancet, one of the most highly regarded and well known medical journals in the world. The Phase 3 study has completed a follow-up analysis at 52 weeks confirming its sustained efficacy and safety profile. Top line follow-up data showed that in the ITT population Cx601 achieved statistical superiority (p=0.012) with 54% combined remission at week 52 compared to 37% in the control arm. Long-term results also showed that, of patients with combined remission at week 24, a higher proportion of patients treated with Cx601 had no relapse at week 52 (75.0% vs. 55.9%). Based on the positive 24-weeks Phase 3 study results, TiGenix has submitted a Marketing Authorization Application to the EMA in early 2016. TiGenix is preparing to develop Cx601 in the U.S. after having reached an agreement with the FDA through a special protocol assessment procedure (SPA) in 2015. On July 4, 2016, TiGenix entered into a licensing agreement with Takeda, a pharmaceutical company leader in gastroenterology, whereby Takeda acquired an exclusive right to develop and commercialize Cx601 for complex perianal fistulas in Crohns patients outside of the U.S.

-Ends-

____________

* defined as clinical assessment of closure of all treated external openings draining at baseline, despite gentle finger compression, and absence of collections >2cm confirmed by MRI

References

1 Pans, J, Garca-Olmo, D, Van Assche, G, et al., Long-term efficacy and safety of Cx601, allogeneic expanded adipose-derived mesenchymal stem cells, for complex perianal fistulas in Crohns Disease: 52-week results of a phase III randomized controlled trial. ECCO 2017; Barcelona: Abstract OP009.

2 Clinicaltrials.gov. Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn's Disease (ADMIRE-CD). https://clinicaltrials.gov/ct2/show/NCT01541579?term=cx601&rank=2. Published February 2012. Accessed February 9, 2017.

3 Burisch, J, Jess, T, Martinato, M, et al., on behalf of ECCO EpiCom. The burden of inflammatory bowel disease in Europe. J Crohns Colitis. 2013; 7: 322-337.

4 Swissmedic. About us Collaboration National collaboration Patients and Users. Available at https://www.swissmedic.ch/ueber/01398/01400/03296/index.html?lang=en. Accessed February 9, 2017.

Original post:
Takeda and TiGenix Report New Data Highlighting Maintenance of ... - Business Wire (press release)

Cardiac Stem Cells Comments Off on Takeda and TiGenix Report New Data Highlighting Maintenance of … – Business Wire (press release) | February 17th, 2017

February 15, 2017 A single human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM). Cells such as these were used to assess tyrosine kinase inhibitors for cardiotoxicity in a high-throughput fashion. Credit: Dr. Arun Sharma at Dr. Joseph Wus laboratory at Stanford University

Researchers at the Stanford University School of Medicine used heart muscle cells made from stem cells to rank commonly used chemotherapy drugs based on their likelihood of causing lasting heart damage in patients.

Drugs known as tyrosine kinase inhibitors can be an effective treatment for many types of cancers, but they also have severe and sometimes fatal side effects. Using lab-grown heart cells, Stanford researchers were able to assess the drugs' various effects on heart muscle cells, including whether the cells survived, were able to beat rhythmically and effectively, responded appropriately to electrophysiological signals and communicated with one another.

The researchers found that their assay can accurately identify those tyrosine kinase inhibitors already known to be the most dangerous in patients. In the future, they believe their system may prove useful in the early stages of drug development to screen new compounds for cardiotoxicity.

"This type of study represents a critical step forward from the usual process running from initial drug discovery and clinical trials in human patients," said Joseph Wu, MD, PhD, director of the Stanford Cardiovascular Institute and a professor of cardiovascular medicine and of radiology. "It will help pharmaceutical companies better focus their efforts on developing safer drugs, and it will provide patients more effective drugs with fewer side effects."

A paper describing the research will be published Feb. 15 in Science Translational Medicine. Wu, who holds the Simon H. Stertzer Professorship, is the senior author. Former graduate student Arun Sharma, PhD, is the lead author.

