Abstract

Cardiovascular disease is a major cause of morbidity and mortality throughout the world. Most cardiovascular diseases, such as ischemic heart disease and cardiomyopathy, are associated with loss of functional cardiomyocytes. Unfortunately, the heart has a limited regenerative capacity and is not able to replace these cardiomyocytes once lost. In recent years, stem cells have been put forward as a potential source for cardiac regeneration. Pre-clinical studies that use stem cell-derived cardiac cells show promising results. The mechanisms, though, are not well understood, results have been variable, sometimes transient in the long term, and often without a mechanistic explanation. There are still several major hurdles to be taken. Stem cell-derived cardiac cells should resemble original cardiac cell types and be able to integrate in the damaged heart. Integration requires administration of stem cell-derived cardiac cells at the right time using the right mode of delivery. Once delivered, transplanted cells need vascularization, electrophysiological coupling with the injured heart, and prevention of immunological rejection. Finally, stem cell therapy needs to be safe, reproducible, and affordable. In this review, we will give an introduction to the principles of stem cell based cardiac repair.

Keywords: Stem cell, Regeneration, Heart, Cardiomyocytes

Repairing the injured body with its own tissue as a substrate has captured human fascination for a long time. In Greek mythology, the Lernaean Hydra was a serpent-like creature with multiple heads that regenerated each time they were cut off and Prometheus, a titan punished by Zeus for stealing fire, had a liver that was able to regenerate each night after it was eaten by an eagle. In 1740, Abraham Tembley discovered that microscopic, freshwater animals had the ability to regenerate their head after amputation, later followed by others who discovered that amphibians have the ability to regenerate their tails, limbs, jaws, and eyes.[1],[2] It took scientists until 1933 before they discovered that some human organs, such as the liver, also have the ability to regenerate.[3]

Regenerative therapies are of major interest in cardiovascular medicine. Most cardiovascular diseases, including ischemic heart disease and cardiomyopathy, are associated with loss of functional cardiomyocytes and in other diseases, such as sick sinus syndrome, specific cardiac cell properties are missing. Unlike the Lernaean Hydra or the human liver, the heart does not have the ability to regenerate itself spontaneously once damaged. Cardiomyocytes are terminally differentiated and have a limited proliferative capacity. Lost cardiomyocytes are replaced by fibroblasts and connective tissue with the remaining cardiomyocytes becoming hypertrophic, which may eventually lead to heart failure. On the contrary, stem cells proliferate indefinitely and can be directed to differentiate into specialized cell types such as cardiomyocytes. The goal of stem cell-based regenerative medicine in cardiovascular disease, therefore, is to create healthy, functional cardiac cells that are able to integrate in the injured heart and restore its function.

In the past decades, several stem cell types have been discovered. These stem cells can be subdivided based on their differentiation capacity. Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are able to differentiate into all three embryonic germ layers, whereas multipotent stem cells can differentiate into a number of closely related cell types of a single embryonic germ layer. Cardiomyocytes were derived from several stem cell sources (). Other types of stem cells do not differentiate into cardiomyocytes themselves, but support cardiac repair by different mechanisms (). In this review, we will refer to all stem cell-derived cardiomyocytes and differentiated cell types enriched for cardiomyocytes as stem cell-derived cardiomyocytes (SCD-CMs), while we will refer to non-cardiomyocyte derivatives (such as vascular cells) as stem cell-derived cardiac support cells (SCD-CSCs).

Summary of stem cells used for cardiac repair.

Characteristics of stem cells studied for cardiac regeneration potential.

In this review, we will give an introduction to the principles of stem cell-based cardiac repair. Our aim is to give a concise up-to date overview of the therapeutic possibilities of stem cells for cardiac injury. First, we describe general requirements for stem cell therapy. After that, we will discuss in more detail the different stem cell sources and their therapeutic effects, since these vary for each cell type.

In order to be suitable for cardiac repair, stem cell-derived cardiac cells should resemble the original cardiac cell types and be able to integrate in the damaged heart. Integration requires administration of stem cell-derived cardiac cells at the right time using the right mode of delivery. Once delivered, transplanted cells need vascularization, electrophysiological coupling with the injured heart, and prevention of immunological rejection. Ideally there would also be beneficial effects on the host myocardium, for example, by stimulating proliferation or differentiation of local progenitors, neovascularization or by inhibiting apoptosis. The minimum requirement for the donor cells is to have no adverse effects. Finally, stem cell therapy needs to be safe, reproducible, and affordable. Each of these requirements will be discussed separately. ()

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Stem cells for cardiac repair: an introduction

here is epidemiological evidence that links type B coxsackie virus (CVB) infection with heart disease, and research published on July 31st in PLOS Pathogens now suggests a mechanism by which early infection impairs the heart's ability to tolerate stress at later stages of life.

CVB infection is very common and affects mostly children. The symptoms range widely: over half of the infections are thought to be asymptomatic, the majority of children who get sick have only a mild fever, and a very small proportion get inflammation of the heart or brain. On the other hand, 70 -- 80% of patients with heart failure show signs of a previous CVB infection but have no history of viral heart disease, raising the possibility that even a mild earlier infection makes them more vulnerable to get heart disease later on.

To investigate this, researchers from San Diego State University, USA, led by Roberta Gottlieb and Ralph Feuer, first established a mouse model of mild juvenile CVB infection. Mice infected with a non-lethal dose of the virus shortly after birth did not develop any heart disease symptoms during the infection or into adulthood, but they had a predisposition to heart disease later in life.

