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

Harvard 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 editing -- a technique pioneered by Harvard collaborator George Church, PhD -- to 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.

"The TAZ mutation makes Barth syndrome cells produce an excess amount of reactive oxygen species or ROS -- a normal byproduct of cellular metabolism released by mitochondria -- which had not been recognized as an important part of this disease," said Pu, who cares for patients with the disorder.

"We showed that, at least in the laboratory, if you quench the excessive ROS production then you can restore contractile function," Pu added. "Now, whether that can be achieved in an animal model or a patient is a different story, but if that could be done, it would suggest a new therapeutic angle."

His team is now trying to translate this finding by doing ROS therapy and gene replacement therapy in animal models of Barth syndrome to see if anything could potentially help human patients. At the same time, the scientists are using their human 'heart disease-on-a-chip' as a testing platform for drugs that are potentially under trial or already approved that might be useful to treat the disorder.

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

'Heart Disease-On-A-Chip' Made From Patient Stem Cells

Image Caption: Researchers use modified RNA transfection to correct genetic dysfunction in heart stem cells derived from Barth syndrome patients. The series of images show how inserting modified RNA into diseased cells causes the cells to produce functioning versions of the TAZ protein (first image: in green) that correctly localize in the mitochondria (second image: in red). When the images are merged to demonstrate this localization, green overlaps with red, giving the third image a yellow color. Credit: Gang Wang and William Pu/Boston Children's Hospital

[ Watch The Video: Cardiac Tissue Contractile Strength Differences Shown Using Heart-On-A-Chip ]

Harvard University

Harvard 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 patients 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 Childrens 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 dont really understand the meaning of a single cells genetic mutation until you build a huge chunk of organ and see how it functions or doesnt 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 thats 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 didnt 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 cells ability to build itself in a way that allows it to contract.

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'Heart Disease-On-A-Chip' Made From Patient Stem Cells

BioTime Announces First Quarter 2014 Results and Recent Developments

ALAMEDA, Calif.--(BUSINESS WIRE)--BioTime, Inc. (NYSE MKT: BTX) today reported financial results for the first quarter ended March 31, 2014 and highlighted recent corporate accomplishments.

BioTimes efforts in the first quarter of 2014 were focused on advancing near-term products through clinical trials while also preparing certain novel stem cell-based therapeutics for clinical trials later this year. Enrollment in three diagnostic clinical studies has remained rapid, with completion expected later in 2014. Following the successful safety trial of ReneviaTM, we have made rapid progress in preparing for the pivotal ReneviaTM trial during the second half of the year, said Michael D. West, Ph.D., BioTimes Chief Executive Officer. At our subsidiary Asterias Biotherapeutics, we have been preparing to initiate a new Phase 1/2a clinical trial of OPC1 for the treatment of spinal cord injury in 2014, pending clearance from the FDA, and also preparing our VAC2 cancer vaccine for a potential clinical trial. Also in the quarter, BioTimes subsidiary Cell Cure Neurosciences Ltd. advanced preclinical development of OpRegen for a planned IND filing in 2014 for the treatment of age-related macular degeneration.

We have continued to develop our subsidiaries businesses, commented Dr. West. Shares of the Series A common stock of our subsidiary Asterias Biotherapeutics, Inc. are now scheduled to begin trading publicly this summer following Gerons distribution of those shares to its stockholders, for which a record date of May 28th has been set. We were also pleased to recently announce that LifeMap Solutions, Inc., a newly organized subsidiary of our LifeMap Sciences, Inc., has entered into an agreement with a major medical center to create innovative mobile health (mHealth) products powered by biomedical and other personal big data.

As the industry leader in regenerative medicine with over 600 patents and patent applications worldwide, BioTime and its subsidiaries have assembled a broad array of strategically important regenerative medicine technologies and assets for the development of therapeutic and diagnostic products, Dr. West continued. Our expenditure levels were higher than usual during the fourth quarter and the recently ended first quarter, but our recent progress in streamlining our workforce through shared core resources among our subsidiaries should reduce our cash burn rate and optimize value for our shareholders during this exciting time in the companys history. We would like to thank our long-term investors for their continued support and our collaborators at leading academic medical institutions for their help in advancing our products toward our goal of helping patients who have serious unmet medical needs.

First Quarter and Recent Highlighted Corporate Accomplishments

Financial Results

Revenue

For the quarter ended March 31, 2014, on a consolidated basis, total revenue was $1.1 million, up $0.5 million from $0.6 million for the same period one year ago. The increase in first quarter revenue is primarily attributable to grant income awarded to BioTimes subsidiary Cell Cure Neurosciences Ltd. from Israels Office of the Chief Scientist.

