Children’s Hospital Los Angeles is announcing participation in the first-ever clinical trial using stem cells from umbilical cord blood to delay or even prevent heart failure in children born with a rare congenital heart defect that leaves them with half a heart.
“It is very exciting that Children’s Hospital Los Angeles has joined the HLHS consortium. It means that individuals with HLHS now have more options when it comes to participating in groundbreaking clinical trials and other research”
The Phase I study is part of a multi-center collaboration dedicated to employing innovative therapies to improve outcomes for children with hypoplastic left heart syndrome (HLHS), a congenital heart defect in which the left ventricle is severely underdeveloped. The HLHS Consortium, launched at the Mayo Clinic in Minnesota in 2017, involves four regional centers. CHLA, the only West Coast member, makes the initiative bicoastal.
“We’re proud to be part of this select group of institutions,” says Vaughn Starnes, MD, co-director of the Heart Institute at CHLA and chair, Department of Surgery, at the Keck School of Medicine of the University of Southern California. “As a leading center for medical and surgical treatments for HLHS, we want to be at the forefront of the next transformative therapy for treating this complex condition.”
In addition to the Mayo Clinic, other Consortium members include Children’s Hospital of Philadelphia and Minnesota Children’s Hospital.
“It is very exciting that Children’s Hospital Los Angeles has joined the HLHS consortium. It means that individuals with HLHS now have more options when it comes to participating in groundbreaking clinical trials and other research,” says Timothy Nelson, MD, PhD, director of the Mayo Clinic’s Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome.
In HLHS, the left ventricle of the heart can’t pump oxygen-rich blood from the lungs to the rest of the body. Without surgical intervention, HLHS is fatal. Children undergo a series of three surgeries in their first three years to make the right ventricle the heart’s main pumping chamber and improve blood flow.
This first-of-its-kind clinical trial combines pioneering surgical techniques with regenerative medicine. “This is one of the earliest efforts at harnessing the power of stem cell technology for the care of children with a serious cardiac disease,” says Ram Kumar Subramanyan, MD, PhD, a cardiothoracic surgeon who is heading the HLHS study in CHLA’s Heart Institute.
CHLA first performed HLHS surgery in 1992. In the decades since, doctors have found that as children with HLHS reach adolescence, their reconstructed hearts are deteriorating. For some, that means heart failure and the need for a heart transplant. “We are looking for novel approaches to this vexing problem,” says Starnes.
At the time of delivery, newborns enrolled in the study will have their umbilical cord blood collected and sent to the Mayo Clinic where the stem cells are removed. Within a few hours of birth, the baby arrives at CHLA and has the first HLHS surgery 2 to 5 days later.
The second open-heart surgery, the Glenn procedure, takes place at about six months of age, when the baby’s own stem cells are injected back into their heart. The hypothesis is that stem cells will stimulate the heart muscle to grow during the critical first year of life, when cardiac cells still have the ability to proliferate. At about three years of age, the child then has the third surgery, the Fontan procedure.
All children in the study will be followed long-term, as doctors look for signs that their hypothesis is working to produce a stronger heart for these at-risk children.
Together, the HLHS Consortium members hope to recruit about 20 children for the Phase I umbilical cord blood study. CHLA investigators already have enrolled several families.
Funding for CHLA’s participation in the Consortium has been provided in part by the Taglyan Family.
A consistent sleep schedule is key to unlocking healthy benefits such as skin that feels fresh and rejuvenated and a strong heart and immune system. A new study says that you can catch up on sleep on the weekend and undo some of the damage caused by lack of zzz’s Monday through Friday—like feeling like you’re drunk at work.
The findings were published in the Journal of Sleep Research, which analyzed the relationship between sleep and mortality rates; it examined data from more than 38,000 adults in Sweden who answered a medical survey in 1997 and then were tracked for 13 years through a national death register. According to the results, people younger than 65 who got five hours of sleep or less seven days a week had a 65 percent higher morality rate than people who got a healthy six or seven hours of sleep. (In case I hadn’t stressed this enough, sleep really is important!) But they also showed that people who got five hours of sleep a night during the week and then caught up on weekends by snoozing for eight hours or more a night experienced the same mortality rate as those who consistently slept six or seven hours nightly.
However, too much regular sleep (eight or more hours nightly) was linked to a 25 percent higher mortality rate than those who slept six or seven hours nightly—but that may be because oversleeping can be an indicator of health problems, as lead author of the study, Torbjörn Åkerstedt, PhD, a professor and director of Stress Research Institute, told The Guardian.
Although busy bees will be pleased to hear their hectic lifestyles won’t negatively impact their longevity (at least where zzz’s are concerned), you should know that the study is limited: Participants were only asked about their sleep habits once in 1997, and they self-reported them, which sacrifices accuracy. Still, Stuart Peirson PhD, associate Professor in the Nuffield Laboratory of Ophthalmology, said the results make sense, since the longer you are awake the more sleep you need—your “sleep debt” needs to be “paid off,” he told The Guardian.