Detailed analysis of the mice after infection showed that the virus does indeed target the heart and is found in cardiac stem cells. When comparing the numbers of cardiac stem cells in previously infected adult mice with uninfected ones, the researchers found significantly smaller numbers in the infected mice.

To test whether the childhood infection and stem cell depletion had any effect on the adult heart, the researchers exposed infected mice to two different types of cardiac stress. They treated some of the mice with a drug known to overstimulate the heart, and they challenged another group by making them swim for 90 minutes every day for 14 days. Following both treatments, the infected mice showed clear signs of early heart disease whereas uninfected controls showed little or no symptoms.

Analyzing the stressed mice in more detail, the researchers found that the hearts from previously infected mice had impaired ability to re-arrange their heart blood vessels and grow new ones. This process, called vascular remodeling, is critical for the heart to respond to changes in the environment, including stress.

As discussed in the article, important open questions remain. For example, does CVB infection affect cardiac stem cells at any age, or is there a vulnerable period in early childhood? It is also not clear whether other strains of CVB have similar properties to the one used here, which was isolated from a patient with heart disease.

Nonetheless, the researchers conclude that their results "support the hypothesis that a mild CVB3 infection early in development can impair the heart's ability to undergo physiologic remodeling, leading to heart disease later in life." They also suggest that "the subtle cardiac alterations might go undetected under normal circumstances but emerge in the setting of increased demand such as intense exercise or chronic high blood pressure."

Story Source:

The above story is based on materials provided by PLOS. Note: Materials may be edited for content and length.

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Childhood coxsackie virus infection depletes cardiac stem cells, might compromise heart health in adults

PUBLIC RELEASE DATE:

31-Jul-2014

Contact: Roberta Gottlieb roberta.gottlieb@cshs.org PLOS

There is epidemiological evidence that links type B coxsackie virus (CVB) infection with heart disease, and research published on July 31st in PLOS Pathogens now suggests a mechanism by which early infection impairs the heart's ability to tolerate stress at later stages of life.

CVB infection is very common and affects mostly children. The symptoms range widely: over half of the infections are thought to be asymptomatic, the majority of children who get sick have only a mild fever, and a very small proportion get inflammation of the heart or brain. On the other hand, 70 80% of patients with heart failure show signs of a previous CVB infection but have no history of viral heart disease, raising the possibility that even a mild earlier infection makes them more vulnerable to get heart disease later on.

To investigate this, researchers from San Diego State University, USA, led by Roberta Gottlieb and Ralph Feuer, first established a mouse model of mild juvenile CVB infection. Mice infected with a non-lethal dose of the virus shortly after birth did not develop any heart disease symptoms during the infection or into adulthood, but they had a predisposition to heart disease later in life.

Detailed analysis of the mice after infection showed that the virus does indeed target the heart and is found in cardiac stem cells. When comparing the numbers of cardiac stem cells in previously infected adult mice with uninfected ones, the researchers found significantly smaller numbers in the infected mice.

To test whether the childhood infection and stem cell depletion had any effect on the adult heart, the researchers exposed infected mice to two different types of cardiac stress. They treated some of the mice with a drug known to overstimulate the heart, and they challenged another group by making them swim for 90 minutes every day for 14 days. Following both treatments, the infected mice showed clear signs of early heart disease whereas uninfected controls showed little or no symptoms.

Analyzing the stressed mice in more detail, the researchers found that the hearts from previously infected mice had impaired ability to re-arrange their heart blood vessels and grow new ones. This process, called vascular remodeling, is critical for the heart to respond to changes in the environment, including stress.

As discussed in the article, important open questions remain. For example, does CVB infection affect cardiac stem cells at any age, or is there a vulnerable period in early childhood? It is also not clear whether other strains of CVB have similar properties to the one used here, which was isolated from a patient with heart disease.

Continue reading here:
Childhood coxsackie virus infection depletes cardiac stem cells and might compromise heart health in adults

The future of medicine is regenerative medicine.

Thats a view shared by Thomas Gonwa, associate director of the Mayo Clinic Center for Regenerative Medicine in Jacksonville, and by Jorge and Leslie Bacardi.

Regenerative medicine will be the cutting-edge medicine of the 21st century, Gonwa says.

We think it is the most important thing happening in medicine, Leslie Bacardi said.

Now the Bacardis, who live in Nassau in the Bahamas, have given what Mayo Clinic officials call a substantial gift to fund ongoing research and clinical trials in regenerative medicine at the Mayo Clinic in Jacksonville.

Jorge Bacardi, part of the family that has been making rum and other spirits for 150 years, declined to specify the amount of the gift. Were not people who boast about the amount we give, he said.

Its an amount that should be sufficient to fund the ongoing research into regenerative medicine in Jacksonville, he said.

Doctors at the Mayo Clinic both in Jacksonville and in Rochester, Minn., now envision a future in which new organs can be grown for patients, using their own cells, and a time when the injection of stem cells can be used to repair a damaged organ.

Last year, Tim Nelson, a physician with the Center for Regenerative Medicine in Rochester, removed tissue from the arm of ABC Nightline reporter Bill Weir and created what Weir called a tiny piece of my cardiac tissue that had dramatically formed into the shape of a heart a pumping, three-dimensional glimpse into a future when this kind of cell could theoretically be injected into a heart-attack victim or a diseased child and literally mend the person from within.

That, to us, was just mind-boggling, Leslie Bacardi said. ... Regenerative medicine is for us an investment in our future and the future of medicine. It may take a while to reap any benefits, but when those benefits do come, it will make the investment seem small.