'Multiple measurements'

"We used multiple measurements to accurately predict which of the tyrosine kinase inhibitors were the most cardiotoxic," said Sharma. "The drugs with the lowest safety indices in our study were also those identified by the Food and Drug Administration as the most cardiotoxic to patients. Other drugs that are not as cardiotoxic performed much better in our assays."

Validating the researchers' cardiac-safety test on drugs with extensive clinical track records is necessary before the assay can be used to predict with confidence the likely clinical outcomes of drugs still under development.

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Sharma, Wu and their colleagues created heart muscle cells called cardiomyocytes from induced pluripotent stem cells, or iPS cells, from 11 healthy people and two people with kidney cancer. They grew the lab-made cardiomyocytes in a dish and tested the effects of 21 commonly used tyrosine kinase inhibitors on the cells.

They found that treatment with drug levels equivalent to those taken by patients often caused the cells to beat irregularly and begin to die. The cells also displayed differences in the electrophysiological signaling that controls their contraction. The researchers used these and other measurements to develop a cardiac safety index for each drug.

They found that those drugs known to be particularly dangerous to heart function, such as nilotinib, which is approved for the treatment of chronic myelogenous leukemia, and vandetanib, which is approved for the treatment of some types of thyroid cancer, also had the lowest safety indices based on the assay; conversely, those known to be better tolerated by patients ranked higher on their safety index. Prescribing information for both nilotinib and vandetanib contains warnings from the FDA about the drugs' potential cardiotoxicity.

An activity increase in an insulin responsive pathway

Six of the 21 tyrosine kinase inhibitors tested were assigned cardiac safety indices at or below 0.1the threshold limit at which the researchers designated a drug highly cardiotoxic. Three of these six are known to inhibit the same two signaling pathways: VEGFR2 and PDGFR. The researchers noticed that cells treated with these three drugs ramped up the activity of a cellular signaling pathway that responds to insulin or IGF1, an insulinlike growth factor.

This discovery, coupled with the fact that treatment with insulin or IGF1 is known to enhance heart function during adverse cardiac events such as heart attacks, led the researchers to experiment further. They found that exposing the cells to insulin or IGF1 made it less likely they would die due to tyrosine kinase inhibitors blocking the VEGFR2 and PDGFR pathways. Although more research is needed, these findings suggest it may be possible to alleviate some of the heart damage in patients receiving these chemotherapies.

The current study mirrors another by Wu's lab that was published in April 2016 in Nature Medicine. That research focused on the toxic effect of a chemotherapy drug called doxorubicin on iPS cell-derived cardiomyocytes. Doxorubicin, which indiscriminately kills any replicating cells, is increasingly being replaced by more targeted, cancer-specific therapies such as the tyrosine kinase inhibitors tested in the current study.

"The switch from doxorubicin is a result of the paradigm shift in cancer treatment to personalized, precise treatment as emphasized by President Obama's 2015 Precision Medicine Initiative," said Wu. "Moving even further, we're discovering that many tyrosine kinase inhibitors are themselves significantly cardiotoxic, and some have been withdrawn from the market. There is a critical need for a way to 'safety test' all drugs earlier in development before they are administered to patients. Our drug safety index is a step in that direction."

Explore further: Stem cell-based screening methods may predict heart-related side effects of drugs

More information: "High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells," Science Translational Medicine, stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaf2584

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Fat cells are not simply big blobs of lipid quietly standingby in the bodyinstead, they send out hormones and other signaling proteins that affect many types of tissues. Scientists at Joslin Diabetes Center now have identified ...

Researchers at the Stanford University School of Medicine used heart muscle cells made from stem cells to rank commonly used chemotherapy drugs based on their likelihood of causing lasting heart damage in patients.

Research published today in Nature from scientists at Huntsman Cancer Institute (HCI) at the University of Utah shows how epithelial cells naturally turn over, maintaining constant numbers between cell division and cell death.

Scientists are working to understand the mechanisms that make weight loss so complicated. Exercise burns calories, of course, but scientists are also looking at how the body burns more energy to stay warm in cold temperatures.

