Monthly Archives: April 2019

CAR T-cell therapy giving new hope to cancer patients …

Last Updated Apr 2, 2019 11:11 AM EDT

In 2016, 10th grade student Sally Naser learned she had a cancerous growth on both her lungs. She had first been diagnosed with a tumor, a type of bone cancer called sarcoma, at age 10. This was her third relapse.

"One of the doctors advice was, 'I think now's a good time to take a family vacation,'" said Camille Naser, her mother. "We said and Sally said, we weren't quite ready to give up."

There was one last option. Sally joined a trial at Baylor College of Medicine using a therapy called CAR T. First, doctors removed some of Sally's T-cells, infection fighting white blood cells, and genetically modified them to recognize her sarcoma cancer as being enemy cells that should be destroyed. Millions of those new cells were then put back in Sally's body, ready to search out and destroy the cancer.

"It just took 20 minutes and they're like, alright, that's it," Sally Naser said.

Of 10 patients, three have stable disease and two, including Naser, have no evidence of cancer. Two CAR T therapies are already FDA approved for forms of leukemia and lymphoma. The next hurdle is proving it works on solid tumors like lung, colon and sarcoma.

"Solid tumors, many of which are very, very difficult to treat, represent a huge burden of cancer and morbidity and mortality," said Dr. Louis Weiner, with the American Association for Cancer Research and Georgetown Lombardi Comprehensive Cancer Center.

Naser is now a freshman at the University of Massachusetts at Amherst.

"This is the longest that it's been ever without a recurrence," she said. "That gives me hope that you know, the treatment actually worked."

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Pathways to Stem Cell Science | Intro to Stem Cell Systems

Description

Intro to Stem Cell Systems is an introductory five-day course that explores the exciting science of stem cell research and regenerative medicine. Designed for entry-level scientists, this innovative program provides foundational training in bioscience techniques and essential principles in human stem cell biology. Participating students study the three-major human stem cell systems adult, cancer and pluripotent, through laboratory classes and engaging college-level lectures covering the science, history and ethics of stem cell research. They learn modern skills used by a variety of bioscience professions, working hands-on in a biotech laboratory with cancer, neural and induced pluripotent stem cells.

Each day of the program focuses on a different aspect of stem cell biology, taking students on a stimulating journey from basic discovery to therapeutic translation. Course participants are also introduced to independent research skills, during "stem cell fact or fiction" an interactive lecture-discussion which demonstrates real-life methods for finding published research and applying scientific data to debunk stem cell myths. The program ends with a career development seminar focusing on the many career paths available to bioscientists, led by science professionals with academic and industry experience. This unique course is suited to any motivated science student with an interest in learning more about stem cell research and its current real-world application.

College-level lectures Hands-on lab classes Cutting edge techniques* Guest speakers Literature research Career education Networking with professional science mentors

*Intro to stem cell systems provides practical training in: BSL-2 lab safety procedures, stem cell culture, aseptic technique, tissue microdissection, cell derivation, stem cell isolation, electroporation, antibody labeling and microscopy (phase contrast and fluorescent).

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Risky Stem-Cell Treatments Come Under F.D.A. Scrutiny …

Cord for Life also fared poorly on an F.D.A. inspection in November, according to the letter, which listed numerous deficiencies in sanitation, like employees wearing the same non-sterile smocks for up to two weeks, not changing gloves and not cleaning equipment properly.

The F.D.A. gave the company 15 days to present a plan for correcting the deficiencies, and noted that failing to act on the problems could result in seizure and/or injunction by the agency.

Donald Hudspeth, general manager of Cord for Life, said the company had already corrected the problems identified in the inspection. Mr. Hudspeth also said that Cord for Life was unaware that the F.D.A. expected it to submit more proof of completion.

In addition, he said the company had not received any reports of adverse reactions from its products in its 25-year history.

The F.D.A. did not release the names of the recipients of the other 20 letters.

In their statement, Dr. Gottlieb and Dr. Marks dismissed claims by some stem cell businesses that they are exempt from F.D.A. regulations because their practitioners extract stem cells from a patients own fat or bone marrow and then return the cells to the same patient. The cells do not qualify as drugs and do not need regulation, the clinics argue.