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Gift from Bacardi family will help Mayo Clinic researchers in Jacksonville close in on 'the future of medicine'

Washington No batteries required: Scientists are creating a biological pacemaker by injecting a gene into the hearts of sick pigs that changed ordinary cardiac cells into a special kind that induces a steady heartbeat.

The study, published Wednesday, is one step toward developing an alternative to electronic pacemakers that are implanted into 300,000 Americans each year.

There are people who desperately need a pacemaker but cant get one safely, said Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles, who led the work. This development heralds a new era of gene therapy that one day might offer them an option.

Your heartbeat depends on a natural pacemaker, a small cluster of cells its about the size of a peppercorn, Marban said that generates electrical activity. Called the sinoatrial node, it acts like a metronome to keep the heart pulsing at 60 to 100 beats per minute or so, more when youre active. If that node quits working correctly, hooking the heart to an electronic pacemaker works very well for most people.

But about 2 percent of recipients develop an infection that requires the pacemaker to be removed for weeks until antibiotics wipe out the germs, Marban said. And some fetuses are at risk of stillbirth when their heartbeat falters, a condition called congenital heart block.

For more than a decade, teams of researchers have worked to create a biological alternative that might help those kinds of patients, trying such approaches as using stem cells to spur the growth of a new sinoatrial node.

Marbans newest attempt uses gene therapy to reprogram a small number of existing heart muscle cells so that they start looking and acting like natural pacemaker cells instead.

Because pigs hearts are so similar to human hearts, Marbans team studied the approach in 12 laboratory pigs with a defective heart rhythm.

They used a gene named TBX18 that plays a role in the embryonic development of the sinoatrial node. Working through a vein, they injected the gene into some of the pigs hearts in a spot that doesnt normally initiate heartbeats and tracked them for two weeks.

Two days later, treated pigs had faster heartbeats than control pigs who didnt receive the gene, the researchers reported in the journal Science Translational Medicine. That heart rate automatically fluctuated, faster during the day. The treated animals also became more active, without signs of side effects.

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Scientists working on biological pacemaker

PUBLIC RELEASE DATE:

18-Jul-2014

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

Putnam Valley, NY. (July 18th 2014) The long-term, positive benefits of transplanted allogenic (other-donated) smooth muscle cells (SMCs) to repair cardiac tissues after myocardial infarction (MI) have been enhanced by the addition of interleukin 10 (IL-10) to the transplanted cells, report researchers in Canada. Their study with rats modeled with MI has shown that SMCs modified with IL-10 - a small, anti-inflammatory protein - benefitted cell survival, improved heart function, and also provided protection against the host's rejection of the allogenic SMCs.

The study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT1170Dhingra.

Three groups of rats modeled with MI were treated with SMC injections into the MI-damaged area of the heart. One group received unmodified autologous (self-donated) SMCs; a second group received unmodified allogenic (other-donated) SMCs; the third group received allogenic SMCs modified with IL-10. After three weeks, the unmodified autologous cells had engrafted while the unmodified allogenic cells had been rejected by the hosts. However, the IL-10-modified allogenic cells were found to greatly improve cell survival, improve ventricular function, increase myocardial wall thickness, and also prevent host immune response and rejection of the foreign cells.

"While the most appropriate cell type for cardiac repair remains controversial, mesenchymal stem cells (MSCs) that have been differentiated toward myogenic cells restore ventricular function better, as previous studies have shown," said study co-author Ren-Ke Li of the MaRS Centre in Toronto, Canada. "This study demonstrated that IL-10 gene-enhanced cell therapy prevented immune response, increased survival of SMCs in the heart, and improved cardiac function when compared to the results with the control groups."

The researchers noted that while the use of autologous SMCs donated by patients may be optimal for cell therapy, SMCs self-donated by older, debilitated patients who likely have other serious health problems, have limited regenerative capability. Thus, allogenic SMCs from young, healthy donors are the most beneficial cells, but rejection of foreign cells by the host has been a problem in allogenic cell transplantation. This study suggests that the use of allogenic SMCs modified with IL-10 can prevent host rejection.

"Future studies will be required to determine the long-term effects of IL-10 transduced SMCs to evaluate cell survival and cardiac function at six months and one year," concluded the researchers.

"The use of IL-10 overexpression to reduce rejection of allogenic SMCs is an interesting idea" said Dr. Amit N. Patel, director of cardiovascular regenerative medicine at the University of Utah and section editor for Cell Transplantation. "Further studies will help to determine if this manipulation could prove useful for translation of allogenic SMC therapies to humans".

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Interleukin-10 aids survival of cells transplanted to repair cardiac tissues after MI

WASHINGTON --

The study, published Wednesday, is one step toward developing an alternative to electronic pacemakers that are implanted into 300,000 Americans a year.

"There are people who desperately need a pacemaker but can't get one safely," said Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles, who led the work. "This development heralds a new era of gene therapy" that one day might offer them an option.

Your heartbeat depends on a natural pacemaker, a small cluster of cells - it's about the size of a peppercorn, Marban says - that generates electrical activity. Called the sinoatrial node, it acts like a metronome to keep the heart pulsing at 60 to 100 beats a minute or so, more when you're active. If that node quits working correctly, hooking the heart to an electronic pacemaker works very well for most people.

But about 2 percent of recipients develop an infection that requires the pacemaker to be removed for weeks until antibiotics wipe out the germs, Marban said. And some fetuses are at risk of stillbirth when their heartbeat falters, a condition called congenital heart block.

For over a decade, teams of researchers have worked to create a biological alternative that might help those kinds of patients, trying such approaches as using stem cells to spur the growth of a new sinoatrial node.