Biologists have known for decades that enduring a short period of mild stress makes simple organisms and human cells better able to survive additional stress later in life. Now, scientists at Sanford Burnham Prebys Medical ...

A puzzling question has lurked behind SMA (spinal muscular atrophy), the leading genetic cause of death in infants.

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Scientists create scorecard index for heart-damaging chemo drugs - Medical Xpress

Cardiac Stem Cells Comments Off on Scientists create scorecard index for heart-damaging chemo drugs – Medical Xpress | February 15th, 2017

Seventy-year-old Peggy Agar has known since she was in her 40s that she and her 12 siblings might be at risk for familial cardiomyopathy, a genetic form of heart disease.

Her mother was diagnosed with it in 1987, and several of her brothers were also subsequently diagnosed with cardiomyopathy.

Given our family history, our family knew we had to be vigilant to keep our hearts as strong as possible, says Agar, who lives in Bloomfield.

But now thanks to the power of genetic testing at UConn Healths Pat and Jim Calhoun Cardiology Center, Agar and her family can determine which family members may be at risk.

Through a routine blood sample, Agars gene sequences were analyzed by Dr. Travis Hinson, a cardiovascular physician-scientist who is a new faculty member with a joint appointment at UConn Health and the Jackson Laboratory for Genomic Medicine.

Hinsons advanced genetic analysis revealed that Agar carries a gene mutation that causes dilated cardiomyopathy, a disease of the heart muscle that potentially leads to an enlarged, weakened heart and ultimately heart failure. He identified that Agar carries a mutation in the largest gene in the body called titin that leads to dilated cardiomyopathy in about 1 in 5 patients with a positive family history. In 2015, his laboratory published these findings in the journal Science, where he studied miniature beating human heart tissues engineered from stem cells from patients with conditions similar to Agars.

Hinson says knowing their genetic predisposition allows patients and families to understand why heart disease may continue to be prevalent generation after generation in their family.

If you carry the cardiomyopathy gene, you have a 50 percent chance of passing it to your offspring, says Hinson. Now with the power of genetic testing, we can tell each family member definitely early in their life whether they carry the cardiomyopathy genetic mutation, and intervene early to try to prevent any symptoms of the disease before they occur.

Agar says the genetic test results will arm her familys younger and future generations with important knowledge.

Now our family can better safeguard ourselves and younger generations at an early age to take extra precautions when it comes to our heart health, she says. Because of the way this myopathy develops in our family, we have learned that it is very important when we seek medical care that the physicians we see are aware of this family history.

Another positive aspect of the testing is that family members who are found not to have the gene no longer need to worry about passing the gene on to their children.

Agar has received comprehensive treatment from a team of physicians at UConn Healths Calhoun Cardiology Center, including cardiologist Dr. Jason Ryan and electrophysiologist Dr. Christopher Pickett. Since she was first diagnosed with cardiomyopathy in 2009, she has been treated for its complications. These include atrial fibrillation, the most common form of arrhythmia, and ventricular tachycardia, life-threatening and chaotic heart beats that can cause premature or sudden death. To protect her heart against dangerous arrhythmias, Agar takes daily medication; has received cardioversions (which convert an arrhythmia to a normal rhythm) and an ablation procedure (the destruction of tinyparts of heart tissue with radio frequency waves that are triggering arrhythmia); and has an implantable cardio-defibrillator.

As a result of the personalized team approach among the cardiologists who care for her at the Calhoun Cardiology Center, Agars heart function has been nearly normalized. She is grateful to the entire team.

Ive been fortunate, she says. UConns cardiac health team and their staff have been very supportive. They are truly experts in their field and treat me in a very professional and personal manner. They welcome questions and listen to my concerns. They convey the feeling that they truly care about my well-being.

Cardiomyopathy is the most common cause of heart failure. While it can be a genetic condition, it can also be caused by a heart attack or unhealthy lifestyle.

Agar advises others who may have a recurring theme of heart trouble in their family to seek care and not ignore it. With appropriate treatment, she says, cardiac problems dont necessarily have to significantly impact your quality of life. Remember that you are in charge of your own health. Pay attention to the advice of your health care professionals and do those things that are necessary for good health.