The two officials disagreed: Stem cell products can create unique and serious risks depending on how theyre manipulated once theyre taken from the body and how they are used once theyre reinserted in the body.

The statement also noted that the F.D.A. was halfway through a three-year period of what it calls enforcement discretion, meaning that in 2017 it put stem-cell clinics on notice that their treatments were likely to come under F.D.A. authority, but that instead of cracking down immediately it was giving them time to learn what rules applied to them and to comply.

So far, though, the industrys response has been modest, the agency said, adding that once the three-year period is over, in November 2020, well step up our oversight.

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Gene therapy-corrected autologous hepatocyte-like cells …

Our research group has been able to successfully develop induced pluripotent stem cells from patients with arginase deficiency, a poorly treated metabolic disorder of the liver that results in intellectual disabilities. In this disorder, the enzyme argianse is mutated and does not function in a normal process called the urea cycle which handles nitrogen metabolism. An excess of nitrogen in the body (through netabolism, diet, injury, or illness), typically as ammonia, can cause brain injury. We have been able to successfully introduce a normal copy of the arginase gene into induced pluripotent stem cells  from the patient-derived cells and then developed them into hepatocyte-like cells. At the same time, we have been utilizing a mouse model of arginase deficiency that was further modified to carry genes that suppress their immune system. We have been able to repopulate the liver of these mice with normal human hepatocytes that has led to correction of the defect related to arginase deficiency. These animals demonstrate almost normal circualting blood levels of arginine and ammonia and have improved handling of nitrogen when it is delivered to the mice as an ammonia injection. At present, the induced pluripotent-derived hepatocytes have not engrafted in these mice,and  we are continuing to work on strategies to lead to engraftmentment and thus treatment of this disorder. The ultiamte goal of treatment is to be able to take skin cells from a patient with this disorder, develop them into stem cells, add a corrected copy of the arginase gene, develop these cells into hepatocytes and deliver them to the same patient's liver to correct the disorder. WIth the data to date we are on our way to achieving this goal.

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Embryonic Stem Cell: Definition, Uses and Collection …

Embryonic Stem Cell Definition

An embryonic stem cell is a cell derived from the early stages of an embryo which is capable of differentiating into any type of body cell. Embryonic stem cells are capable of differentiating into any cell type because in the embryo that is what they are used for. As the embryo grows and divides, cells which are generalized must become more and more specific as they divide. This eventually creates the different organs, tissues, and systems of an organism.

After the sperm reaches an egg (oocyte), fertilization occurs and the DNA from the two cells merge into a single nucleus, in a single cell. This is the zygote, and is technically an embryonic stem cell because as it divides it will differentiate into all of the cells of the body. This cell, and the first few divisions of this cell, are totipotent. This means that they have the ability to become an entire organism. Identical twins, for example, develop from the same zygote which accidentally separates when it begins to divide.

In medicine and research, scientist use pluripotent embryonic stem cells. These cells do not have the ability to become an entire organism. Rather, they are directed by signals from the early embryo which tell them which cell type to differentiate into. Scientists prefer these cells for many reasons. First, they can be stored and maintained more easily. Totipotent cells have a tendency to differentiate quickly, and immediately try to become an organism. Pluripotent cells are waiting for a signal to divide, and can be maintained for longer periods. Further, because pluripotent cells are simply waiting for the proper signals to tell them which cell type to become, they can easily be integrated into medical applications in which new tissue must be grown.

There are also other types of stem cells, not to be confused with an embryonic stem cell. Embryonic stem cells are derived from embryos. There are also adult stem cells, umbilical cord stem cells, and fetal stem cells. Not only are these stem cells sometimes more ethically challenging, they are only multipotent, meaning they can only become a small range of cell types.

The use of embryonic stem cells is a very new form of medicine. For decades, the cause of many degenerative diseases and physical injuries has been understood. Tissue damage is the root cause of many of these ailments, and scientist have long been searching for a method of growing tissues which do not easily repair themselves. Because an embryonic stem cell is pluripotent, and can become almost any cell in the body, these cells have long been studied for their possible use in medicine.