Expenses

Operating expenses for the three months ended March 31, 2014 were $12.1 million, compared to expenses of $8.8 million for the same period of 2013. The increase in operating expenses is primarily attributable to an increase in staffing and the expansion of research and development efforts of Asterias and the amortization expense of intangible assets recorded in connection with the Geron stem cell asset acquisition in October 2013.

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BioTime Announces First Quarter 2014 Results and Recent Developments

Top Northern Colorado Pain Management Doctors at Colorado Clinic Now Offering Stem Cell Procedures for Degenerative …

Boulder, Colorado (PRWEB) May 13, 2014

Colorado Clinic, the top pain management clinics in Greeley, Boulder and Loveland, is now offering nonoperative stem cell procedures to help relieve degenerative arthritis pain and avoid the need for joint replacement surgery. The procedures are offered by a Double Board Certified Colorado pain management doctor, with multiple options for the procedures. For more information and scheduling, call (303) 444-4141.

Currently in America there are over 1 million joint replacement procedures performed annually. This includes joint replacement for the shoulder, hip, knee and ankle. While these procedures typically work very well, they are truly meant as a last resort option since there are several risks involved with the operation. One of the main risks is that the implants used in joint replacement are not meant to last forever and revision surgeries are much more complicated than the initial. Therefore, joint replacement should be avoided for as long as possible.

Stem cell procedures are cutting-edge and now mainstream for helping repair arthritic damage in joints and providing pain relief from arthritis. Dr. Brad Sisson is a highly qualified pain management doctor at Colorado Clinic, and performs the outpatient stem cell procedures with either amniotic derived or bone marrow derived stem cells.

The amniotic fluid is obtained from consenting donors after a scheduled C-section, and has been shown to have a very high concentration of stem cells. The fluid is processed at an FDA regulated lab and contains no embryonic stem cells or fetal material. This alleviates any ethical concerns.

The bone marrow derived stem cells are harvested from the patient, and then are immediately processed to concentrate the stem cells, growth factors and platelets to inject into the area being treated.

To date, small published studies have shown excellent benefits for degenerative arthritis with stem cell procedures. Dr. Sisson performs the regenerative medicine treatments as an outpatient, and there is minimal risk involved with either of the procedures.

Colorado Clinic has several pain management centers in Northern Colorado including Boulder, Greeley and Loveland. Patients are currently being accepted at all of the locations for the stem cell procedures. For more information and scheduling with pain management Boulder trusts, call (303) 444-4141.

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Top Northern Colorado Pain Management Doctors at Colorado Clinic Now Offering Stem Cell Procedures for Degenerative ...

Top Beverly Hills Pain Management Doctors at BZ Pain Now Offering Stem Cell Procedures for Joint Arthritis for Pain …

Beverly Hills, California (PRWEB) May 12, 2014

The top Beverly Hills pain management doctors at BZ Pain are now offering stem cell procedures for those with joint arthritis and pain. The outpatient regenerative medicine procedures are typically able to relieve pain and help patients avoid the need for joint replacement surgery of the shoulder, hip, knee and ankle. Call (310) 626-1526 for more information and scheduling.

Over a million joint replacement procedures are performed each year in America. These procedures should be considered an absolute last resort, since the implants are not meant to last forever. There are potential complications with joint replacement.

Therefore, stem cell procedures are an excellent option. They often help repair and regenerate damaged tissue, which is very different than what occurs with steroid injections. The stem cell procedures include options derived from amniotic fluid, fat tissue, or one's bone marrow.

Initial studies are showing the benefits of stem cell procedures for degenerative arthritis. With exceptionally low risk, there is a significant upside with the stem cell pain management therapies.

Dr. Zarrini at BZ Pain is a Double Board Certified Los Angeles pain management doctor, and is able to provide both medical and interventional therapies. The procedures do not involve any fetal tissue or embryonic stem cells. The procedures may help degenerative disease symptoms in the shoulder, hip, knee and ankle to name a few joints.

For those interested in stem cell therapy Los Angeles and Beverly Hills trusts, call BZ Pain today at (310) 626-1526.

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Top Beverly Hills Pain Management Doctors at BZ Pain Now Offering Stem Cell Procedures for Joint Arthritis for Pain ...

Cord Banking, Cell Therapy Helps Treat Deadly Diseases

SPRINGFIELD, Mo. -- A child with a life threatening disease is heart wrenching for parents. Suddenly they are faced with no easy way to get a match for stem cells that could save their child.

With cell therapy, there is a way to do that but it starts in the delivery room.

Delanie Rinne's fourth child, Ezekial, was born earlier this year and even though he'll get older; proof of that day is being stored at Core23 BioBank in Springfield.

"We decided to look into banking the cord blood because we know that this is probably our last biological child," says Rinne.