Marban's newest attempt uses gene therapy to reprogram a small number of existing heart muscle cells so that they start looking and acting like natural pacemaker cells instead.

Because pigs' hearts are so similar to human hearts, Marban's team studied the approach in 12 laboratory pigs with a defective heart rhythm.

They used a gene named TBX18 that plays a role in the embryonic development of the sinoatrial node. Working through a vein, they injected the gene into some of the pigs' hearts - in a spot that doesn't normally initiate heartbeats - and tracked them for two weeks.

Two days later, treated pigs had faster heartbeats than control pigs who didn't receive the gene, the researchers reported in the journal Science Translational Medicine. That heart rate automatically fluctuated, faster during the day. The treated animals also became more active, without signs of side effects.

Read the original here:
Scientists using gene therapy to create biological pacemaker

Case Study: Stem Cells vs Coronary Artery Bypass Surgery in a Patient with Multi-Vessel Disease 6 Year Follow Up

Stem cells outperform heart bypass surgery. A heart patient treated with his own stem cells instead of undergoing coronary bypass surgery is exceeding all expectations 6 years after his adult stem cell treatment.

In 2008, Howie Lindeman, then 58 years old, was facing open heart bypass surgery for three blocked coronary arteries. Lindeman, now 64, had his first heart attack at age 39 that severely damaged his heart. He went through multiple procedures over the last several years including having several stents placed in his blocked arteries. When he developed almost constant chest pain and struggled to walk just 25 feet his doctors decided to perform another heart catheterization. They found severe disease; two arteries were 100% blocked and the remaining one was at 80%. Cardiac bypass surgery was immediately recommended.

Lindeman was not quite ready to have his chest cracked open, so he sought alternative options. He was aware of successful treatments for single blocked arteries with stem cells. Determined to avoid surgery he inquired as to the possibility of stem cell treatment for his condition. Dr. Zannos Grekos, a cardiologist with Regenocyte, agreed to treat him as a case study with the understanding that if the treatment was not successful bypass surgery was his only option. Lindeman was treated with his own stem cells in March of 2008. Within one week of the stem cell procedure Lindeman was feeling much better and returned to fulltime work. His subsequent cardiac testing showed continued improvement up to one year later and now 6 years after his procedure he has had no further cardiac events, his heart tests have remained stable and he continues to work fulltime as a sound engineer touring the world.

I have a high stress, high energy job that I absolutely love, says Lindeman. The treatment has allowed me to continue my career and enjoy the active lifestyle I thought I had lost for good. Im a new person and I continue to feel better every day. Click here to see a video of Howie Lindeman.

The Regenocyte treatment is an outpatient procedure and after a period of observation, the patients then are typically discharged from the hospital. The patient is followed up regularly with testing to monitor their progress and measure their results. Lindemans follow up nuclear cardiac stress testing show a greater than 100% improvement in exercise capacity and improved myocardial perfusion. A heart catheterization performed a year after treatment showed a significant increase in heart function and new blood vessels. Lindemans progress was last reported in December 2011.

Dr. Grekos describes how stem cells are extracted from the patient and then processed in a laboratory. The stem cells are then activated and educated to heal the damaged heart. The lab process provides a key step in Regenocytes treatment success, Dr. Grekos explained. The lab extracts the stem cells from the sample and activates them into over a billion cells while educating them to assist the area of the body that needs treatment. These activated stem cells are known as Regenocytes (regenerative cells). The whole process takes about 3 days.

In this ground-breaking treatment, Dr. Zannos Grekos, an interventional cardiologist, inserted a catheter into Lindemans heart. Over the next 20 minutes, adult stem cells were introduced into the damaged part of his heart. The process of tissue repair begins almost immediately.

We continue to see remarkable results from adult stem cell treatment, said Grekos. Successes like those weve seen with Howie are common and show significant promise for diseases in other organs.

Dr. Grekos and the Regenocyte medical team continue to research the impact of adult stem cell therapy on heart disease. For more information on Regenocyte Adult Stem Cell procedures, upcoming seminars, and to see videos featuring Lindeman, visit http://www.regenocyte.com.

Original post:
Case Study: Stem Cells vs Coronary Artery Bypass Surgery in a Patient with Multi-Vessel Disease 6 Year Follow Up

Washington No batteries required: Scientists are creating a biological pacemaker by injecting a gene into the hearts of sick pigs that changed ordinary cardiac cells into a special kind that induces a steady heartbeat.

The study, published Wednesday, is one step toward developing an alternative to electronic pacemakers that are implanted into 300,000 Americans a year.

There are people who desperately need a pacemaker but cant get one safely, said Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles, who led the work. This development heralds a new era of gene therapy that one day might offer them an option.

Your heartbeat depends on a natural pacemaker, a small cluster of cells its about the size of a peppercorn, Marban says that generates electrical activity. Called the sinoatrial node, it acts like a metronome to keep the heart pulsing at 60 to 100 beats a minute or so, more when youre active. If that node quits working correctly, hooking the heart to an electronic pacemaker works very well for most people.

But about 2 percent of recipients develop an infection that requires the pacemaker to be removed for weeks until antibiotics wipe out the germs, Marban said. And some fetuses are at risk of stillbirth when their heartbeat falters, a condition called congenital heart block.

For over a decade, teams of researchers have worked to create a biological alternative that might help those kinds of patients, trying such approaches as using stem cells to spur the growth of a new sinoatrial node.

Marbans newest attempt uses gene therapy to reprogram a small number of existing heart muscle cells so that they start looking and acting like natural pacemaker cells instead.

