Stem Cell Clinic

Patients’ plasma, stem cells help knee problems – The Columbus Dispatch

By adminJuly 31, 2017Stem Cell Medical Center

JoAnne Viviano The Columbus Dispatch @JoAnneViviano

Dennis Matko was headed for a knee replacement when he discovered a new therapy that would instead inject his own stem cells and plasma into the joint to help prevent degradation.

The 69-year-old Clintonville resident said he had been pretty active in his 50s, leading to problems with the right knee. He eventually had his meniscus removed. He had been through physical therapy, cortisone shots and gel injections, but the pain persisted.

The therapy, he said, was a no-brainer. He was sold because the procedure involved putting his own fluids into his body with no foreign objects and no drugs.

Dr. Joe Ruane, the orthopedic doctor who treated Matko, introduced the therapy at OhioHealth, but there are a number of places using the therapy around the state and country.

It's used to treat people with osteoarthritis, the type of arthritis caused by wear and tear.

Ruane said that the need for total knee replacements in the U.S. is expected to climb by 600 percent in the next 20 years, and there is concern that there might not be enough surgeons to perform the procedures.

We need an alternative, and patients are looking for alternatives, and given the choice between a knee replacement and an injection, many patients would choose an injection, he said.

The treatment involved removing Matkos bone marrow from the back of his pelvic bone, a process done in the office under general anesthesia. The marrow was then processed to form a concentrate of stem cells and other growth factors.

Matko also had blood drawn to create platelet-rich plasma, which acts as a signaling system to get the stem cells to respond.

Ruane injected both components into the knee, delivering more than 100 stimulating and growth factors to the joint.

Ruane said the process inhibits irritating chemicals that contribute to inflammation, decreases the activity of enzymes that break down cartilage, and helps the knee to make some of its own joint fluid again.

And, to a small degree, it does help regrow some of the tissue in the knee that has been destroyed by the arthritis, Ruane said.

The procedures are most effective in young patients with early arthritis, said Dr. Adolph Lombardi of Joint Implant Surgeons in New Albany, where stem-cell and platelet-rich plasma injections are offered as separate therapies. It won't help with bone-on-bone disease, he said.

While other injections might offer short-term pain relief, platelet-rich plasma has been shown to offer a full year of relief, said Lombardi, who works with the Mount Carmel Health System. The idea is that bone-marrow stem cells, when injected into a hip or knee, can differentiate into cartilage cells and help with regeneration.

"All of this is very new but it seems to be extremely promising," Lombardi said. "This is using their own bodies' healing potential to maintain cartilage and relieve pain."

Dr. Michael Baria performs the procedure at Wexner Medical Center at Ohio State University, where the bone-marrow and platelet-rich plasma injections also are offered as separate treatments. He agreed that the hope with the bone-marrow injections is that the stem cells turn into cartilage cells, improving or halting the osteoarthritis disease.

But in his experience, the treatment is helpful for patients with advanced disease.

"The most common patient we see for this is going to be in late-stage arthritis, so kind of at the end of their rope," Baria said. "Platelet-rich plasma is usually not as good for bone-on-bone arthritis. Bone marrow doesnt seem to be limited by bone on bone."

The body has trouble healing arthritis because cartilage doesnt get enough blood supply, Ruane said. Injecting the stem cells boosts the bodys own process.

While platelet-rich plasma has been shown to decrease inflammation, stem-cell use is newer and has yet to be proven effective, Baria noted.

OhioHealth andJoint Implant Surgeons are currently in the midst of controlled randomized trials, hoping to prove the effectiveness of the procedures and obtain approval from the U.S. Food and Drug Administration.

Unless that happens, the procedure will be considered experimental, and insurance doesnt cover costs. Matko paid $2,800 for the injections at OhioHealth.

Before the treatment, Matko was having trouble with mundane things like going up and down stairs and with other activities, such as taking hikes or walks with his wife or working out. A retired police officer, he now works as a business consultant and spends a lot of time on his feet, so he was looking for better mobility there as well.

Matko said the injections have helped his knee, which is getting progressively better over time. He said hes been able to increase his activity, getting back to the gym and taking hikes and walks. He has minimal pain climbing stairs and hes more comfortable in his work.

Im not saying its all better but its much better, Matko said. Its headed in the right direction.

He realizes the treatment is not a cure.

Im not looking for a miracle, he said. I just want to forestall problems as long as possible.

jviviano@dispatch.com

@JoAnneViviano

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Patients' plasma, stem cells help knee problems - The Columbus Dispatch

Glial cells botch wiring in childhood schizophrenia – Futurity: Research News

By adminJuly 31, 2017Stem Cell Medical Center

Malfunctioning glial cells that keep nerve cells from forming working communication networks may be the basis of the wiring problems in the brains of people with schizophrenia, new research suggests.