To learn more about the Calhoun Cardiology Center at UConn Health, visit: health.uconn.edu/cardiology.

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Cardiovascular Genetic Testing Empowers Patient, Family - UConn Today

Cardiac Stem Cells Comments Off on Cardiovascular Genetic Testing Empowers Patient, Family – UConn Today | February 15th, 2017

Scientists are one step closer to mimicking the way biological systems interact and process information in the body -- a vital step toward developing new forms of biorobotics and novel treatment approaches for several muscle-related health problems such as muscular degenerative disorders, arrhythmia and limb loss.

Using cardiac muscle cells and cardiac fibroblasts -- cells found in connective heart tissue -- researchers at the University of Notre Dame have created a "living diode," which can be used for cell-based information processing, according to a recent study in Advanced Biosystems. Bioengineers created the muscle-based circuitry through a novel, self-forming, micro patterning approach.

Using muscle cells opens the door to functional, biological structures or "computational tissues" that would allow an organ to control and direct mechanical devices in the body. The design arranges the two types of cells in a rectangular pattern, separating excitable cells from nonexcitable cells, allowing the team to transduce electrical signals unidirectionally and achieve a diode function using living cells. In addition to the diode-like function, the natural pacing ability of the muscle cells allowed Pinar Zorlutuna, assistant professor of aerospace and mechanical engineering, and her team to pass along information embedded in the electrical signals by modulating the frequency of the cells' electrical activity. Zorlutuna's research was funded by the National Science Foundation.

"Muscle cells have the unique ability to respond to external signals while being connected to fibroblasts internally through intercellular junctions. By combining these two cell types, we have the ability to initiate, amplify and propagate signals directionally," said Zorlutuna, who is also director of the Tissue Engineering Laboratory at the university. "The success of these muscle-cell diodes offers a path toward linking such cell-based circuitry to a living system -- and creating functional control units for biomedical engineering applications such as bioactuators or biosensors."

The team's work presents a new option in biocomputing, which has focused primarily on using gene circuitries of genetically modified single-cells or neuronal networks doped with chemical additives to create information processing systems. The single-cell options are slower to process information since they relay on chemical processes, and neuronal-based approaches can misfire signals, firing backward up to 10 percent of the time.

Zorlutuna explores biomimetic environments in order to understand and control cell behavior. She also studies cell-cell and cell-environment interactions through tissue and genetic engineering, and micro- and nanotechnology at the Notre Dame Center for Nano Science and Technology. She is a researcher at the University's Center for Stem Cells and Regenerative Medicine and the Harper Cancer Research Institute.

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Researchers develop 'living diode' using cardiac muscle cells - Science Daily

Cardiac Stem Cells Comments Off on Researchers develop ‘living diode’ using cardiac muscle cells – Science Daily | February 15th, 2017

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Myocardial Stem Cell Patch Developed with 3D Printer BusinessKorea The myocardial patch, which is printed with a 3D printer and attached to the hearts of such patients for blood vessel and tissue regeneration, has a structure in which cardiac extracellular matrices are used as bio ink and cardiac stem cells and ...

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Myocardial Stem Cell Patch Developed with 3D Printer - BusinessKorea

Cardiac Stem Cells Comments Off on Myocardial Stem Cell Patch Developed with 3D Printer – BusinessKorea | February 11th, 2017

When Becky's baby girl started sweating, vomiting and struggling to breathe while breastfeeding , she knew something was wrong.

But despite taking her daughter, Kirsty, to the GP numerous times, she was dismissed as "neurotic" and "unable to cope", a new book reveals.

Even when the six-month-old was finally referred to hospital for X-Rays, paediatricians wrongly diagnosed her condition as bronchitis.

It was only when she was close to death, lying limp and grey in her terrified mum's arms, that the true cause of her illness was diagnosed.

She had severe heart failure after "multiple heart attacks" - which she had suffered from 'silently', unable to communicate or understand them.