Because pigs hearts are so similar to human hearts, Marbans team studied the approach in 12 laboratory pigs with a defective heart rhythm.

They used a gene named TBX18 that plays a role in the embryonic development of the sinoatrial node. Working through a vein, they injected the gene into some of the pigs hearts in a spot that doesnt normally initiate heartbeats and tracked them for two weeks.

Two days later, treated pigs had faster heartbeats than control pigs who didnt receive the gene, the researchers reported in the journal Science Translational Medicine. That heart rate automatically fluctuated, faster during the day. The treated animals also became more active, without signs of side effects.

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Scientists use gene therapy to create biological pacemaker

WASHINGTON (AP) -- No batteries required: Scientists are creating a biological pacemaker by injecting a gene into the hearts of sick pigs that changed ordinary cardiac cells into a special kind that induces a steady heartbeat.

The study, published Wednesday, is one step toward developing an alternative to electronic pacemakers that are implanted into 300,000 Americans a year.

"There are people who desperately need a pacemaker but can't get one safely," said Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles, who led the work. "This development heralds a new era of gene therapy" that one day might offer them an option.

Your heartbeat depends on a natural pacemaker, a small cluster of cells it's about the size of a peppercorn, Marban says that generates electrical activity. Called the sinoatrial node, it acts like a metronome to keep the heart pulsing at 60 to 100 beats a minute or so, more when you're active. If that node quits working correctly, hooking the heart to an electronic pacemaker works very well for most people.

But about 2 percent of recipients develop an infection that requires the pacemaker to be removed for weeks until antibiotics wipe out the germs, Marban said. And some fetuses are at risk of stillbirth when their heartbeat falters, a condition called congenital heart block.

For over a decade, teams of researchers have worked to create a biological alternative that might help those kinds of patients, trying such approaches as using stem cells to spur the growth of a new sinoatrial node.

Marban's newest attempt uses gene therapy to reprogram a small number of existing heart muscle cells so that they start looking and acting like natural pacemaker cells instead.

Because pigs' hearts are so similar to human hearts, Marban's team studied the approach in 12 laboratory pigs with a defective heart rhythm.

They used a gene named TBX18 that plays a role in the embryonic development of the sinoatrial node. Working through a vein, they injected the gene into some of the pigs' hearts in a spot that doesn't normally initiate heartbeats and tracked them for two weeks.

Two days later, treated pigs had faster heartbeats than control pigs who didn't receive the gene, the researchers reported in the journal Science Translational Medicine. That heart rate automatically fluctuated, faster during the day. The treated animals also became more active, without signs of side effects.

Continue reading here:
Scientists Try To Create Biological Pacemaker

........................................................................................................................................................................................

WASHINGTON No batteries required: Scientists are creating a biological pacemaker by injecting a gene into the hearts of sick pigs that changed ordinary cardiac cells into a special kind that induces a steady heartbeat.

The study, published Wednesday, is one step toward developing an alternative to electronic pacemakers that are implanted into 300,000 Americans a year.

There are people who desperately need a pacemaker but cant get one safely, said Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles, who led the work. This development heralds a new era of gene therapy that one day might offer them an option.

Your heartbeat depends on a natural pacemaker, a small cluster of cells its about the size of a peppercorn, Marban says that generates electrical activity. Called the sinoatrial node, it acts like a metronome to keep the heart pulsing at 60 to 100 beats a minute or so, more when youre active. If that node quits working correctly, hooking the heart to an electronic pacemaker works very well for most people.

But about 2 percent of recipients develop an infection that requires the pacemaker to be removed for weeks until antibiotics wipe out the germs, Marban said. And some fetuses are at risk of stillbirth when their heartbeat falters, a condition called congenital heart block.

For over a decade, teams of researchers have worked to create a biological alternative that might help those kinds of patients, trying such approaches as using stem cells to spur the growth of a new sinoatrial node.

Marbans newest attempt uses gene therapy to reprogram a small number of existing heart muscle cells so that they start looking and acting like natural pacemaker cells instead.

Because pigs hearts are so similar to human hearts, Marbans team studied the approach in 12 laboratory pigs with a defective heart rhythm.

They used a gene named TBX18 that plays a role in the embryonic development of the sinoatrial node. Working through a vein, they injected the gene into some of the pigs hearts in a spot that doesnt normally initiate heartbeats and tracked them for two weeks.

Read more:
Scientists creating a biological pacemaker

Freeport, Bahamas (PRWEB) July 15, 2014

Okyanos Heart Institute, a leader in cardiac adult stem cell therapy, has selected Perkins Healthcare Technologies to provide video integration solutions for its new state-of-the-art cardiac catheterization lab. The video integration system is paired with Phillips equipment, creating a top-grade comprehensive solution for the cath lab by providing the ability to view high definition clinical cardiac procedures video information on a large screen collaged layout 8-megapixel display. Built to US surgical standards, the lab equipment is being installed over the next few weeks, bringing the highest standard of care and most advanced technology to cardiac care.

Okyanos Heart Institute utilizes adult stem cells derived from ones own adipose (fat) tissue, placing them in the heart to help it repair damaged or diseased tissue. This is done using a minimally invasive catheterization procedure, as demonstrated in multiple rigorous clinical trials from around the world.

Okyanos Chief Medical Officer Howard T. Walpole, Jr., M.D., M.B.A., F.A.C.C., F.A.C.A.I. noted, The most important functions of the video integration system are to provide high quality images with the right projections of the image. When you visualize a heart, you need to be able to get a complex angle to see the back side of the heart. This enables the cardiologist to deliver the stem cells where they are most needed. The size of the image detector is smaller and the more flexible positioner makes it easier to pivot around the patients body to obtain those difficult views.