The inability of these cells to do their jobappears to be a primary contributor to the disease.

When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia into mice, the animals nerve cell networks did not mature properly and the mice exhibited the same antisocial and anxious behaviors seen in people with the disease.

The findings of this study argue that glial cell dysfunction may be the basis of childhood-onset schizophrenia, says neurologist Steve Goldman, co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and lead author of the study.

The inability of these cells to do their job, which is to help nerve cells build and maintain healthy and effective communication networks, appears to be a primary contributor to the disease.

Glia are an important family of support cells found in the brain and play a critical role in the development and maintenance of the brains complex interconnected network of neurons. Glia includes two major types: astrocytes and oligodendrocytes.

Astrocytes are the brains principal support cells, while oligodendrocytes are responsible for producing myelin, the fatty tissue that, like the insulation on electrical wires, wraps the axons that connect different nerve cells. The source of both these cells is another cell type called the glial progenitor cell (GPC).

Astrocytes perform several functions in the brain. During development, astrocytes colonize areas of the brain and establish domains in which these cells help direct and organize the network of connections between nerve cells.

Individual astrocytes also send out hundreds of long fibers that interact with synapsesthe junction where one neurons axon meets anothers dendrite. The astrocytes help facilitate the communication between neurons at the synapses by regulating the flow of glutamate and potassium, which enable neurons to fire when they are communicating with each other.

In the new study, the researchers obtained skin cells from individuals with childhood-onset schizophrenia and reprogrammed the cells to create induced pluripotent stem cells (iPSC) which, like embryonic stem cells, are capable of giving rise to any cell type found in the body. Next, the team manipulated the iPSCs to create human GPCs.

The human GPCs were then transplanted into the brains of neonatal mice. These cells out-competed the animals own native glia, resulting in mice with brains comprised of animal neurons and human GPCs, oligodendrocytes, and astrocytes.

The researchers observed that human glial cells derived from schizophrenic patients were highly dysfunctional. The development of oligodendrocytes was delayed and the cells did not create enough myelin-producing cells, meaning signal transmission between the neurons was impaired.

The development of astrocytes was similarly tardy so that the cells were not present when needed and were thus ineffective in guiding the formation of connections between neurons. The astrocytes also did not mature properly, resulting in misshapen cells that could not fully support the signaling functions of the neurons around them.

The astrocytes didnt fully mature and their fibers did not fill out their normal domains, meaning that while they provided control to some synapses, others had no coverage, says Martha Windrem, also with the Center for Translational Neuromedicine and first author of the study. As a result, the neural networks in the animals became desynchronized and uncoordinated.

The researchers also subjected the mice to a series of behavioral tests. They observed that the mice with human glial cells from individuals diagnosed with schizophrenia were more fearful, anxious, anti-social, and had a variety of cognitive deficits compared to mice transplanted with human glial cells obtained from healthy people.

The studys authors point out that the new research provides scientists with a foundation to explore new treatments for the disease. Because schizophrenia is a unique to humans, until now scientists have been limited in their ability to study the disease. The new animal model developed the by the researchers can be used to accelerate the process of testing drugs and other therapies in schizophrenia.

The study also identifies a number of glial gene expression flaws that appear to create chemical imbalances that disrupt communication between neurons. These abnormalities could represent targets for new therapies.

Additional coauthors of the study are from the University of Rochester, the University of Copenhagen, George Washington University, Johns Hopkins University, and Case Western University.

The study appears in the journal Cell. Funding from National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the G. Harold and Leila Y. Mathers Charitable Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the Novo Nordisk and Lundbeck Foundations supported the research.

Source: University of Rochester

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Glial cells botch wiring in childhood schizophrenia - Futurity: Research News

Dozens of US clinics sell unproven stem cell therapies for heart failure – Reuters

By adminJuly 30, 2017Stem Cell Medicine

(Reuters Health) - Stem cell therapy isnt approved to treat heart failure in the U.S., but dozens of clinics nationwide advertise the treatments anyway, often charging thousands of dollars for procedures that may not be safe or effective, a new study suggests.

Researchers found 61 centers offering stem cell therapies for heart failure as of last year in the U.S. alone, including five that claimed to have performed more than 100 procedures. Only nine centers required copies of patients medical records and just one facility said it had a board certified cardiologist on staff.

We simply do not know anything about the quality of the treatment delivered at these centers, said senior study author Dr. Paul Hauptman director of heart failure at Saint Louis University Hospital.

These centers are not regulated in any way, Hauptman said by email.

Almost 6 million Americans have heart failure, and its one of the most common reasons older adults go to the hospital, according to the American Heart Association.

It happens when the heart muscle is too weak to effectively pump enough blood through the body. Symptoms can include fatigue, weight gain from fluid retention, shortness of breath and coughing or wheezing. Medications can help strengthen the heart and minimize fluid buildup in the body.

