Stem Cell Clinic

Fighting Pediatric Sickle Cell Anemia – Touro College News

This is the question TouroCOM student Stephanie Chung examined this summer at the pediatric hematology oncology department at Akron Childrens Hospital in Ohio. Chung, who has done research at Cornell University in the past, said that the general usage rate for the drug is between 10-25 percent (the number at Akron is significantly higher, between 90-100 percent). There are a variety of reasons for the underutilization, Chung explained, from lack of communication between primary care providers and oncologists to the intense clinical schedule that hydroxyurea requires.

Parents might also be leery of the drug since it is also used in cancer treatment. As a volunteer EMT in her hometown of Lodi, NJ, Chung said she was used to working with the elderly, but working with parents and children is a new experience for her. When you treat adults its a one-on-one relationship, said Chung. As a pediatrician, you have to work with both the parent and the patient. She plans to publish a paper about the underutilization of hydroxyurea and an additional paper about the social media discussions occurring around the drug.

Chung also believes that a new approach is needed for the drug.

Hydroxyurea decreases the rate of organ damage, said Chung. The way you have to approach the use of the drug is that its a preventative measure instead of using it for a pain crisis.

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Immunotherapy Shown Safe in Type 1 Diabetes Clinical Trial – Sioux City Journal

WEDNESDAY, Aug. 9, 2017 (HealthDay News) -- A small clinical trial showed an immune system therapy was safe for people with type 1 diabetes, British researchers report.

The immunotherapy also showed signs of helping to keep insulin production steady in people newly diagnosed with the disease, the study authors said. However, because this was a placebo-controlled safety trial, there weren't enough people included to know for sure how well the treatment works.

The therapy is similar to an allergy shot in the way it works, the researchers explained.

"Type 1 diabetes comes about when the immune system inadvertently and irreparably damages beta cells that make insulin," said one of the study's authors, Dr. Mark Peakman. He's a professor of clinical immunology at King's College London in England.

Insulin is a naturally occurring hormone that helps usher the sugar from foods into the body's cells to be used as energy. If the immune system continues to attack the beta cells, which are found in the pancreas, a person with type 1 diabetes will no longer make enough insulin to meet the body's needs. It's at this point that they must take insulin injections or use an insulin pump to replace the lost insulin.

Peakman and his colleagues are trying to stop the attacks on the beta cells.

"We have learned that immune attacks like this can be suppressed by immune cells called T-regs (regulatory T cells)," Peakman said.

When people develop type 1 diabetes, it's likely that they don't have enough of the right type of T-regs or those T-regs aren't working very well. So, the investigators developed a type of treatment called peptide immunotherapy using disease-related autoantigens.

Autoantigens are the substances that cause an autoimmune attack, but it's not clear which ones are responsible for a person's diabetes, according to Simi Ahmed, a senior scientist at JDRF (formerly the Juvenile Diabetes Research Foundation) in New York City.

Ahmed said the immunotherapy re-educates the immune system, and teaches the cells that they shouldn't attack the beta cells.

Peakman pointed out that the researchers "used peptide immunotherapy as a way to try and induce more of these cells and/or make them work better. Our results show encouraging signs that this can be achieved. Next steps will be bigger trials to test whether the therapy can halt beta cell damage."

And, he added, "Scientists think this works by enhancing natural immune networks that control inflammation."

The study included 27 people with type 1 diabetes who had been diagnosed with the disease within 100 days. The study volunteers were randomly selected to be in one of three groups: a placebo group; a group given immunotherapy once every four weeks; and a group that received the immunotherapy injection once every two weeks.

The study team measured levels of a substance called C-peptide, which is created when insulin is produced. Stable or increasing levels of C-peptide indicate that insulin is being made. Declining levels indicate that less insulin is being made.

The volunteers given immunotherapy once every four weeks saw no decline in C-peptide, the findings showed. The group given the treatment once every two weeks saw a decrease in C-peptide at the 12-month mark. Those given a placebo had decreased C-peptide levels at 3, 6, 9 and 12 months.

Peakman said there weren't enough people in the study to know why there were slight differences in the treatment groups. That's for a larger study to figure out, he suggested.

But the researchers found that the treatment was quite safe, and there were no side effects "of note," Peakman added.