Hopefully, additional research will find further evidence to support the ethos of work hard, sleep hard.
McMaster University researchers have found cord blood that has been stored through freezing for long periods of time has the potential to be used as a treatment for breast cancer.
The research comes as McMaster health scientists seek additional medical opportunities for frozen, or cryopreserved, cord blood currently in storage around the world, since this reservoir is most commonly used for stem cell transplants.
The results were recently published in The Journal of Immunotherapy.
“It is important to explore ways we can utilize the vast quantities of long-term cryopreserved cord blood and understand its full potential as a therapeutic product,” said Ali Ashkar, corresponding author and professor of the Department of Pathology and Molecular Medicine with McMaster’s Michael G. DeGroote School of Medicine.
Comparing 10.5 and 2.5 year-old cryopreserved blood to fresh cord blood, researchers derived what are called ‘natural killer’ cells. This is a type of white blood cell that is important in eliminating tumour and virus-infected cells.
Based on experimentation conducted outside of the human body, known as ex vivo, researchers measured the ability to generate vast quantities of activated natural killer cells and their effectiveness in destroying breast cancer cells.
The results showed long-term cryopreservation had no negative effect on the expansion potential or function of the activated cord blood natural killer cells. The research also indicated these cells had a particular effectiveness in attacking primary breast cancer cells.
“We demonstrated it is possible to obtain an exponential amount of natural killer cells from older cryopreserved cord blood,” said Ashkar. “This makes it a viable source of cells for the advancing field of natural killer cell cancer immunotherapy, especially as it applies to breast cancer.”
There are currently more than 600,000 units of cord blood stored globally, with that number expected to increase as storage technology develops. To date, there have been approximately 30,000 cord blood transplants performed.
“Cord blood can be stored at birth so that in the event it is needed, it can later be used to help treat the child,” said Tina Nham, lead author of the study and a second-year McMaster medical student. “This study demonstrates that instead of discarding cord blood samples when the child is grown, cord blood can be cryopreserved and later harnessed as an immunotherapy with the potential to treat a variety of illnesses including breast cancer.”
“It is unclear what happens to publicly or privately-banked cord blood samples that are stored for extensive periods of time,” said Ashkar. “We suggest the ability to store cord blood samples that maintain functionality after decades of cryopreservation, as this raises the possibility of housing vast, diverse and long-lasting donor libraries where readily available sources of therapeutic natural killer cells can be harvested.”
Additional authors on the study came from McMaster University’s Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre and the Nationwide Children’s Hospital in Columbus, Ohio.
The original article can be viewed here.
Another reason to save your baby’s cord blood stem cells today.
Stroke is a major cause of death and long-term disability, affecting one in six people worldwide. The only currently available approved pharmacological treatment for ischemic stroke is tissue plasminogen activator; however, relatively few patients are eligible for this therapy.
We hypothesized that intravenous (IV) infusion of banked unrelated allogeneic umbilical cord blood (UCB) would improve functional outcomes in patients with ischemic stroke. To investigate this, we conducted a phase 1 open-label trial to assess the safety and feasibility of a single IV infusion of non-human leukocyte antigen (HLA) matched, ABO matched, unrelated allogeneic UCB into adult stroke patients. Ten participants with acute middle cerebral artery ischemic stroke were enrolled. UCB units were matched for blood group antigens and race but not HLA, and infused 3-9 days post-stroke. The adverse event (AE) profile over a 12 month postinfusion period indicated that the treatment was well-tolerated in these stroke patients, with no serious AEs directly related to the study product.
Study participants were also assessed using neurological and functional evaluations, including the modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS). At 3 months post-treatment, all participants had improved by at least one grade in mRS (mean 2.8 ± 0.9) and by at least 4 points in NIHSS (mean 5.9 ± 1.4), relative to baseline.
Together, these data suggest that a single i.v. dose of allogeneic non-HLA matched human UCB cells is safe in adults with ischemic stroke, and support the conduct of a randomized, placebo-controlled phase 2 study. Stem Cells Translational Medicine 2018.
The original article can be viewed here.
A new study in Royal Society Open Science found that moods spread across friend groups like a “social contagion.”
Researchers surveyed more than 2,000 middle and high school students in the USA over a period of six months to a year.
As part of the check-ins, depression screenings were administered to identify any common thread among the moods, feelings, and levels of happiness in the friends.
The study found evidence that moods – happy or sad, spreading across friend groups like wild fire. (But though low moods were found to be socially catching, clinical depression was not).
So while misery may well love company – being around an upbeat person will make your outlook sunnier.
An infusion of cells from a child’s own umbilical cord blood appears to improve brain connectivity and motor function in children with spastic cerebral palsy.