While some experimental stem cell therapies for heart failure are currently being tested in late-stage human trials, none have won approval from the U.S. Food and Drug Administration.

In theory, after a transplant, stem cells could permanently become part of the diseased heart and either help grow new healthy heart tissue or tell existing cells to work better, said Paul Knoepfler, a cell biology researcher at the University of California Davis School of Medicine in Sacramento who wasnt involved in the study.

Its also possible stem cells could temporarily visit the heart and stimulate a positive response in cells already there, he said.

Even though theres no conclusive proof yet that any stem cell treatments are safe and effective for heart failure, centers contacted for the study charge an average of $7,694 for each treatment using patients own stem cells and $6,038 for each procedure with donor stem cells.

In one instance, though, a clinic staff member said, If you have a million dollars to spend we will set you up with weekly infusions.

Hauptmans team had used a standard script when contacting each center, asking about the stem cell treatment itself, medical exams before and afterward and pricing.

Among the other responses they received from clinic staff were remarks such as, If you know anyone that can start an IV, a neighbor that is a nurse for example, we can send you the stem cells and that person can administer them to you and We hope you don't believe your doctor when they tell you there is nothing they can do, you were smart to call us.

None of the sites in the study discussed what methods they used to isolate or identify stem cells, though most claimed to use patients cells and 24 said they got cells from fat tissue.

Most centers claimed to deliver cells intravenously, researchers report in JAMA Internal Medicine.

This approach has been associated with complications such as stroke, in which infused cells block blood vessels in the brain, said Douglas Sipp, a researcher at RIKEN Center for Developmental Biology in Kobe, Japan, who wasnt involved in the study.

The biggest risk is that patients will waste their money, time and hopes on an unnecessary and useless invasive procedure, Sipp said by email.

If any stem cell treatment did ultimately prove safe and effective enough to win FDA approval, it would likely offer a significant improvement over the limited treatment options currently available, said Leigh Turner, a researcher at the University of Minnesota Center for Bioethics who wasnt involved in the study.

But its impossible to say what patients would get at unregulated clinics offering unapproved stem cell therapies, Turner said by email. In at least two cases unrelated to the current study, patients died after getting stem cell procedures at a clinic in Florida, and in another case at a different Florida clinic, a woman went blind, Turner noted.

Clinics marketing stem cell treatments to patients suffering from heart failure might be administering anything from slurries of mixed cells, some of which might be stem cells, to nothing more than cellular debris, Turner said. Often one can only speculate.

SOURCE: bit.ly/2uQve40 JAMA Internal Medicine, online July 24, 2017.

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Dozens of US clinics sell unproven stem cell therapies for heart failure - Reuters

The Big Deal About Stem Cell Therapies and Regenerative Medicine – PR Newswire UK (press release)

By adminJuly 30, 2017Stem Cell Medicine

However, when looking at this great promise in terms of return on investment, let us be completely honest, most early stage stem cell investors have lost their shirts. We are now more than twenty years removed from the earliest commercial stem cell companies that were founded in the late 1980's, went public in the late 1990's and who were once seen as an exciting investment opportunity, but ended up being a huge disappointment.

So, should investors still be interested in regenerative medicine? After all, stem cells have largely produced failures and unregulated stem cell clinics marketing unproven therapies are taking over. The answer is a resounding yes, but the dot-com like era of regenerative medicine, which led investors to pour money into anything and anyone marketing a cell therapy is over. Investors will need to look at companies solving issues with stem cells or those taking a completely new approach.

One company that is looking to address many of the issues with stem cell therapies, as well as developing another approach to regenerative medicine is Endonovo Therapeutics, Inc. (OTCQB: ENDV). On the stem cell front, ENDV is using its Time Varying Electromagnetic Fields (TVEMF) technology, originally developed at the National Aeronautics and Space Administration (NASA) to expand and activate stem cells to produce more biologically potent cell therapies. However, more importantly, ENDV is developing a non-invasive medical device that would render many of the cell therapies currently under development obsolete. These devices, called Electroceuticals, harness the electrical signals that our cells and nerves use to control the immune and regenerative response to treat inflammatory and degenerative diseases. ENDV is developing this exciting technology for treating and preventing heart failure following a heart attack, to treat chronic kidney disease, peripheral artery disease and non-alcoholic steatohepatitis (NASH).

Another small biotech company like ENDV working on electric treatments for diseases is Pulse Biosciences (NASDAQ: PLSE), whose Nano-Pulse Stimulation (NPS) technology uses nano second electric pulses to illicit an immune response for the treatment of cancer. PLSE recently announced the treatment of its first patient in a study to evaluate the safety and efficacy of its novel NPS technology for seborrheic keratosis (SK) lesions. SK is one of the most common types of skin lesions, affecting more than 80 million patients in the United States. Additionally, PLSE announced that it will host its quarterly investor conference call on July 27, 2017, at 1:30 p.m. PDT / 4:30 p.m. EDT. The company will provide an update on the clinical advancement of the PulseTx[TM] System, including progress of the clinical study evaluating NPS for the treatment of seborrheic keratosis (SK), as well as the status of the 510(k) submission from earlier this year.