Since the late 1950s scientists have been trying to test various methods of growing tissue with an embryonic stem cell. The first clinical trials were in the late 1960s, but not much progress has been made. President Bush put a moratorium on using Federal funds for stem cell research, which was finally lifted by the Obama Administration in 2009. European countries have also faced an uphill battle in funding stem cell research. However, with advances in the science came new discoveries which allowed for more ethical harvesting of an embryonic stem cell. The first treatments with medicinal stem cells were in 2010.

Medically, the embryonic stem cell is limited in its current uses, though many novel applications are in the works. Current treatments focus on the replacement of damaged tissue from injury or disease. Of these, the first treatment approved by the FDA to undergo trials was replacing damaged tissue in spinal injuries. Because nerve cells rarely regenerate, an embryonic stem cell can be used to replace the damage nerve and restore function. In someone with a spinal injury, this means being able to walk again. For a blind person, this might mean being able to see again. While the treatment is still new and success is limited, it has shown some positive results.

Still other medical advances are made with the embryonic stem cell, although these dont come as direct medical treatments but rather as the knowledge that stem cells give us. As an embryonic stem cell differentiates into its target tissue, scientists can study the chemicals and methods it uses to do so. Scientists can also alter the genome of these cells, and study the effects different mutations have on a cells functioning. Between these two paths of discovery, scientists have assembled much information about how and why cells differentiate and divide. Using these tools, scientists are closing in on methods which would allow them to turn regular cell back into a pluripotent stem cell. This process could not only fix injuries and ailments, but could potentially reverse aging and prevent death.

On a less dramatic and grand scale, these methods are also being used to cure common diseases, such as diabetes. By learning how embryonic stem cells become pancreas cells and secrete insulin, scientists are learning the methods of converting other tissues to insulin-secreting tissues. This could help cure diabetes, often caused by the destruction of insulin producing cells. If these were replaced with stem cells, or other cells were induced to become pancreas cells, the disease could be cured. Other diseases, like cystic fibrosis, fragile x syndrome, and other genetic disorders are studied in embryonic stem cells. Not only can many cells be created, but they can be differentiated into different cell types. In this way, a scientist can build a picture of the disease from snapshots of each cell type, and understand exactly how the disease is affecting a person.

While there was once a concern that embryonic stem cells were being harvested without consent from unknowing women, the vast majority are now ethically harvested an in vitro fertilization clinics. In these clinics, in order to get a successful pregnancy, many eggs must be fertilized. Only one is implanted, and with the womans consent the rest can be used to harvest embryonic stem cells. To do this, scientists extract some embryonic stem cells from an embryo when it is only a small ball of cells. This can be seen in the image below.

A harvested embryonic stem cell is placed in a petri dish with nutrients and is allowed to divide. Without any signals from the embryo, the cells remain pluripotent. They continue dividing, fill one dish, and they are transferred to many more dishes and continue to grow. After 6 months of this, they are considered a successful pluripotent embryonic stem cell line. They can then be used to study disease, be used in treatments, or be manipulated genetically to provide models for how cells work.

To test that these cells are indeed pluripotent stem cells, they are injected into mice with depressed immune systems. The mice must have depressed immune systems, or their bodies would naturally reject the human tissue. Once implanted into the mouse, successful pluripotent cells will form a small tumor called a teratoma. This small tumor has different tissue types, and proves that the cell line is still pluripotent and can differentiate into different cell types.

There are a number of other types of stem cells, besides embryonic stem cells. These cells come from different sources and can be used for different purposes. Often, they are only multipotent, and can transform into only a narrow range of cell types. One example is umbilical cord blood stem cells, which have been used in medical treatments to treat various blood diseases and suppressed immune systems. The stem cells in the blood of the umbilical cord can differentiate into almost any type of blood or immune cell, making them multipotent. However, this limits their use in other areas of medicine.