The results of the randomized clinical trial were recently published by Stem Cells Translational Medicine.
The placebo-controlled, phase two trial included 63 children with varied types and severities of spastic cerebral palsy, a condition usually caused by brain damage before or at birth.
Children who received one intravenous dose of at least 25 million stem cells per kilogram of their body weight saw improvements in motor function a year later.
The improvements were greater than those typically observed for children of similar age and condition, and exceeded the gains made by children who received a lower dose of cells or a placebo.
“We are encouraged by the results of this study, which shows that appropriately dosed infusions of cord blood cells can help lessen symptoms in children with cerebral palsy,” said senior author Joanne Kurtzberg, M.D., director of Duke’s Pediatric Blood and Marrow Transplant Program and the Robertson Clinical and Translational Therapy Program.
“We still have a lot to learn about this therapy so that it can be optimized and accessible to more children with cerebral palsy,” said Kurtzberg, who is also director of the Carolinas Cord Blood Bank at Duke.
“Previous research has indicated it’s safe for children with cerebral palsy to receive an infusion of their own cord blood,” Kurtzberg said. “Now that we have identified a dosing threshold, we are planning additional studies testing the benefits of multiple doses of cells, as well as the use of donor cells for patients whose own cord blood was not banked.”
Kurtzberg has been a pioneer in testing the therapeutic potential of umbilical cord blood, which has been found to be a rich source of blood stem cells to treat cancers, neurological disorders and genetic diseases. Cord blood also contains other therapeutic cells that researchers believe could influence the formation of new neural connections in children with cerebral palsy.
In the cerebral palsy trial, Kurtzberg and colleagues tested doses from 10 million cells per kilogram of body weight up to 50 million cells per kilogram, based on the amount and quality of the cord blood each child had in storage. Among the tools used to evaluate the children’s progress were MRI to measure brain connectivity and the Gross Motor Function Measure (GMFM-66), a standardized analysis of a child’s ability to crawl, roll, kneel, and complete other movements based on age and development.
Children who have cerebral palsy are expected to gain motor function as they grow and develop and receive traditional therapies, including occupational and physical therapy, said Jessica Sun, M.D., a pediatric hematologist-oncologist at Duke and lead author of the paper. The GMFM-66 attempts to account for this expected growth based on age and the severity of the cerebral palsy, she said, and most participants improved when retested on the GMFM-66 a year after receiving an infusion, even those who received a placebo.
However, the improvements for children who received doses of at least 25 million cells per kilogram of body weight progressed beyond their expected increases when they were tested a year after infusion.
“For each child, the improvements are different and could be subtle, but sometimes even a seemingly small difference is significant,” Sun said. “For example, a child’s ability to turn their hand from facing down to facing up can change their ability to hold or grasp something, which can make a big difference in their everyday life.”
The study had some limitations, including the requirement that participants have cord blood in storage and be able to travel to Duke, both of which required financial means, the authors said. Being from well-resourced families, most participants were also receiving frequent physical and occupational therapy, Sun said, and those advantages could have influenced the results.
“We are hopeful that cord blood and cell therapy may have a role in treating children with cerebral palsy and brain injury and are encouraged to continue this promising research,” Sun said.
When he was born at Mount Sinai Hospital in Toronto, Jack was not breathing and was non-responsive.
Doctors whisked him away from his mother and started efforts to resuscitate him. They managed to save his life but soon had to deliver some bad news to his parents, Stephen Pankratz and Kim Kucher.
Their son had Hypoxic Ischemic Encephalopathy (HIE), brain damage caused by lack of oxygen and compounded by low blood flow to vital organs. Jack would likely suffer extensive cognitive and physical problems.
But at only 12 days old Jack was re infused with his own stem cells – the youngest person ever to undergo stem cell therapy in Canada and the first person in the country to be treated for HIE with stem cells.
Doctors believe he may turn out to be the first of many.
Two years later, Jack is thriving. He has cerebral palsy and faces many challenges, but his development has exceeded doctor’s expectations. His mother attributes his progress to the re-infusion.
Dr. Joanne Kurtzberg, a researcher at Duke University in Durham, N.C, has been leading clinical trials to determine whether cord blood can help to repair the brain. Research results published by Duke University indicate that early transfusion of cord stem cells is effective.
Jack’s parents discovered Kurtzberg’s findings while doing research on HIE in the days following their son’s birth. They brought them to the attention of his neonatologist, Dr Karen Pape.
“She was open to hearing what we had to say and she read the research findings that we had given her,” says Pankratz. “She came to the same conclusion as us — that the potential benefits of a stem cell transplant outweighed the risks.
In scientific and medical circles, many stem cell experts are predicting the dawn of a new era in the treatment of HIE, autism and other brain disorders – with cord blood stem cells treatment playing a key role.