Another company seeking to address past pitfalls of stem cell therapies is Pluristem Therapeutics, Inc. (NASDAQ: PSTI) is a developer of placenta-based cell therapy product candidates for the treatment of multiple ischemic, inflammatory and hematologic conditions. Pluristem's products include PLX-PAD and PLX R18. The Company's PLX cells are adherent stromal cells (ASCs) that are expanded using a three dimensional (3D) process. The system utilizes a synthetic scaffold to create an artificial 3D environment where placental-derived stromal cells can grow. This process allows the cells to be expanded rapidly while remaining healthy and potent cells that can secrete therapeutic biomolecules. The Company's PLX products are administered using a standard needle and syringe. PSTI recently announced that Austria's regulatory health agency, the Austrian Agency for Health and Food Safety (AGES), had cleared Pluristem to begin enrollment in Austria for its pivotal Phase III trial of PLX-PAD cells to treat critical limb ischemia.

In other stem cell news:

Cytori Therapeutics, Inc. (NASDAQ: CYTX) recently announced that its STAR study assessing its Habeo Cell Therapy for the treatment of Scleroderma had failed to meet its primary endpoint at week 24 nor any of its secondary endpoints at week 24 or week 48. On the other hand, CYTX stated that there were 'clinically meaningful' improvements in both the primary and secondary endpoints of both hand function and scleroderma-associated functional disability compared to placebo in a subgroup of patients with diffuse cutaneous scleroderma, a more severe form of the disease. The company has stated that it will continue it analysis of the data before determining its next steps.

Capricor Therapeutics, Inc. (NASDAQ: CAPR) a biotechnology company developing biological therapies for Duchenne muscular dystrophy and other rare diseases, following news that Janssen Biotech, Inc. had decided not to exercise its option to exclusively license Capricor's lead candidate CAP-1002 for the development and commercialization in the field of cardiology, announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation to CAP-1002, Capricor's development candidate for the treatment of Duchenne muscular dystrophy, a debilitating genetic disorder characterized by progressive weakness and chronic inflammation of skeletal, heart, and respiratory muscles. The Rare Pediatric Disease Designation, as well as the Orphan Drug Designation previously granted to CAP-1002 by the FDA, covers the broad treatment of DMD. Upon receiving market approval for CAP-1002 by the FDA, Capricor would be eligible to receive a Priority Review Voucher.

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The Big Deal About Stem Cell Therapies and Regenerative Medicine - PR Newswire UK (press release)

Dozens of US clinics sell unproven stem cell therapies for heart failure – Fox News

By adminJuly 30, 2017Stem Cell Clinics

Stem cell therapy isn't approved to treat heart failure in the U.S., but dozens of clinics nationwide advertise the treatments anyway, often charging thousands of dollars for procedures that may not be safe or effective, a new study suggests.

Researchers found 61 centers offering stem cell therapies for heart failure as of last year in the U.S. alone, including five that claimed to have performed more than 100 procedures. Only nine centers required copies of patients' medical records and just one facility said it had a board certified cardiologist on staff.

NEUROLOGIST BACKS FAMILY'S FIGHT TO OVERTURN TEEN'S DEATH CERTIFICATE

"We simply do not know anything about the quality of the treatment delivered at these centers," said senior study author Dr. Paul Hauptman director of heart failure at Saint Louis University Hospital.

"These centers are not regulated in any way," Hauptman said by email.

Almost 6 million Americans have heart failure, and it's one of the most common reasons older adults go to the hospital, according to the American Heart Association.

While some experimental stem cell therapies for heart failure are currently being tested in late-stage human trials, none have won approval from the U.S. Food and Drug Administration.

CTE FOUND IN BRAINS OF 110 OUT OF 111 DECEASED NFLERS

It's also possible stem cells could temporarily visit the heart and stimulate a positive response in cells already there, he said.

Even though there's no conclusive proof yet that any stem cell treatments are safe and effective for heart failure, centers contacted for the study charge an average of $7,694 for each treatment using patient's own stem cells and $6,038 for each procedure with donor stem cells.

In one instance, though, a clinic staff member said, "If you have a million dollars to spend we will set you up with weekly infusions."

Hauptman's team had used a standard script when contacting each center, asking about the stem cell treatment itself, medical exams before and afterward and pricing.

Among the other responses they received from clinic staff were remarks such as, "If you know anyone that can start an IV, a neighbor that is a nurse for example, we can send you the stem cells and that person can administer them to you" and "We hope you don't believe your doctor when they tell you there is nothing they can do, you were smart to call us."