There are also adult stem cells, which survive in various organs throughout the body. These cells are also multipotent, and can only differentiate into the kinds of tissue in which they are found. A common use of adult stem cells is the bone marrow transplant. In this procedure a healthy donor must have their marrow extracted from their bones. The marrow is a blood-like substance on the inside of large bones which creates blood cells and immune cells. Cancer patients, having undergone radiation and chemotherapy, lose most of their immune cells and become immunocompromised. Often a bone marrow transplant is needed to replace these tissues. The new stem cells begin producing new immune cells, which help the patient recover and fight off infection and disease.

1. What is the difference between pluripotent and multipotent stem cells? A. There is no difference B. Pluripotent cells can become a wider variety of cell types C. Multipotent cells can become a wider variety of cell types

Answer to Question #1

B is correct. Pluripotent embryonic stem cells are one step below totipotent stem cells. These pluripotent cells can become almost any cell type in the body, except the cells needed to support a developing embryo. Multipotent cells are already differentiated to a specific degree, and are restricted to creating only a few types of cells.

2. At a certain stage, embryonic stem cells are totipotent. Why dont scientists use these stem cells? A. These cells have the potential to become an entire organism B. The pluripotent stem cells can become more cell types C. Totipotent cells cannot survive in the lab

Answer to Question #2

A is correct. Because totipotent cells have the potential to become an entire organism, they will actively work to do so. That means that whether they are in the lab or in the womb, they will try to direct the development of an organism. They do this by releasing hormones and chemicals which cause the cells to divide and differentiate. Pluripotent cells can be suspended in a generalized state, which makes them better candidates for study and medical procedures.

3. Which of the following ailments cannot potentially be treated with stem cells? A. Brain injury B. Diabetes C. Cancer

Answer to Question #3

C is correct. While the side-effects from treating cancer are treated with stem cells (see above on bone marrow transplants), treating the actual cancer is done with radiation and chemotherapy. These treatments also kill the rapidly dividing stem cells in a persons body, which is why they must be replaced.

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Embryonic Stem Cell: Definition, Uses and Collection ...

Stem cell clinics make big claims but offer little …

If someone says they have a success rate of close to 100 percent in treating a major health problem but offer little evidence to back that up, you might be excused for being more than a tad skeptical. And a new study says you would be right.

The health problem in question is osteoarthritis (OA) of the knee, something that affects almost 10 million Americans. Its caused by the wearing down of the protective cartilage in the knee. That cartilage acts as a kind of shock absorber, so when its gone you have bone rubbing against bone. Thats not just painful but also debilitating, making it hard to lead an active life.

There is a lot of research taking place including a clinical trial that CIRM is funding that focuses on using stem cells to create new cartilage, but so far nothing has been approved by the US Food and Drug Administration for wider use. The reason for that is simple. No approach has yet proven it is both safe and effective.

No evidence? No worries

But that doesnt stop many clinics around the US, and around the world, from claiming they have treatments that work and charging patients a hefty sum to get them.

In a study presented at the Annual Meeting of the American Academy of Orthopaedic Surgeons, researchers contacted 317 clinics in the US that directly market stem cell therapies to consumers. They asked the clinics for information on the cost of the procedure and their success rate.

Only 36 clinics responded with information about success rates.

None offered any evidence based on a clinical trial that supported those claims, and there was no connection between how much they charged and how successful they claimed to be.

In a news release about the study which appears in the Journal of Knee Surgery George Muschler, one of the lead authors, said that orthopedic surgeons have a duty to give patients the best information available about all treatment options.

Recent systematic reviews of cellular therapies for the treatment of knee OA (over 400 papers screened) have found poor levels of evidence for the efficacy of these treatments to date. Current evidence does not justify the rapid rate of growth for these therapies.

Nicolas Piuzzi, the other lead author on the study, says if the evidence doesnt justify the growth in the number of clinics offering these therapies, it certainly doesnt justify the prices they charge.