Kirsty wasnt gaining weight," writes world-famous cardiac surgeon Stephen Westaby in his remarkable book, Fragile Lives , published today.

"She had a pasty, washed-out look and a cough like a dogs bark.

In reality, this baby was suffering repeated small heart attacks with excruciating chest pain that she could neither communicate nor understand.

"The human body can be outlandishly cruel.

Stephen, from Oxford, operated on Kirsty following her ALCAPA (anomalous left coronary artery from the pulmonary artery) diagnosis.

He found the situation "even worse" than he had thought and, at one point, Becky and her husband were warned they would likely lose their baby.

However, in a desperate, last-ditch attempt to save the youngster's life, Stephen carried out a procedure that had never been done before in a child.

He made her heart smaller by removing almost a third of it, before stitching the organ back up until it looked like a "quivering black banana".

Amazingly, he saved his tiny patient's life.

Today, Kirsty is an 18-year-old, athletic student. She has been able to attend school, go to prom and spend time with her friends.

Her incredible story is one of many featured in Stephen's new book, which details some of the surgeon's most extraordinary and poignant cases.

Others include a woman who lived the horror of locked-in syndrome, and a man whose life was powered by a battery for more than seven years

They all include drama, emotion and blood (lots of it).

Having grown up on a council estate in Scunthorpe, North Lincolnshire, Stephen went into cardiac surgery after watching his granddad die of heart failure.

He tells Mirror Online that, despite his passion for the speciality and his determination, he "never anticipated" he would even get to medical school.

But over the past nearly 40 years, he has become an acclaimed heart surgeon and pioneer, responsible for a number of significant developments in the field.

He invented a T-Y stent - dubbed the "Westaby" tube - to bypass damaged airways, and became the first surgeon to fit a patient with a new type of artificial heart.

The patient, Peter, died aged 69 after over seven years of "extra life". "He was the first to reveal the true potential of blood pump technology," writes Stephen in his book.

The surgeon, who has worked in hospitals in the UK and abroad, says he learned "very early on" that a lot of patients were being turned away for heart transplants.

"Although transplants were great for patients, a lot of others were being turned away," he says. "Very few people can have heart transplants.

"They need someone else to die to get their heart.

He says that, even as a trainee, he was interested in alternative options for the unfortunate patients who could not receive a transplant.

In his book, he describes how, as a student, he was called to assist an operation on a young car crash victim after drinking pints in the pub.

"Bad problem, both the injury and the beer," he writes in his book.

"Not so much the amount of alcohol - we were used to that - more the volume of urine to pass during a four-hour operation."

To get through the surgery without losing concentration or having to leave, he reveals how he used rubber tubing so his urine would run into his surgical boots.

He admits, at one point, he had to cough loudly to disguise the "squelching sound".

When you start doing any surgery, it is scary. It takes you a few months to get into," says the dad-of-two. "Its very taxing."

In subsequent decades, Stephen went on to save hundreds of lives, repeatedly taking chances and pushing the boundaries of heart surgery.

This was all part of being a pioneer, pushing the profession to its limit," he says.

Far from working nine-to-five, the surgeon spent his mornings, afternoons and evenings dedicated to his "day job".

To become a heart surgeon I believe you have to work continuously in the way I did in the old days," he tells Mirror Online.

"We had ward rounds at 5am, then wed operate at 7am.

Stephen would spend the rest of the day operating on patients, before going to the research lab. In the evenings, he'd return to intensive care.

"It needs that sort of dedication," he says.

Indeed, it was this dedication that saw him cut a conference in Australia short to rush back to perform life-saving surgery on Kirsty.

Stephen had been in the country for just 13 hours when he received a call from Nick Archer, his paediatric cardiology colleague at Oxfords John Radcliffe Hospital.

No one calls with good news at night, he notes in his book.

And he was right.

He was told that there was a sick baby with ALCAPA - a rare but serious cardiac anomaly - who desperately needed his help.

He later discovered that Kirsty - in whom fate had installed a lethal self-destruct mechanism" - had shown signs of distress within days of her birth.