Core23 stores your child's blood, plasma or tissue from the umbilical cord to help treat 81 different diseases.

"If I had a child that has Leukemia and I was pregnant then that would be a treatment option."

Emily and Michael Perry opened the private cord bank as another option for parents.

"We see that cell therapy is surpassing bone marrow, we truly believe that it is the medicine of the future."

"Cell therapy is taking a healthy, viable cell and putting it into somebody's body to treat a disease or a condition."

The process starts in the delivery room and ends in a hydrogen tank in their lab.

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Cord Banking, Cell Therapy Helps Treat Deadly Diseases

Neil Riordan, PhD Presents at American Academy of Anti-Aging Medicine's 22nd Annual World Congress on Anti-Aging …

Orlando, FL (PRWEB) May 13, 2014

Neil Riordan, PhD will Present Umbilical Cord Mesenchymal Stem Cells (MSC) in the Treatment of Autoimmune Diseases at the 22nd Annual World Congress on Anti-Aging, Regenerative and Aesthetic Medicine at the Gaylord Palms Hotel in Orlando, Florida as part of the Specialty Workshop: Stem Cells in Anti-Aging Medicine: An Update.

The primary focus of this workshop is to teach medical professionals how to successfully incorporate stem cell treatments into their practices. Expert faculty will cover stem cell theory and clinical trial research for all aspects of regenerative medicine as well as stem cell treatment marketing.

Dr. Riordan will discuss: Allogeneic mesenchymal stem cells mechanisms of immune modulating activities; the importance of MSC placement for clinical effect; human clinical trials demonstrating efficacy; alternative routes of MSC delivery; dose and frequency; and clinical safety of MSC.

The conference will be held from May 15 17, 2014 at the Gaylord Palms Hotel in Orlando, Florida. For more information, please visit http://www.a4m.com/anti-aging-conference-orlando-2014-may.html.

About Neil Riordan PhD

Dr. Riordan is the founder and chairman of Medistem Panama, Inc., (MPI) a leading stem cell laboratory and research facility located in the Technology Park at the prestigious City of Knowledge in Panama City, Panama. Founded in 2007, MPI stands at the forefront of applied research on adult stem cells for several chronic diseases. MPI's stem cell laboratory is ISO 9001 certified and fully licensed by the Panamanian Ministry of Health. Dr. Riordan is the founder of Stem Cell Institute (SCI) in Panama City, Panama (est. 2007).

Under the umbrella of MPI subsidiary Translational Biosciences, MPI and SCI are currently conducting five IRB-approved clinical trials in Panama for multiple sclerosis, rheumatoid arthritis and osteoarthritis using human umbilical cord-derived mesenchymal stem cells, mesenchymal trophic factors and stromal vascular fraction. Additional trials for spinal cord injury, autism and cerebral palsy are slated to commence in 2014 upon IRB approval.

Dr. Riordan is an accomplished inventor listed on more than 25 patent families, including 11 issued patents. He is credited with a number of novel discoveries in the field of cancer research since the mid-1990s when he collaborated with his father Dr. Hugh Riordan on the effects of high-dose intravenous vitamin C on cancer cells and the tumor microenvironment. This pioneering study on vitamin Cs preferential toxicity to cancer cells notably led to a 1997 patent grant for the treatment of cancer with vitamin C. In 2010, Dr. Riordan received another patent for a new cellular cancer vaccine.

Dr. Riordan is also the founder of Aidan Products, which provides health care professionals with quality nutraceuticals including Stem-Kine, the only nutritional supplement that is clinically proven to increase the amount of circulating stem cells in the body for an extended period of time. Stem-Kine is currently sold in 35 countries.

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Neil Riordan, PhD Presents at American Academy of Anti-Aging Medicine's 22nd Annual World Congress on Anti-Aging ...

Stem cell treatments reaching patients

Neurosurgeon and stem cell researcher, Joseph Ciacci M.D. will soon start a clinical trial of stem cells to treat paralysis from spinal cord injury.

After many years of waiting, a flood of new regenerative-cell therapies is finally reaching patients. Hundreds of clinical trials for these experimental treatments are under way across the world.

In the United States, 774 trials with stem or other regenerative cells are open to patients or soon will be, according to clinicaltrials.gov, which lists government-approved clinical testing in this country and abroad. Of that total, 147 are taking place in California.

One of the most difficult tests involving stem cells repairing spinal-cord damage that has caused complete loss of movement and sensation below the injury site is set to begin soon at UC San Diego.

Patients in that study will get injections of fetal-derived neural stem cells in and around the injury site, along with physical therapy and immune-system drugs in case theres a reaction to the stem cells. The trial will use a device that delivers precisely targeted micro-injections of cells to the targeted areas.