None of the sites in the study discussed what methods they used to isolate or identify stem cells, though most claimed to use patients' cells and 24 said they got cells from fat tissue.

Most centers claimed to deliver cells intravenously, researchers report in JAMA Internal Medicine.

"This approach has been associated with complications such as stroke, in which infused cells block blood vessels in the brain," said Douglas Sipp, a researcher at RIKEN Center for Developmental Biology in Kobe, Japan, who wasn't involved in the study.

"The biggest risk is that patients will waste their money, time and hopes on an unnecessary and useless invasive procedure," Sipp said by email.

DENTIST FACES CHARGES AFTER 4-YEAR-OLD SUFFERS BRAIN DAMAGE

But it's impossible to say what patients would get at unregulated clinics offering unapproved stem cell therapies, Turner said by email. In at least two cases unrelated to the current study, patients died after getting stem cell procedures at a clinic in Florida, and in another case at a different Florida clinic, a woman went blind, Turner noted.

"Clinics marketing stem cell treatments to patients suffering from heart failure might be administering anything from slurries of mixed cells, some of which might be stem cells, to nothing more than cellular debris," Turner said. "Often one can only speculate."

Link:
Dozens of US clinics sell unproven stem cell therapies for heart failure - Fox News

Stem cells in brain located by scientists could help reverse ageing process – The Independent

By adminJuly 30, 2017Adult Stem Cells

Scientists have identified a pea-sized part of the brain they say may hold the key to extending human lifespans.

Researchers found it was possible to slow and even reverse various aspects of ageing throughout the body by replenishing adult stem cells that control how quickly the body grows old.

The small bundle of neurons that appears to keep a tight rein on ageing is called the hypothalamus and is located at the base of the brain.

Dongsheng Cai, from the Albert Einstein College of Medicine in New York, led the new study in which tests were carried out on lab mice to pinpoint this area.

The research, published in the journal Nature, showed that as the number of these cells declines naturally over time, or if their function is disrupted, the bodys organs and metabolic processes age faster and death occurs earlier.

Our research shows that the number of hypothalamic neural stem cells naturally declines over the life of the animal, and this decline accelerates ageing, said Professor Cai. But we also found that the effects of this loss are not irreversible.

Ageing could be held back by replenishing these stem cells or the molecules they produce, he added.

The scientists believe that humans are likely to respond to the influence of hypothalamus stem cells in just the same way as the mice.

Brain activity appears to continue after people are dead, according to a study

The hypothalamus acts like a computers central processing unit (CPU), regulating a wide range of biological functions in the body and linking nerves and hormones.

One of its most important jobs is to maintain homeostasis keeping different parts of the body working in a constantly stable, balanced way.

Among the many body functions it influences are temperature control, appetite, blood pressure, heart rate, sleep cycles, sex drive, and digestion. It operates via a complex array of hormones.

The crucial hypothalamus stem cells are mother cells that mature to produce new neurons.

Professor Cais team of researchers looked at what happened to the cells as healthy mice got older.

They found that the number of hypothalamus stem cells began to diminish when the animals reached about 10 months, several months before the usual signs of ageing normally start to appear. Mice in captivity live a maximum of only about two to three years.

By old age about two years of age in mice most of those cells were gone, said Professor Cai. When the stem cells in middle aged mice were selectively disrupted artificially, it led to greatly accelerated ageing, he said.

The professor added: Those mice with disrupted stem cells died earlier than normal.

The next step was to inject hypothalamus stem cells into the brains of mice whose own supply of the cells had been destroyed, as well as normal old mice.

In both groups of animals, various measurements including tissue analysis and assessments of muscle endurance, coordination, social behaviour and mental abilityshowed that ageing was either slowed or reversed.

The anti-ageing effects were traced to molecules called microRNAs (miRNAs) released by the stem cells.

These small snippets of genetic material play a key role in regulating gene activity. By pairing up with messenger RNA molecules, which carry genetic code instructions to protein-building machinery in cells, they can effectively switch off certain genes.

When miRNA was extracted from hypothalamus stem cells and injected into the cerebrospinal fluid of mice, ageing was once again significantly slowed.

As a first step towards new anti-ageing treatments, the scientists are now trying to identify specific populations of anti-ageing microRNAs and possibly other secretions from hypothalamus stem cells that may play a role.

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Stem cells in brain located by scientists could help reverse ageing process - The Independent

Only as Old as the Brain’s Stem Cells Feel – Genetic Engineering & Biotechnology News

By adminJuly 30, 2017Adult Stem Cells

What the brain tells the body can accelerate aging and shorten lifespan. That much is already clear from recent studies on neuroendocrine interactions between the central nervous system and the periphery. These studies have even identified a brain region known to regulate growth, development, reproduction, and metabolismthe hypothalamusas a particularly important communications hub. Yet this brain regions cell-level contributions to aging regulation have been unclear.