Perkins Healthcare Technologies has been providing clinical video integration solutions for over 25 years and looks forward to bringing its expertise to Okyanos Heart Institute. We are very excited to have our state-of-the-art video integration system included as a part of this innovative solution for cardiac care. Our video integration system provides Okyanos a flexible solution to meet its staff needs, said Steve Plaugher, COO of Perkins Healthcare Technologies. Instead of having to assimilate patient data from multiple sources and locations, the staff can now access and view this information in their respective work area in an instant.

The combination of Okyanos adult stem cell treatments and Perkins state-of-the-art video integration solutions are designed to enhance patient care, improve the quality of life and deliver an exceptional patient experience.

To learn more about Okyanos and cardiac stem cell therapy, take a few minutes to view this video or visit http://www.Okyanos.com.

To learn more about Perkins and its clinical video integration and control technology, visit http://www.PerkinsHealthcareTechnologies.com for information on Perkins Solutions.

About Okyanos Heart Institute: (Oh key AH nos) Based in Freeport, Grand Bahama, Okyanos Heart Institutes mission is to bring a new standard of care and a better quality of life to patients with coronary artery disease using cardiac stem cell therapy. Okyanos adheres to U.S. surgical center standards and is led by CEO Matt Feshbach and Chief Medical Officer Howard T. Walpole Jr., M.D., M.B.A., F.A.C.C., F.A.C.A.I. Okyanos Treatment utilizes a unique blend of stem and regenerative cells derived from ones own adipose (fat) tissue. The cells, when placed into the heart via a minimally-invasive catheterization, stimulate the growth of new blood vessels, a process known as angiogenesis. Angiogenesis facilitates blood flow in the heart and supports intake and use of oxygen (as demonstrated in rigorous clinical trials such as the PRECISE trial). The literary name Okyanos, the Greek god of rivers, symbolizes restoration of blood flow.

About Perkins Healthcare Technologies: Perkins Healthcare Technologies has designed, developed, manufactured and distributed clinical video integration solutions for more than 25 years. Perkins vendor neutral video integration solutions work seamlessly with new or existing imaging, surgical, or hybrid procedure suites; complementing the functionality, improving workflow, and providing critical patient information to the stakeholder where and when they need it.

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Okyanos & Perkins Partner for Cardiac Stem Cell Therapy Innovation

What Is Cardiac Cell Therapy?

In its simplest form, cardiac cell therapy is simply the use of stem cells to regenerate new heart tissue. Stem cells were originally used to grow your heart before you were born. Stem cells capable of growing new heart tissue reside in all of us. Through the use of trial-tested technologies, your own stem cells can be used to grow and repair your cardiac tissue.

The most difficult aspect of this therapy was developing a way to isolate your stem cells and put them to use to grow new heart tissue. And thanks to years of research, this process has been developed and tested in clinical trials with favorable results.

What Is The Procedure?

There is a wide variety of methods of placing stem cells in the body or near the organ they are intended to help. One procedure tested under trial is through the use of catheters (a specialized tube) and is being implemented in a new state-of-the-art clinic by a U.S. licensed veteran cardiologist. This process requires only a local anesthetic and minimal recovery time (hours vs days). And your own cardiologist is consulted closely to make sure you are a good candidate for the procedure and to monitor your improvements when you return home.

If you'd like our recommendations on qualified cardiac stem cell clinics, please don't hesitate to contact us at info@heartcell.org. We'd be happy to connect you to a clinic, doctor or stem cell patient for you to explore your options further.

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What Is Stem Cell Therapy | Stem Cell For Heart | Cardiac ...

Council of Scientific and Industrial Research (CSIR) Centre for Cellular and Molecular Biology (CCMB) Director, Dr Ch. Mohan Rao today claimed that the heart disease can be treated without surgeries in future.

Addressing after inaugurating the 19th Annual conference of the Cardiological Society of India (CSI-AP Chapter) here, Dr Rao said that in the recent research in molecular biology found that 'heart' too have 'stem cells' which will help to automatically build the damaged part of any organ.

He said that further research also going with collaboration of other foreign institutions on how to bring the 'stem cells' out and repair.

Once the solution is found, the cardiac diseases can be healed with surgery, Dr Rao said.

''This development will make the stem cell based therapy replace the chemical based therapy in Cardiology,'' he added.

Irregular eating habits and busy lifestyle are among the major causes of the cordial illness, he said and advised to the youth to follow healthy lifestyle to avoid heart related problems.

While talking about the latest research, he said, ''To reduce the deaths due to cardiac illness the CCMB is working along with the scientists from Japan, the US and Italy to develop the an easier way to treatment.''

Dr Rao also given a clarion call to Cardiology experts to come forward for joint research on cardiac problems.

Encouraging the research in Cardiology, Dr Rao also invited the young medicos to visit the CCMB campus and work with the institute.

Discussing various kinds of heart diseases, he said, ''Dilated Cardiomyopathy is one of the most common heart disease among the children.''

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Cardiac diseases to be treated without surgeries soon as stem cells found

By Ben Spencer

Published: 09:48 EST, 4 July 2014 | Updated: 10:20 EST, 4 July 2014

Fat removed from a heart attack patient during cardiac surgery could be re-injected into their chest to lower the risk of repeat problems, research suggests.

Scientists think that stem cells in fatty tissue could be extracted and inserted directly into the heart, reducing the chance of future attacks.

The stem cells - blank cells capable of acting as a repair kit for the body by replacing worn-out tissue - can improve the functioning of the heart and strengthen crucial arteries and veins, the researchers found.