The study also looked at insulin use. Over 12 months, insulin use went up by 50 percent in the placebo group. But there was no increase in the treated groups.

And even though all the study volunteers still needed insulin, both diabetes experts said that the need for less insulin would likely improve quality of life and lessen complications.

It's not yet clear from this trial how often the treatment would need to be given to keep the immune attack at bay.

It's also not clear if it could benefit people who've had type 1 diabetes for a while. Peakman said it probably wouldn't help them because most of their beta cells would be gone. But Ahmed noted that if someone had detectable C-peptide levels, it's possible that this treatment or future ones that may contain more than one autoantigen might have an effect.

In December 2016, a study published in Diabetologia found that about one-third of people with type 1 diabetes for at least 10 years still had detectable C-peptide levels. And two-thirds of them showed signs of an ongoing immune system attack.

Findings from the new study were published Aug. 9 in Science Translational Medicine.

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Immunotherapy Shown Safe in Type 1 Diabetes Clinical Trial - Sioux City Journal

Stem cells may treat lung fibrosis diseases – Futurity: Research News

Researchers have taken a step towards a possible treatment for several often-fatal lung conditions that affect millions of Americanssuch as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and cystic fibrosisby harvesting and using lung stem cells.

In research appearing in the journal Respiratory Research, the scientists demonstrated that they could harvest lung stem cells from people using a relatively non-invasive, doctors-office technique. They were then able to multiply the harvested lung cells in the lab to yield enough cells sufficient for human therapy.

In a second study, which appears in the journal Stem Cells Translational Medicine, the team showed that, in rodents, they could use the same type of lung cell to successfully treat a model of IPFa chronic, irreversible, and ultimately fatal disease characterized by a progressive decline in lung function.

The researchers have been in discussions with the FDA and are preparing an application for an initial clinical trial in patients with IPF.

This is the first time anyone has generated potentially therapeutic lung stem cells from minimally invasive biopsy specimens, says co-senior author of both papers Jason Lobo, an assistant professor of medicine at the University of North Carolina at Chapel Hill and medical director of lung transplant and interstitial lung disease.

We think the properties of these cells make them potentially therapeutic for a wide range of lung fibrosis diseases.

Co-senior author Ke Cheng, an associate professor in North Carolina State Universitys molecular biomedical sciences department and UNC/NCSUs joint biomedical engineering department, says, We think the properties of these cells make them potentially therapeutic for a wide range of lung fibrosis diseases.

These diseases of the lung involve the buildup of fibrous, scar-like tissue, typically due to chronic lung inflammation. As this fibrous tissue replaces working lung tissue, the lungs become less able to transfer oxygen to the blood. Patients ultimately are at risk of early death from respiratory failure.

In the case of IPF, which has been linked to smoking, most patients live for fewer than five years after diagnosis.

The two FDA-approved drug treatments for IPF reduce symptoms but do not stop the underlying disease process. The only effective treatment is a lung transplant, which carries a high mortality risk and involves the long-term use of immunosuppressive drugs.

Scientists have been studying the alternative possibility of using stem cells to treat IPF and other lung fibrosis diseases. Stem cells are immature cells that can proliferate and turn into adult cells in order to, for example, repair injuries. Some types of stem cells have anti-inflammatory and anti-fibrosis properties that make them particularly attractive as potential treatments for fibrosis diseases.

Cheng and Lobo have focused on a set of stem cells and support cells that reside in the lungs and can be reliably cultured from biopsied lung tissue. The cells are called lung spheroid cells for the distinctive sphere-like structures they form in culture.

As the scientists reported in an initial paper in 2015, lung spheroid cells show powerful regenerative properties when applied to a mouse model of lung fibrosis. In their therapeutic activity, these cells also outperform other non-lung-derived stem cells known as mesenchymal stem cells, which are also under investigation to treat fibrosis.

In the first of the two new studies, Lobo and his team showed that they could obtain lung spheroid cells from human lung disease patients with a relatively non-invasive procedure called a transbronchial biopsy.

We snip tiny, seed-sized samples of airway tissue using a bronchoscope, Lobo says. This method involves far less risk to the patient than does a standard, chest-penetrating surgical biopsy of lung tissue.