A new study has listened to the hypothalamus more closely in hopes of picking up cell-level chatter that could influence aging speed. This study, which was completed by scientists based at Albert Einstein College of Medicine, tuned into a tiny population of adult stem cells. Already known to be responsible for forming new brain neurons, these stem cells, the scientists found, also regulate aging speed, partly through the release of exosomal microRNAs (miRNAs).

"Our research shows that the number of hypothalamic neural stem cells naturally declines over the life of the animal, and this decline accelerates aging," said the studys leader, Dongsheng Cai, M.D., Ph.D., a professor of molecular pharmacology at Einstein. "But we also found that the effects of this loss are not irreversible."

Details of the study appeared July 26 in the journal Nature, in an article entitled Hypothalamic Stem Cells Control Ageing Speed Partly through Exosomal miRNAs. The article describes how the scientists worked with mouse models in which hypothalamic stem/progenitor cells were evaluated.

Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan, wrote the articles authors. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment.

The researchers first looked at the fate of those cells as healthy mice got older. The number of hypothalamic stem cells began to diminish when the animals reached about 10 months, which is several months before the usual signs of aging start appearing. "By old ageabout two years of age in micemost of those cells were gone," noted Dr. Cai.

The researchers next wanted to learn whether this progressive loss of stem cells was actually causing aging and was not just associated with it. So they observed what happened when they selectively disrupted the hypothalamic stem cells in middle-aged mice. "This disruption, pointed out Dr. Cai, greatly accelerated aging compared with control mice, and those animals with disrupted stem cells died earlier than normal."

Could adding stem cells to the hypothalamus counteract aging? To answer that question, the researchers injected hypothalamic stem cells into the brains of middle-aged mice whose stem cells had been destroyed as well as into the brains of normal old mice.

By replenishing these stem cells or the molecules they produce, it's possible to slow and even reverse various aspects of aging throughout the body, the authors of the Nature article declared. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal miRNAs in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing.

The researchers extracted miRNA-containing exosomes from hypothalamic stem cells and injected them into the cerebrospinal fluid of two groups of mice: middle-aged mice whose hypothalamic stem cells had been destroyed and normal middle-aged mice. This treatment significantly slowed aging in both groups of animals as measured by tissue analysis and behavioral testing that involved assessing changes in the animals' muscle endurance, coordination, social behavior, and cognitive ability.

The researchers are now trying to identify the particular populations of miRNAs and perhaps other factors secreted by these stem cells that are responsible for these antiaging effectsa first step toward possibly slowing the aging process and treating age-related diseases.

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Only as Old as the Brain's Stem Cells Feel - Genetic Engineering & Biotechnology News

Stem cell brain implants could ‘slow ageing and extend life’, study shows – The Guardian

By adminJuly 30, 2017Stell Cell Research

Mice were implanted with stem cells that make fresh neurons in the brain. The cells are found in the hypothalamus in youth, but die off until they are almost completely absent in middle age. Photograph: Alamy Stock Photo

Scientists have slowed down the ageing process by implanting stem cells into the brains of animals, raising hopes for new strategies to combat age-related diseases and extend the human lifespan.

Implants of stem cells that make fresh neurons in the brain were found to put the brakes on ageing in older mice, keeping them more physically and mentally fit for months, and extending their lives by 10-15% compared to untreated animals.

The work, described as a tour de force and a breakthrough by one leading expert, suggests that ageing across the body is controlled by stem cells that are found in the hypothalamus region of the brain in youth, but which steadily die off until they are almost completely absent in middle age.

Researchers at Albert Einstein College of Medicine in New York hope to launch clinical trials of the procedure soon, but must first produce supplies of human neural stem cells in the lab which can be implanted into volunteers.

Of course humans are more complex, said Dongsheng Cai, who led the research. However, if the mechanism is fundamental, you might expect to see effects when an intervention is based on it.

Previous experiments had already hinted that the hypothalamus, an almond-sized part of the brain in humans, played some role in the ageing process, but what it was remained unclear. The latest investigation from the US team pinpoints which cells are important and how they might work.

In the first of a series of experiments in mice, Cai showed that neural stem cells, which are found in a handful of brain regions at birth, disappear from the hypothalamus over time. The stem cells are known to form fresh brain cells in youth, but the process slows down dramatically in adults. Though small, the hypothalamus forms a crucial connection between the bodys nervous and hormonal systems.

To test whether the decline in stem cells was causing ageing, and not itself a result of old age, the researchers injected mice with a toxin that wiped out 70% of their neural stem cells. The effect was striking. Over the next few months the mice aged more rapidly than usual, and performed much worse than control animals on a battery of tests of endurance, coordination, social behaviour and ability to recognise objects. Behaviourally mice aged faster when these cells were removed during early ageing, Cai told the Guardian. The animals died months earlier than healthy control animals.