The claim of stem cell therapy carries a high level of expectations for the potential benefits, but research is still many years away from providing clear evidence of effective treatment to patients. As clinicians and researchers, we have ethical, scientific, legal and regulatory concerns. Patients need to be aware of the status of research within the field. If they receive information from anyone offering a treatment claim of an 80 to 100 percent successful recovery, they should be concerned in observance of published peer-reviewed evidence.

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UCLA UCI Alpha Stem Cell Clinic | UCLA Broad Stem Cell Center

...part of the CIRM Alpha Stem Cell Clinic Network

The UCLA-UCI Alpha Stem Cell Clinic (ASCC) accelerates the implementation of clinical trials and delivery of stem cell therapies by providing world-class, state-of-the-art infrastructure to support clinical research.

The UCLA-UCI ASCC is a first-of-its-kind collaboration between the University of California, Los Angeles, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and the University of California, Irvine Sue & Bill Gross Stem Cell Research Center. It is one of five clinics (alongsideCity of Hope, UC Davis, UC San Diego, and UC San Francisco) funded through an $8M grant from theCalifornia Institute for Regenerative Medicine (CIRM),the states stem cell agency. These five Alpha Clinics comprise the CIRM Alpha Stem Cell Clinics Network.

For more information onclinical trials at the UCLA-UCI ASCC that are active and recruiting, please visit the current clinical trials page. The 'detail' option provides specific information for each trial, including a link to each trial'sClinicalTrials.gov page (via the NCT number). ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world.

For a complete list of clinical trials across the CIRM Alpha Stem Cell Clinics Network, please visitCIRM's ASCC clinical trials page.

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UCLA UCI Alpha Stem Cell Clinic | UCLA Broad Stem Cell Center

Stem cell clinics sued | Regenerative Medicine Foundation

Columnist Mitchell Hiltzik savaged the La Jolla-based StemGenix Medical Center The stem cell therapies offered by La Jolla clinic arent FDA approved, may not work- and cost $15,000 reads the title of his pieceon the LA Times. StemGenix is the subject of a federal class-action lawsuit.

Hiltzik calls for the FDA and state medical boards to act now, stating that the clinics are endangering their customers health and draining their pocketbooks for quack remedies, shut them down.

Its not that easy.

Cell therapies in clinical practice are expanding worldwide, at a pace difficult to measure. Its wishful thinking to imagine a regulatory police force shutting down all the bottom feeders and rip-off clinic peddling false claims.

Patientsare eager, if not desperate, to undertake medical treatments to alleviate their debilitating medical conditions- especially where drugs and surgeries have failed them.

Medical doctors want to incorporate into their practices legitimate cell therapies. Not only are they answering consumer demand. Broadening anecdotal evidence shows positive results. It the practice of medicine, unconstrained by reimbursement paperwork, meaning the patient pays up front.

In the meantime, some in industry see regenerative medicine as a negative disruptive force- potentially impacting their companys bottom lines. After all, if an autologous cell therapy alleviates the pain, who will buy the drug?

Moreover, numerous stakeholders lay claim to the brands stem cells and regenerative medicine. Lofty scientific organizations such as the International Society for Stem Cell Research (ISSCR) should be uncomfortable about clinic that brands its PRP protocols as a stem cell treatment. Theres lot of confusion.

Now, into this muddled landscape, come the lawsuits. A good lawsuit has always been a deterrent to bad behavior.

In the StemGenix case, the plaintiffs are three former patients, two with diabetes and one with lupus. There is no allegation of medical malpractice. Plaintiffs counsel shrewdly deploys a smack-down of claims citing California consumer protection laws, false advertising, violations against human experimentation, fraud, financial elder abuse and the crown jewel- a violation of the Racketeer Influenced and Corrupt Organizations Act (RICO), the federal law designed to combat organized crime in the United States- but wielded in civil lawsuits where the allegedly corrupt enterprise encompasses interstate commerce.

That lawsuit, and the monumental publicity surrounding the recently settled Florida case, where a patient was blinded by an alleged stem cell treatment, suggest that the legal floodgates are now open. It will take an extremely well capitalized clinic to withstand damage claims, litigation costs including attorney fees and a bucket full of bad publicity.