Umbilical cord blood could provide a lifesaving treatment for heart failure patients, a new study has found.
The report from the American Heart Association, published in September 2017, revealed that stem cells from cord blood boosted patients’ heart function when administered.
Experts are hopeful that the study could improve the lives of the 37 million people worldwide who live with heart failure, as current treatments involve invasive procedures and medications that take a toll on patients’ bodies.
The study involved 30 heart failure patients aged 18 to 75. While some were treated with umbilical cord blood, others got a placebo drug.
The heart muscles of those who were injected with umbilical cord cells saw ‘significant’ improvement during the year following the trial. This included an improved ability to pump blood and function at a higher level.
The effects resulted in an improved quality of life for the patients who had received the cells, the study said.
Study author Dr Jorge Bartolucci said that the treatment could transform the way doctors think about heart failure treatments because current options for treating the fatal disease are complicated and ineffective.
‘Standard drug-based regimens can be suboptimal in controlling heart failure, and patients often have to progress to more invasive therapies such as mechanical ventricular assist devices and heart transplantation,’ Dr Bartolucci said.
Another researcher who worked on the study, Dr Fernando Figueroa, echoed the excitement over the study’s potential.
‘We are encouraged by our findings because they could pave the way to a non-invasive, promising new therapy for a group of patients who face grim odds,’ he said.
The study pointed out that, even though recent medical advances have improved these odds, half of the people who are diagnosed with heart failure die within five years of their diagnosis.
The American Heart Association journal, Circulation Research published the results of the study.
Dementia patients have been offered hope that their memory could be repaired after scientists showed that cord blood restores brain function.
Researchers at Stanford University School of Medicine in the US discovered that cord blood contains an important protein which vanishes as humans get older. It is believed the protein encourages neuroplasticity in the brain, allowing neurons to adapt and communicate more effectively.
When human cord blood was injected into elderly mice they performed far better in learning and memory tests and even started nesting again, gathering up cotton wads to make beds, an instinctive behaviour that is largely forgotten in old age.
Alzheimer’s Society head of research Dr James Pickett said: “Everyone experiences some decline in memory as they get older. The possibility that this process can be reversed by an infusion of young blood sounds like the stuff of science fiction, but this is what the study is beginning to show.”
“This study finds that a factor in human umbilical cord blood can enter the brain and restore some of the processes that are essential for forming new memories.”
The researchers think the cord blood repairs the hippocampus, a part of the brain which in both mice and humans is critical for converting experiences into long-term memories.
In particular, the hippocampus is essential for helping people remember spatial information, such as how to find your way back to your car or information about autobiographical events, such as what you ate for breakfast.
The new study marks the first demonstration that human blood can aid older mice’s memory and learning, which the authors say increases the likelihood that it could have a similar beneficial effect in people.
“Neuroscientists have ignored it and are still ignoring it, but to me it’s remarkable that something in your blood can influence the way you think,” said the study’s senior author, Dr Tony Wyss-Coray, PhD, professor of neurology and neurological sciences at Stanford.
“For largely unknown reasons, the hippocampus is especially vulnerable to normal ageing. With advancing age, the hippocampus degenerates, loses nerve cells and shrinks. Hippocampal deterioration is also an early manifestation of Alzheimer’s disease.
“Our results argue that systemic factors which present early in life may be beneficial for revitalisation of aged tissue and that (the protein) represents such a restorative factor for the aged hippocampus.”
The Stanford team had already proved that young blood can reverse some of the signs of ageing in mice but have never shown it could restore learning and memory.
For the new experiment, they injected either cord blood plasma, or the blood from people aged between 19 and 24, or 61 and 82.
When the older mice received human umbilical-cord blood plasma every fourth day for two weeks, their memory, learning and hippocampal function improved notably, as well as their ability to navigate through a complex maze. Plasma from older people, on the other hand, was no help at all, while young-adult plasma only induced an intermediate effect.
After realising that something in the umbilical cord blood was making the old brains act younger, the scientists set about trying to work out what it was, and discovered a protein called TIMP2
Injecting TIMP2 by itself into elderly mice largely duplicated the beneficial effects of umbilical-cord blood.
“TIMP2’s effects in the brain have been studied a little, but not much and not in ageing,” added study author Dr Joseph Castellano, an instructor of neurology and neurological sciences at Stanford.
“In our study, it mimicked the memory and learning effects we were getting with cord plasma. And it appeared to do that by improving hippocampal function.
“In the current study, we have focused on age-related cognitive decline, but future studies will probe the extent to which TIMP2 might be beneficial in the context of more severe synaptic and neuronal dysfunction, for example, in Alzheimer’s disease.”
Experts in Britain said the research was interesting but called for more work on whether TIMP2 could also influence the brain activity in humans.
The study was published in the journal Nature.