Her mum Becky, who already had a three-year-old son, noticed beads of sweat were trickling from her baby's nose whenever she tried to breastfeed her.

However, a paediatrician dismissed the infant's symptoms, Stephen writes in his book, deeming the move an example of "p***-poor medicine".

Within a matter of weeks, Kirsty was sweating, vomiting and struggling to breathe during feeds. However, she had no temperature.

Her concerned mum repeatedly took her to visit the doctor, but was "deemed neurotic and unable to cope", according to Fragile Lives.

At the time, Becky's husband was working abroad, away from their daughter who had a "pasty look" and a "cough like a dog's bark".

After eventually managing to get Kirsty referred to a hospital for X-Rays, Becky was told that her baby was suffering from bronchitis.

Feeling desperate and certain that something "dreadful" was going to happen, she later took the "grey" youngster to another hospital.

But there, she was diagnosed with the same condition.

Now late at night, Becky demanded a further X-Ray. Shockingly, she was "told off for her unreasonable attitude," Stephen writes in his moving book.

However, after the scan, the mum finally had her fears confirmed.

Her daughter was found to have a massive heart, with medics having reportedly misinterpreted heart shadows on her X-Rays as fluid.

Kirsty was rushed to Oxford's specialist childrens heart unit. By then, she was very cold and suffering from severe heart failure, Stephen says.

While flying back from Australia, the surgeon devised an alternative technique for the operation in a bid to increase the baby's chance of survival.

After landing in the UK, however, he was shocked by Kirsty's condition.

"She was emaciated, with virtually no body fat, her heaving ribs and rapid breathing a consequence of her congested lungs, and her abdomen swollen with fluid," he writes.

He adds: Without immediate surgery, shed be dead within days.

Joined by his surgical team, Stephen opened up the baby's small body with a scalpel blade, an electrical saw and a rib retractor while her parents faced an anxious wait.

He describes in his book how he found her heart to be the size of a lemon.

Babies' hearts are typically the size of a walnut.

Stephen then goes on to explain how he replumbed Kirsty's heart's blood supply and removed up to 30 per cent of her organ in an attempt to save her.

Incredibly, the surgery was a success.

The operation "provided some of the first evidence that an infants own cardiac stem cells can regenerate heart muscle and actually remove fibrous tissue," Stephen says.

"Adult hearts cannot recover in the same way," he writes.

Speaking to the Mirror Online, the surgeon describes how he "always put the patient first", even if it meant the possibility of being sacked.

He admits he did things "off piste" and, when he didn't have the money to perform certain procedures, he would raise charitable funds.

I used to operate on everyone from premature babies in their cots to people all the way through to their nineties," he says.

"Every one is precious."

He adds that it takes a "special sort of person" - one who is extremely skilled, gutsy and empathetic - to operate on babies and children.

"I think you find it difficult every time you lose a patient, no matter how high risk they are," he says.

"I used to really hate having to go out of an operating theatre and telling [relatives] their loved one had died.

Stephen, who describes his own story as one of "grim determination", worked on around 12,000 patients during his career.

He estimates between 300 and 400 died earlier than they would have.

I did lose an awful lot of patients," he says.

"There are lots of cases that have stuck with me.

But he adds: "Very few heart patients die because the surgeon doesnt do a good job.

He says some patients suffer complications which aren't managed well, while the quality of the intensive care team can also have an impact.

Nowadays, surgeons' death rates are published. There is also a risk of legal action by grief-stricken and angry relatives, Stephen says.

This 'naming and shaming' culture, he claims, is having a negative effect on the profession and putting graduates off from going into heart surgery.

"It's a worrying time for trainees," he says, describing how there are "serious weaknesses" with the system. "Surgeons now have their death rates published."

He adds that this also means it's difficult to maintain consistent intensive care teams.

"There's a lot of agency nurses, people not familiar with protocol," he says.

Stephen, who established the Oxford Heart Centre in the 1980s, recently retired from surgery after developing Dupuytren's contracture, or a 'claw hand'.

"My hand was warped into the position in which I held the scissors, the needle holder, the sternal saw," the 68-year-old writes in his book.