Cheng and his colleagues cultured lung spheroid cells from these tiny tissue samples until they were numerous enoughin the tens of millionsto be delivered therapeutically. When they infused the cells intravenously into mice, they found that most of the cells gathered in the animals lungs.

These cells are from the lung, and so in a sense theyre happiest, so to speak, living and working in the lung, Cheng says.

For the second study, the researchers first induced a lung fibrosis condition in rats. The condition closely resembled human IPF. Then the researchers injected the new cultured spheroid cells into one group of rats. Upon studying this group of animals and another group treated with a placebo, the researchers saw healthier overall lung cells and significantly less lung inflammation and fibrosis in the rats treated with lung spheroid cells.

Our vision is that we will eventually set up a universal cell donor bank

Also, the treatment was safe and effective whether the lung spheroid cells were derived from the recipients own lungs or from the lungs of an unrelated strain of rats, Lobo says. In other words, even if the donated stem cells were foreign, they did not provoke a harmful immune reaction in the recipient animals, as transplanted tissue normally does.

Lobo and Chen expect that when used therapeutically in humans, lung spheroid cells initially would be derived from the patient to minimize any immune-rejection risk. Ultimately, however, to obtain enough cells for widespread clinical use, doctors might harvest them from healthy volunteers, as well as from whole lungs obtained from organ donation networks. The stem cells could later be used in patients as-is or matched immunologically to recipients in much the same way transplanted organs are typically matched.

Our vision is that we will eventually set up a universal cell donor bank, Cheng says.

Cheng, Lobo, and their teams are now planning an initial study of therapeutic lung spheroid cells in a small group of IPF patients and expect to apply later this year for FDA approval of the study. In the long run, the scientists hope their lung stem cell therapy will also help patients with other lung fibrosis conditions of which there are dozens, including COPD, cystic fibrosis, and fibro-cavernous pulmonary tuberculosis.

Additional researchers contributing to this work are from UNC, NC State, the joint UNC-NC State biomedical engineering department, and two hospitals in Shijiazhuang, China. The National Institutes of Health, the UNC General Assembly Research Opportunities Initiative, and the NC State Chancellors Innovation Fund funded this research.

Source: UNC-Chapel Hill

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Stem cells may treat lung fibrosis diseases - Futurity: Research News

New device can heal with a single touch, and even repair brain injuries – USA TODAY

A new device has been developed at The Ohio State University, which turns cells into other types of cells required for treating diseased conditions. During testing, one touch completely repaired injured legs of mice over three weeks! USA TODAY

Researchers demonstrate a process known as tissue nanotransfection at The Ohio State University Wexner Medical Center. In laboratory tests, this process was able to heal the badly injured legs of mice in just three weeks with a single touch of this chip. The technology works by converting normal skin cells into vascular cells, which helped heal the wounds.(Photo: The Ohio State University Wexner Medical Center)

A new device developed at The Ohio State University can start healing organsin a "fraction of a second," researchers say.

The technology, known asTissue Nanotransfection (TNT), has the potential to save the lives of car crash victims and even deployed soldiers injured on site. It's a dime-sized silicone chip that "injects genetic code into skin cells, turning those skin cells into other types of cells required for treating diseased conditions," according to a release.

In lab tests, one touch of TNT completely repaired injured legs of miceoverthree weeks by turning skin cells into vascular cells.

And, it not only works on skin cells, it can restoreany type of tissue,Chandan Sen, director of the Center for Regenerative Medicine and Cell-Based Therapies, said. For example, the technology restored brain function in a mouse who suffered a stroke by growing brain cells on its skin.

This is a breakthrough technology, because it's the first time cells have been reprogrammed in a live body. Current cell therapy methods are high risk, like those that introduce a virus, and include multiple steps, a new study published in Nature Nanotechnology points out.There are no known side effects to TNT and treatment is less than a second, Sen said.

This technology does not require a laboratory or hospital and can actually be executed in the field," Sen said."Its less than 100 grams to carry and will have a long shelf life.

It is awaiting FDA approval, but Sen, who has been working on thisfor four years,expects TNT will be tested on humans within the year. He says he'stalking with Walter Reed National Medical Center now.

"We are proposing the use of skin as an agricultural land where you can essentially grow any cell of interest," Sen said.