Usually most of the fat that is found during open heart surgery is removed and then discarded.

Scientists believe fat removed from a heart attack patient during cardiac surgery could be re-injected into their chest to lower the risk of repeat problems. Stock image

But the new study suggests that the fat could be retained and the useful stem cells isolated and injected back into the heart - all while the patient is still on the operating table.

Canadian cardiologist Dr Ganghong Tian, who will present his findings at a European Society of Cardiology conference in Barcelona tomorrow (Sunday), said: During cardiac surgery fat tissue may need to be removed from patients to expose the heart.

We were intrigued to find out whether this mediastinal fat, which would otherwise be discarded, contained stem cells that could be injected back into the heart before closing the chest.

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Fat cells removed from heart attack patients could be re-injected into their chest to help repair the organ ...

By Jim Kasuba The News-Herald Twitter: @JKasuba

Elizabeth Disney (left) turned out to be a suitable blood stem donor for her sister, Brittany, who is afflicted with Burkitt lymphoma, considered to be an extremely rare disease for a young woman of only 23. Photo courtesy of Donna Smith

RIVERVIEW Battling a rare cancer has been a rough road for Brittany Disney, but the worst may be behind her.

The good news is that a suitable stem cell donor has been found and the transplant surgery went well. The not-so-good news is that theres a long recovery period and shes still in a lot of pain.

Donna Smith, a close friend of the family, said the young woman underwent stem cell replacement on June 6.

There was a one in four chance that a sibling would be a match, Smith said. (Her sister) Elizabeth had five out of six markers to be a stem cell donor for her.

Disney, 23, was diagnosed late last year with stage four Burkitt lymphoma, a form of non-Hodgkins lymphoma in which cancer starts in immune cells called B-cells. Recognized as the fastest growing human tumor, Burkitt lymphoma is associated with impaired immunity and is rapidly fatal if left untreated.

Burkitt lymphoma is so rare in young adult women that the Henry Ford Health System wrote about the case in a medical journal, said one of Disneys college friends.

In November, friends and family sponsored a spaghetti dinner fundraiser to assist the family with medical bills and expenses, but things continued to look bleak, as a stem cell transplant appeared to be the only answer to treating the condition.

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Riverview woman recovers from stem cell transplant; family seeking notes of encouragement

WASHINGTON Scientists have come up with a bright idea to repair teeth And they say their concept using laser light to entice the bodys own stem cells into action may offer enormous promise beyond just dentistry in the field of regenerative medicine.

The researchers used a low-power laser to coax dental stem cells to form dentin, the hard tissue that makes up most of a tooth, in studies involving rats and mice and using human cells in a laboratory. The study appeared in the journal Science Translational Medicine.

They did not regenerate an entire tooth in part because the enamel part was too tricky. But merely getting dentin to grow could help alleviate the need for root canal treatment, the painful procedure to remove dead or dying nerve tissue and bacteria from inside a tooth, they said.

Im a dentist by training. So I think it has potential for great impact in clinical dentistry, researcher Praveen Arany of the National Institute of Dental and Craniofacial Research, part of the U.S. National Institutes of Health, said Friday. Arany expressed hope that human clinical trials could get approval in the near future.

Our treatment modality does not introduce anything new to the body, and lasers are routinely used in medicine and dentistry, so the barriers to clinical translation are low, added Harvard University bioengineering professor David Mooney. It would be a substantial advance in the field if we can regenerate teeth rather than replace them.

Using existing regeneration methods, scientists must take stem cells from the body, manipulate them in a lab and put them back into the body. This new technique stimulates action in stem cells that are already in place.

Scientists had long noticed that low-level laser therapy can stimulate biological processes like rejuvenating skin and stimulating hair growth but were not sure of the mechanisms. Arany noted the importance of finding the right laser dose, saying: Too low doesnt work and too high causes damage.

The researchers found that laser exposure of the tooth at the right intensity prompted certain oxygen-containing molecules to activate a cell protein that is known to be involved in development, healing and immune functions.

This protein in turn directed stem cells present in tooth pulp to turn into dentin. Stem cells are master cells that are capable of transforming into various types of tissues in the body.

The question is whether using this method could get other stem cells to become useful in laser-induced regenerative medicine. Arany said he is hopeful it can be used in healing wounds, regenerating cardiac tissue, dealing with inflammation issues and fixing bone damage, among other applications.

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Meeri N. Kim, For The Inquirer Last updated: Sunday, May 18, 2014, 8:51 AM Posted: Saturday, May 17, 2014, 3:55 PM

Imagine a document 25,000 words long - about 100 pages, double-spaced - with one small error. Within the text of our genetic code, a single change like this can lead to a life-threatening disease such as sickle-cell anemia or cystic fibrosis.

Most of these single-gene disorders have no cure. But using a new technique, doctors may one day be able to correct the genetic typo by replacing a harmful mutation in the genome with healthy DNA.

Introducing CRISPR (clustered regularly interspaced short palindromic repeats), a genetic editing tool that can cut and paste parts of any living animal's DNA. Although in its infancy, the system is generating excitement among scientists for its ease of use, accessibility, and vast potential.

The CRISPR system enables researchers to make a small chain of custom-made molecules, called a guide RNA, and a Cas9 enzyme. The guide RNA is like the search function of a word processor, running along the length of the genome until it finds a match; then, the scissorslike Cas9 cuts the DNA. CRISPR can be used to delete, insert, or replace genes.

"We didn't used to think that we had the tools to correct mutation in humans," said Penn Medicine cardiologist Jonathan Epstein, who just began using the technique in his lab. "The advantage of CRISPR is that we can."