The clinical trial will test safety and look for early signs of efficacy, said Dr. Joseph Ciacci, a UC San Diego neurosurgeon leading the testing.

A study published a year ago found that in rats with spinal-cord injuries, the neural stem cells significantly improved movement in the hind paws. Ciacci, who co-authored that study, saw the cells proliferate and fill in a spinal-cord cavity that had resulted from the injuries. Such results supported testing the therapy in people, he said, but he declined to say whether he expected to see any improvement in those patients.

I really dont know, because its not been done, Ciacci said.

The clinical trial is expected to start in June. Its intended for adults 18 to 65 years old who suffered their injury at least one year ago but no more than two years ago. For more information, visit utsandiego.com/ucsdspinal or call Amber Faulise at (858) 657-5175.

Another type of stem cells, mesenchymal stromal, might be described as the duct tape of regenerative cells. Generally derived from bone marrow, they are being tested for treatment of pulmonary fibrosis, multiple sclerosis, kidney transplants, liver cirrhosis, osteoarthritis of the knee, stroke and many other conditions. Worldwide, 226 trials are being conducted with these cells, including 45 in the U.S. and 12 in California, according to clinicaltrials.gov.

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Stem cell treatments reaching patients

Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory …

We did this randomised, open-label, phase 2 study at seven German transplantation centres. We enrolled patients with aggressive B-cell or T-cell lymphoma and primary refractory disease, early relapse (2), busulfan (12 mg/kg oral or 96 mg/kg intravenous), and cyclophosphamide (120 mg/kg) was followed by allogeneic stem-cell transplantation. Patients were randomly assigned (1:1) to receive rituximab (375 mg/m2 on days 21, 28, 35, 42, 175, 182, 189, and 196) or not. Allocation was done with a centralised computer-generated procedure; patients were stratified by histological subtype (B-cell vs T-cell lymphoma) and donor match (HLA-identical vs non-identical). Neither investigators nor patients were masked to allocation. The primary endpoints were the incidence of acute graft-versus-host disease grade 24 in each treatment group and overall survival at 1 year in both groups combined. All analyses were done for the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00785330.

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#Shake4Mike: 'I wanted to be his rock in return'

He was still waiting to hear back from a job interview, so I assumed it was about that and I got really excited, she says. I tried to ring a few times, and eventually I got through over quite a patchy line. He said, 'I think Ive got leukaemia. When you hear those words, you know how serious it is. I just told him, 'Im going to get home as quickly as I can.

The news that followed was devastating. Mike, 29, was diagnosed with acute lymphoblastic leukaemia and is currently undergoing intense chemotherapy six times a week at Bristol Royal Infirmary. Such is the severity of his condition that doctors have said he needs a stem-cell transplant to save his life and time is running out.

As has been widely reported this week, his family, who live in Somerset, have only until the start of July, when his chemotherapy course ends, to find a suitable donor. Normally a third of people requiring the operation are able to find a sibling match. All of his three brothers have already been tested, but none has been successful.

He and his loved ones are now searching the Anthony Nolan stemcell donor register for a match with a stranger willing to help. The charity warns, however, that it can normally find a suitable donor for only around half the people who need a life-saving stem-cell transplant.

Kate, as a result, has taken matters into her own hands. This week, she launched a public campaign for people to sign up to the register, urging social media users to post silly videos of themselves shaking their faces from side to side something the couple used to film each other doing to promote the campaign she has called #Shake4Mike.

Her hope, of course, is that more signatories to the register will boost her fiancs chances of finding a donor and she has been inundated with responses. Some have been so funny theyve made me laugh out loud.

Indeed, in conversation, the Nottingham University graduate is strikingly upbeat and resilient. But optimism in the face of tragedy is a skill she has already been forced to master. In 2005, her 59-year-old father, David, died suddenly at the family home in Aylesbury, Buckinghamshire, after developing a blood clot following an operation on a hip he had broken skiing. He had just eaten his Sunday roast and walked on his crutches to the living room and died.

A few weeks later, her grandparents followed him. In 2008 her mother, Ali, invited her best friend, Simon Blackett, to move in to help support the family. Within two months, the 38-year-old suffered a fatal brain haemorrhage.

It was a year after this latest loss that the couple first met. Kate says her fianc has helped turn her life around and that, ever since she received that phone call in Burma, she has been determined to be his rock in return.

Still, the journey home was in itself enough to test her emotional strength. She remembers a horrendous 48-hour blur of buses and planes. Mum picked me up straight from Heathrow and drove me to the hospital. I thought when I saw her Id break down, but shes really strong and that helped so much. When I got to the hospital and saw him he looked pale, but other than that it was just a relief to be with him, says Kate.

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#Shake4Mike: 'I wanted to be his rock in return'