Now, he is working in two "very exciting" roles, one of which involves a proposed Wellness and Life Science Village in Llanelli, Wales.

He is also medical director at the regenerative medicine firm, Celixir , which he says has made "very important" developments for people with heart failure.

Reflecting on his incredible career, Stephen, who lives with his wife, Sarah, 63, acknowledges that he "didn't give enough time" to his family.

He met his spouse - a "free spirit from Africa" - over an open chest in Accident & Emergency, where she was working as a sister.

Stephen has a 38-year-old daughter - by his first wife, Jane - and a 28-year-old son - by Sarah, as well as two young granddaughters.

I never gave enough time to my kids and my grandchildren," he admits.

But he adds that one of the reasons he wrote his book, "was so they could see why I wasnt with them as much as I could be".

Stephen appeared on ITV's This Morning today, along with Kirsty and Becky.

Viewers have since taken to social media to praise his "amazing" and "remarkable" work, with some calling for him to be knighted.

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Mum dismissed as 'neurotic and unable to cope' after baby girl ... - Mirror.co.uk

Cardiac Stem Cells Comments Off on Mum dismissed as ‘neurotic and unable to cope’ after baby girl … – Mirror.co.uk | February 9th, 2017

A new revolutionary stem cell technique is being used to treat those suffering from damaged muscles without the cancer risk that was previously present. This was the first time that researchers had successfully implanted synthetic stem cardiac cells that managed to repair the muscle that a previous heart attack has weakened. Cancer was previously a risk with traditional stem cell therapy as scientists were unable to stop formertumors as the cells continued to replicate.

This procedure is mostly performed on those suffering from blood or bone marrow cancers such as leukemia. But, researchers are also working on developing effective stem cell treatments for those diagnosed with neurodegenerative diseases such as Parkinsons and heart disease too.

Synthetic stem cells are very handy because unlike natural stem cells, theyre easy to preserve and can be adapted to be used in various parts of the body. Ke Cheng, associate professor of molecular biomedical sciences at North Carolina State University, said, We are hoping that this may be the first step towards a truly off-the-shelf cell product that would enable people to receive beneficial stem cell therapies when theyre needed, without costly delays.

[The study can be found here.]

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:Pioneering Stem Cell Technique Promise Muscle Regeneration Without Cancer Risk

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Regrowing heart muscles without cancer risk, using synthetic stem cells - Genetic Literacy Project

Cardiac Stem Cells Comments Off on Regrowing heart muscles without cancer risk, using synthetic stem cells – Genetic Literacy Project | February 7th, 2017

Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem celllike state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. Although these cells meet the defining criteria for pluripotent stem cells, it is not known if iPSCs and embryonic stem cells differ in clinically significant ways. Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007. Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cells from all three germ layers, and being able to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers.

Although additional research is needed, iPSCs are already useful tools for drug development and modeling of diseases, and scientists hope to use them in transplantation medicine. Viruses are currently used to introduce the reprogramming factors into adult cells, and this process must be carefully controlled and tested before the technique can lead to useful treatment for humans. In animal studies, the virus used to introduce the stem cell factors sometimes causes cancers. Researchers are currently investigating non-viral delivery strategies. In any case, this breakthrough discovery has created a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined. In addition, tissues derived from iPSCs will be a nearly identical match to the cell donor and thus probably avoid rejection by the immune system. The iPSC strategy creates pluripotent stem cells that, together with studies of other types of pluripotent stem cells, will help researchers learn how to reprogram cells to repair damaged tissues in the human body.

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Stem Cell Basics VI. | stemcells.nih.gov

Cardiac Stem Cells Comments Off on Stem Cell Basics VI. | stemcells.nih.gov | February 3rd, 2017

Cardiac muscle cells or cardiomyocytes (also known as myocardiocytes[1] or cardiac myocytes[2]) are the muscle cells (myocytes) that make up the cardiac muscle. Each myocardial cell contains myofibrils, which are specialized organelles consisting of long chains of sarcomeres, the fundamental contractile units of muscle cells. Cardiomyocytes show striations similar to those on skeletal muscle cells. Unlike multinucleated skeletal cells, the majority of cardiomyocytes contain only one nucleus, although they may have as many as four.[3] Cardiomyocytes have a high mitochondrial density, which allows them to produce adenosine triphosphate (ATP) quickly, making them highly resistant to fatigue.