Next, the scientists looked at what happened when aged mice received injections of fresh neural stem cells. This time the mice lived longer than controls, typically several months more, an increase of about 15%. If a similar extension was achieved in humans, a person with a life expectancy of 80 years could live to 92.

Having proved that it was neural stem cells that were important for ageing, the scientists ran further tests to work out what the cells were doing. They found that molecules called microRNAs, or miRNAs, that are released from neural stem cells were responsible for most of the ageing effects. When the molecules are produced in the hypothalamus, they flow into the clear fluid in the brain and spinal cord and affect how genes operate.

The mechanism is partially due to these cells secreting certain miRNAs which help maintain youth, and the loss of these leads to ageing said Cai, whose study is published in Nature. The next step is to create human neural stem cells in the lab for testing.

It is a tour de force, said David Sinclair at Harvard Medical School. Its a breakthrough. The brain controls how long we live. I can see a day when we are implanted with stem cells or treated with stem cell RNAs that improve our health and extend our lives. I would love to know which brain stem cell secretions extend a mouses lifespan and if human stem cells make them too.

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Stem cell brain implants could 'slow ageing and extend life', study shows - The Guardian

UCI stem cell therapy attacks cancer by targeting unique tissue stiffness – UCI News

By adminJuly 30, 2017Stell Cell Research

Irvine, Calif., July 26, 2017 A stem cell-based method created by University of California, Irvine scientists can selectively target and kill cancerous tissue while preventing some of the toxic side effects of chemotherapy by treating the disease in a more localized way.

Weian Zhao, associate professor of pharmaceutical sciences, and colleagues have programmed human bone marrow stem cells to identify the unique physical properties of cancerous tissue. They added a piece of code to their engineered cells so that they can detect distinctively stiff cancerous tissue, lock into it and activate therapeutics.

Our new type of treatment only targets metastatic tissue, which enables us to avoid some of conventional chemotherapys unwanted side effects, Weian Zhao said. Steve Zylius / UCI

In a study appearing in Science Translational Medicine, the researchers report they have effectively and safely employed this stem cell-targeting system in mice to treat metastatic breast cancer that had spread to the lung. They first transplanted the engineered stem cells to let them find and settle into the tumor site where they secreted enzymes called cytosine deaminase. The mice were then administered an inactive chemotherapy called prodrug 5-flurocytosine, which was triggered into action by the tumor site enzymes.

Zhao said his team specifically focused on metastatic cancer, which comes when the disease spreads to other parts of the body. Metastatic tumors are particularly deadly and the cause of 90 percent of cancer deaths.

This is a new paradigm for cancer therapy, Zhao said. We are going in a direction that few have explored before, and we hope to offer an alternative and potentially more effective cancer treatment.

Zhao added that this stem cell-targeting approach can provide an alternative to many forms of chemotherapy, which has a number of bad side effects. While this widely used method is powerful enough to kill rapidly growing cancer cells, it also can harm healthy ones.

Our new type of treatment only targets metastatic tissue, which enables us to avoid some of conventional chemotherapys unwanted side effects, said Zhao, who is a member of the Chao Family Comprehensive Cancer Center and the Sue & Bill Gross Stem Cell Research Center at UCI.

This published work is focused on breast cancer metastases in the lungs, he added. However, the technology will be applicable to other metastases as well, because many solid tumors have the hallmark of being stiffer than normal tissue. This is why our system is innovative and powerful, as we dont have to spend the time to identify and develop a new genetic or protein marker for every kind of cancer.

So far, the Zhao team has done preclinical animal studies to demonstrate that the treatment works and is safe, and they hope to transition to human studies in the near future. They are currently expanding to include other type of cells, including cancer tissue-sensing, engineered immune-system T cells (called CAR-T) to treat metastasizing breast and colon cancers. They also plan to transform the technology for other diseases such as fibrosis and diabetes, which result in stiffening of otherwise healthy tissue.

Along with Zhao, UCI doctoral students Linan Liu and Shirley Zhang, are co-leading authors of the study. The National Institutes of Health, the Department of Defense, the American Cancer Society and the California Institute for Regenerative Medicine provided support.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. Its located in one of the worlds safest and most economically vibrant communities and is Orange Countys second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit http://www.uci.edu.

Media access: Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UCI faculty and experts, subject to availability and university approval. For more UCI news, visit news.uci.edu. Additional resources for journalists may be found at communications.uci.edu/for-journalists.

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UCI stem cell therapy attacks cancer by targeting unique tissue stiffness - UCI News

Cancer stem cells target of new grant to UCSD scientists – The San Diego Union-Tribune

By adminJuly 30, 2017Stell Cell Research

Californias stem cell agency has awarded $5.8 million to UC San Diego researchers to develop a new variation of cancer immunotherapy.