For instance, sickle-cell anemia is caused by a mutation in chromosome 11 that causes red blood cells to be crescent-shaped, sticky, and stiff. They end up stuck in the blood vessels, keeping enough oxygen from reaching the body. While the disease can be treated with bone marrow or stem cell transplants, most patients cannot find well-matched donors.

Here's where CRISPR can help. Biomedical engineer Gang Bao of the Georgia Institute of Technology aims to use the system to repair the DNA of a patient's own stem cells, so no outside donor would be needed. The stem cells would be extracted from the patient's bone marrow, their mutations replaced with normal DNA, and inserted back in. The hope is that the gene-corrected stem cells would then begin making normal red blood cells.

The treatment works in mice, and Bao foresees human trials within a few years.

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Genetic 'typo' corrector

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Washington, May 12 : Researchers have merged stem cell and 'organ-on-a-chip' technologies to grow, for the first time, functioning human heart tissue carrying an inherited cardiovascular disease.

The research appears to be a big step forward for personalized medicine, as it is working proof that a chunk of tissue containing a patient's specific genetic disorder can be replicated in the laboratory.

Using their interdisciplinary approach, the investigators modeled the cardiovascular disease Barth syndrome, a rare X-linked cardiac disorder caused by mutation of a single gene called Tafazzin, or TAZ. The disorder, which is currently untreatable, primarily appears in boys, and is associated with a number of symptoms affecting heart and skeletal muscle function.

The researchers took skin cells from two Barth syndrome patients, and manipulated the cells to become stem cells that carried these patients' TAZ mutations. Instead of using the stem cells to generate single heart cells in a dish, the cells were grown on chips lined with human extracellular matrix proteins that mimic their natural environment, tricking the cells into joining together as they would if they were forming a diseased human heart.

The engineered diseased tissue contracted very weakly, as would the heart muscle seen in Barth syndrome patients.

The investigators then used genome editinga technique pioneered by Harvard collaborator George Church, PhDto mutate TAZ in normal cells, confirming that this mutation is sufficient to cause weak contraction in the engineered tissue.

On the other hand, delivering the TAZ gene product to diseased tissue in the laboratory corrected the contractile defect, creating the first tissue-based model of correction of a genetic heart disease.

Furthermore, the scientists discovered that the TAZ mutation works in such a way to disrupt the normal activity of mitochondria, often called the power plants of the cell for their role in making energy.

However, the mutation didn't seem to affect overall energy supply of the cells. In what could be a newly identified function for mitochondria, the researchers describe a direct link between mitochondrial function and a heart cell's ability to build itself in a way that allows it to contract.

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Stem cell and 'organ-on-a-chip' merger step forward for personalized meds

PUBLIC RELEASE DATE:

11-May-2014

Contact: Joseph Caputo joseph_caputo@harvard.edu 617-496-1491 Harvard University

Cambridge, MAHarvard scientists have merged stem cell and 'organ-on-a-chip' technologies to grow, for the first time, functioning human heart tissue carrying an inherited cardiovascular disease. The research appears to be a big step forward for personalized medicine, as it is working proof that a chunk of tissue containing a patient's specific genetic disorder can be replicated in the laboratory.

The work, published in Nature Medicine, is the result of a collaborative effort bringing together scientists from the Harvard Stem Cell Institute, the Wyss Institute for Biologically Inspired Engineering, Boston Children's Hospital, the Harvard School of Engineering and Applied Sciences, and Harvard Medical School. It combines the 'organs-on-chips' expertise of Kevin Kit Parker, PhD, and stem cell and clinical insights by William Pu, MD.

Using their interdisciplinary approach, the investigators modeled the cardiovascular disease Barth syndrome, a rare X-linked cardiac disorder caused by mutation of a single gene called Tafazzin, or TAZ. The disorder, which is currently untreatable, primarily appears in boys, and is associated with a number of symptoms affecting heart and skeletal muscle function.

The researchers took skin cells from two Barth syndrome patients, and manipulated the cells to become stem cells that carried these patients' TAZ mutations. Instead of using the stem cells to generate single heart cells in a dish, the cells were grown on chips lined with human extracellular matrix proteins that mimic their natural environment, tricking the cells into joining together as they would if they were forming a diseased human heart. The engineered diseased tissue contracted very weakly, as would the heart muscle seen in Barth syndrome patients.

The investigators then used genome editinga technique pioneered by Harvard collaborator George Church, PhDto mutate TAZ in normal cells, confirming that this mutation is sufficient to cause weak contraction in the engineered tissue. On the other hand, delivering the TAZ gene product to diseased tissue in the laboratory corrected the contractile defect, creating the first tissue-based model of correction of a genetic heart disease.

"You don't really understand the meaning of a single cell's genetic mutation until you build a huge chunk of organ and see how it functions or doesn't function," said Parker, who has spent over a decade working on 'organs-on-chips' technology. "In the case of the cells grown out of patients with Barth syndrome, we saw much weaker contractions and irregular tissue assembly. Being able to model the disease from a single cell all the way up to heart tissue, I think that's a big advance."

Furthermore, the scientists discovered that the TAZ mutation works in such a way to disrupt the normal activity of mitochondria, often called the power plants of the cell for their role in making energy. However, the mutation didn't seem to affect overall energy supply of the cells. In what could be a newly identified function for mitochondria, the researchers describe a direct link between mitochondrial function and a heart cell's ability to build itself in a way that allows it to contract.

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Patient stem cells used to make 'heart disease-on-a-chip'