Into the breach, communities of professionals such as the American Academy of Regenerative Medicine (AARM) and the International Federation for Adipose Therapeutics and Science (iFats) are now advancing agendas committed to evidence-based medicine, codes of ethics, standards and educational programs to ensure medical practitioners have the proper skills.

The field really could benefit from a universal cell therapy registry where results can be openly shared. In the United States, there are models of funded registries for organ transplant and cell transplantation. Joining the registry could serve as a seal of approval for those sharing outcomes, reflecting transparency and a commitment to the field.

In the meantime, for the bad clinics, one negative clinical outcome, a single disgruntled customer, can sink their ship. The lawyers know a good thing when they see it. They are eagerly sharpening their quills.

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Patients fleeced by overseas stem cell clinics? Now it …

Alta Charo, Warren P. Knowles professor of law and bioethics at the University of Wisconsin-Madison, is pictured in July 2013.(Photo: Jeff Miller, University of Wisconsin-Madison)

Three women between the ages of 72 and 88 suffered severe loss of vision after receiving injections of stem cells derived from their own fatty tissue, according to a 2017 paper in The New England Journal of Medicine. All three had paid $5,000 to a stem cell clinic in Sunrise, Florida.

In 2009, a Los Angeles woman in her late 60s had to have small chunks of bone removed from the tissue around her eye, after undergoing a new face-lift procedure that included an injection of stem cells, Scientific American reported.

The cells, obtained from her own fat, included mesenchymal stem cells thathelp form skeletal tissue, including bone and cartilage.

A decade ago, U.S. scientists worried about Americans flying thousands of miles and spending thousands of dollars only to get fleeced by stem cell clinics in the regulatory Wild West of countries like China, India, Mexico and Thailand.

Now it happens here.

RELATED: 20 years after the growth of human embryonic stem cells at UW, science faces new frontiers

Leigh Turner, an associate professor for bioethics at the University of Minnesota, found 716 stem cell clinics in the U.S and published a paper on the phenomenon in the journal Perspectives in Biology and Medicine.

Turner found many of the clinics claimed to use stem cells taken from the patients own fat; others said they use blood-forming stem cells obtained from bone marrow. The latter have been used for years to treat some cancers, mostly leukemia and lymphoma.

Turner discovered, however, that stem cell clinics are promoting their cells as treatment for a wide variety of illnesses, including orthopedic conditions, pain relief, neurological disorders, immunological diseases, cardiovascular diseases, kidney diseases, respiratory diseases, Alzheimers, aging, dental problems, vision loss, hearing loss and even hair loss.

The long list of applications for one treatment, experts say, is a tip-off that the claims are dubious.

Its extraordinarily unlikely that a single product is going to have a positive effect on a whole series of diseases, saidAlta Charo, a University of Wisconsin-Madisonprofessor of law and bioethics.

In his paper, Turner said that the FDA, FBI, the Federal Trade Commission and state medical boards all have powers to regulate various aspects of the burgeoning stem cell business.

However the appearance of a well-regulated and strictly overseen marketplace for stem cell products is misleading, Turner wrote. Many U.S. businesses currently advertising stem cell treatments appear to operate in violation of federal regulations because they lack FDA approval for products that require premarket authorization.

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There have been some enforcement actions. In 2017, FDA announced a crackdown aimed at unscrupulous actors in the stem cell business. Earlier this year the agency filed complaints seeking permanent injunctions against two stem cell firms: U.S. Stem Cell Clinic LLCof Sunrise, Florida, and California Stem Cell Treatment CenterInc.of Rancho Mirage, California.

John Gurdon, the Nobel Prize-winning British scientist, said by email that clinics using unproven treatments coulddamage public confidence in stem cell research.

I believe all medical treatments should be conducted based on sufficient scientific evidence, said Gurdon, who shared the 2012 Nobel Prize in Physiology or Medicine with Japanese stem cell scientist Shinya Yamanaka. Unproven treatments can, not only impose huge physical and financial risks on patients, but also lose the credibility of stem cell research. Our first priority should be to ensure patients safety as much as we can.

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