There are two types of cells within the heart: the cardiomyocytes and the cardiac pacemaker cells. Cardiomyocytes make up the atria (the chambers in which blood enters the heart) and the ventricles (the chambers where blood is collected and pumped out of the heart). These cells must be able to shorten and lengthen their fibers and the fibers must be flexible enough to stretch. These functions are critical to the proper form during the beating of the heart.[4]

Cardiac pacemaker cells carry the impulses that are responsible for the beating of the heart. They are distributed throughout the heart and are responsible for several functions. First, they are responsible for being able to spontaneously generate and send out electrical impulses. They also must be able to receive and respond to electrical impulses from the brain. Lastly, they must be able to transfer electrical impulses from cell to cell.[5]

All of these cells are connected by cellular bridges. Porous junctions called intercalated discs form junctions between the cells. They permit sodium, potassium and calcium to easily diffuse from cell to cell. This makes it easier for depolarization and repolarization in the myocardium. Because of these junctions and bridges the heart muscle is able to act as a single coordinated unit.[6][7]

The cardiomyocytes are about 100 to 150 micrometers long and 15 to 20 micrometers in diameter.[citation needed]

Humans are born with a set number of heart muscle cells, or cardiomyocytes, which increase in size as heart grows larger during childhood development. Recent evidence suggests that cardiomyocytes are actually slowly turned over as we age, but that less than 50% of the cardiomyocytes we are born with are replaced during a normal life span.[8] The growth of individual cardiomyocytes not only occurs during normal heart development, it also occurs in response to extensive exercise (athletic heart syndrome), heart disease, or heart muscle injury such as after a myocardial infarction. A healthy adult cardiomyocyte has a cylindrical shape that is approximately 100m long and 10-25m in diameter. Cardiomyocyte hypertrophy occurs through sarcomerogenesis, the creation of new sarcomere units in the cell. During heart volume overload, cardiomyocytes grow through eccentric hypertrophy.[9] The cardiomyocytes extend lengthwise but have the same diameter, resulting in ventricular dilation. During heart pressure overload, cardiomyocytes grow through concentric hypertrophy.[9] The cardiomyocytes grow larger in diameter but have the same length, resulting in heart wall thickening.

Cardiac action potential consists of two cycles, a rest phase and an active phase. These two phases are commonly understood as systole and diastole. The rest phase is considered polarized. The resting potential during this phase of the beat separates the ions such as sodium, potassium and calcium. Myocardial cells possess the property of automaticity or spontaneous depolarization. This is the direct result of a membrane which allows sodium ions to slowly enter the cell until the threshold is reached for depolarization. Calcium ions follow and extend the depolarization even further. Once calcium stops moving inward, potassium ions move out slowly to produce repolarization. The very slow repolarization of the CMC membrane is responsible for the long refractory period.[10][11]

Myocardial infarction, commonly known as a heart attack, occurs when the heart's supplementary blood vessels are obstructed by an unstable build-up of white blood cells, cholesterol, and fat. With no blood flow, the cells die, causing whole portions of cardiac tissue to die. Once these tissues are lost, they cannot be replaced, thus causing permanent damage. Current research indicates, however, that it may be possible to repair damaged cardiac tissue with stem cells,[12] as human embryonic stem cells can differentiate into cardiomyocytes under appropriate conditions.[13]

The cardiomyopathies are a group of diseases characterized by disruptions to cardiac muscle cell growth and / or organization. Presentation can range from asymptomatic to sudden cardiac death.

Cardiomyopathy can be caused by genetic, endocrine, environmental, or other factors.

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Cardiac muscle cell - Wikipedia

Cardiac Stem Cells Comments Off on Cardiac muscle cell – Wikipedia | February 3rd, 2017