The California Institute for Regenerative Medicine, or CIRM, approved the grant last week to adapt CAR T-cell technology to fight cancer stem cells. These deadliest of cancer cells have stem cell-like properties that enable them to survive treatments against them and grow profusely. One surviving cell can re-create an entire tumor.

CAR T-cell therapy, pioneered by Dr. Carl June at the University of Pennsylvania, has been used against blood cancers. While not all of those gravely ill patients have survived, a number have experienced dramatic and long-lasting remissions.

UC San Diego Moores Cancer Center physicians led by Ezra Cohen will experiment with the therapy to deal with a variety of hard-to-treat solid tumors. These include head and neck squamous cell carcinoma, triple-negative breast cancer, pancreatic cancer and ovarian cancers. The preliminary research that yielded this potential treatment was funded by the San Diego-based Immunotherapy Foundation.

Heres how CAR T-cell therapy works: Doctors genetically engineer a patients T cells, part of the immune system, to recognize a protein, called an antigen, on cancer cells so they can destroy them.

The T cells are given what is called a chimeric antigen receptor, or CAR. This is an artificial construct that can recognize the antigen on cancer cells, signaling the immune system to attack. The antigen targeted varies with different versions of the technology.

The T cells are removed from the patient, given the cancer-fighting receptor construct, grown to sufficient numbers, then re-infused into the patient. The cells act as living drugs. They tend to stick around in the patient, ready to grow and attack again if the cancer recurs.

While this has been demonstrated in blood cancers, solid tumors pose a more difficult problem, because immune cells have more limited access to the interior of these tumors.

Cohen, associate director for translational science at UC San Diego Moores Cancer Center, is a specialist in head and neck cancer. Among his patients: Ricki Rockett, the drummer from the band Poison.

Rockett, facing amputation of his tongue when he met Cohen, was given another kind of cancer immunotherapy, two drugs called checkpoint inhibitors that remove a molecular cloak that cancer cells use to hide from the immune system.

The treatment worked. The cancer disappeared, and Rocketts tongue was saved.

Its one year after his complete response, and hes still cancer-free, Cohen said. Rockett also went on tour with the band.

Cohen said the newly funded work with CAR T cells builds on earlier UC San Diego research that identified a receptor on some cancer cells as a promising new target. Its made in both solid tumors and blood cancers, but not in normal cells.

The receptor, tyrosine kinase-like orphan receptor or ROR1, is the target of a drug now being tested by Cohens colleague Dr. Thomas Kipps in patients with relapsed or refractory chronic lymphocytic leukemia. The drug, a monoclonal antibody called cirmtuzumab, is named after CIRM, which funded the research that produced the drug.

ROR1 is produced almost exclusively in the embryonic and early fetal stage, and helps the nascent tissues migrate to the right parts of the body, Cohen said. It appears to have virtually no use after that stage. So it appears to be a safe target. Thats been a challenge to find with cancer stem cells, because their genetic activity somewhat resembles that of normal stem cells.

For obvious reasons you don't want to eliminate all the stem cells in a person's body, Cohen said.

Theres some hints ROR1 might be produced in certain precursors to B cells, which are immune cells that make antibodies, he said. Its possible to live without B cells, as in the case where drugs destroy B cells to stop B-cell lymphoma.

The new project was sparked by Kipps research indicated that ROR1 was produced in high amounts in the hard-to-treat cancers. Cohen began thinking of how this knowledge could be applied with CAR T-cell technology

Cohen said preclinical research has already been performed for the new project. In cell culture tests, CAR T cells with the ROR1 receptor kill cancer stem cells with the receptor in those difficult cancers.

Funding for that research came from the Immunotherapy Foundation, created by San Diego philanthropists Ralph and Fernanda Whitworth in 2015 after Ralph Whitworth was diagnosed with cancer. He died of the disease in September 2016.

Christina Martinez, the Immunotherapy Foundations executive director, said Whitworth met with Cohen after his diagnosis, and became personally interested in advancing the research.

It was a serendipitous encounter, but he really saw the potential for a lasting partnership in his ability to be able to make a long-term contribution to the area of immunotherapy, Martinez said. This project was just one that fell under kind of an umbrella of projects that he was interested in and funding at UCSD. So he and Fernanda seeded that initial investment.

To further improve cancer immunotherapy, the Whitworths established the Immunotherapy Foundation. Fernanda Whitworth, president and co-founder, said shes pleased with the progress.

Ralph and I liked that these projects were designed to be tightly interconnected to leverage information and allow efficient movement into the clinic, she said. Today, I am proud to see this rational, focused approach is working.

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Cancer stem cells target of new grant to UCSD scientists - The San Diego Union-Tribune