Follow Ashley May on Twitter: @AshleyMayTweets

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New device can heal with a single touch, and even repair brain injuries - USA TODAY

Off-the-shelf T cell therapies for multiple myeloma – Medical Xpress

August 9, 2017

Although a source of much hope among 'multiple myeloma' (MM) patients, adoptive T cell therapies are still held back by expensive, lengthy, individual-tailored approaches. However, an EU-funded project is aiming to shake things up with off-the shelf solutions of its own.

There are currently three main approaches for obtaining therapeutic T cells: the isolation, expansion and reinfusion of tumour-infiltrating lymphocytes (TILs); the ex vivo generation and expansion of tumour antigen-specific T cell lines; and the genetic engineering of autologous T cells with tumour antigen-specific T cell receptors (TCRs) or chimeric antigen receptors (CARs). But whilst the feasibility and effectiveness of these approaches have all been proven in clinical settings, all these approaches have to be tailored to the patient before they can be applied.

With this in mind, the CARIPSCTCELLS (Generation of safe and efficient, off-the-shelf, chimeric antigen receptor (CAR)-engineered T cells for broad application) project has developed technology that will enable in vitro, unlimited, safe and broadly applicable T cells targeting MM. Dr Maria Themeli, coordinator of the project, discusses its results.

Why are T cell therapies so rarely used?

Current strategies for obtaining therapeutic T cells have limitations. Their use is restricted to specialised institutes and specific patient populations. The isolation and ex vivo manipulation of autologous cells require expensive specialised equipment, good manufacturing practice (GMP) facilities and trained personnel. In many cases, the autologous T cell isolation and expansion would be problematic or impossible, for instance in immunosuppressed patients after chemotherapy or immune-deficient patients presenting malignancies.

Moreover, the production of autologous therapeutic cancer-specific T cells requires processing times which can be critical for the patient's health. Sometimes the patient dies before receiving the therapy. This all makes the production of therapeutic T cells an expensive process, which is difficult to be broadly applied.

How did your project aim to solve these problems? How did such solutions come about?

We thought that the development of broadly applicable cellular therapeutics, which have been manufactured, functionally validated and banked in advance, and can be applied beyond histocompatible Human leukocyte antigen (HLA) barriers, would improve the consistency and availability while reducing the cost of adoptive T cell therapy. With this goal in mind, we explored the feasibility of a novel strategy for generating unlimited, 'off-the-shelf', safe, antigen-specific T lymphocytes with optimised features.

We propose the use of induced pluripotent stem cells (iPSC) as a source of T lymphocytes. These cells can be cultured in the lab without limit and can be differentiated to T lymphocytes. In addition, they can be genetically manipulated easily, so that the final T cell product will possess specific desirable immunotherapeutic characteristics. For example, we can provide cancer antigen specificity through an artificial CAR and delete the expression of HLA molecules to make them histocompatible.

Why did you decide to focus specifically on MM?

The department of haematology at VUmc Amsterdam is one of the biggest European centres for MM patient care. What makes us so interested in this disease is that although there has been much progress in delaying the course of the disease, it still remains incurable. Therefore, we focus our research on finding novel, potentially curative therapies. To this end, we have developed and preclinically evaluated the use of CD38-targeting CAR-T cells for the treatment of MM.

How was the CRISPR/Cas9 system beneficial to your research?

The CRISPR/Cas9 technology has revolutionised the field of gene therapy over the last few years. With this technology, modifying the genome has become easier and safer, since it allows for highly specific gene editing. We use this system in order to genetically modify the cells in the iPSC stage and achieve specific optimised features when they differentiate into therapeutic T cells.

What would you say are the most important achievements of the project?

We have succeeded in generating genetically-modified iPSC, which give rise to broadly applicable 'off-the-shelf' T cells bearing an anti-myeloma CAR and eliciting anti-myeloma function without having histocompatibility restrictions.

What do you hope will be the long-term impact on MM treatment?

The development of 'off-the-shelf', applicable immunotherapeutic tools will lift immunotherapy from an individual basis and will allow the availability of controlled, validated and safe immunotherapeutics for a broad patient population.

MM is the second most common haematologic malignancy. Thus, a broadly applicable adoptive T cell immunotherapy would be of benefit for many patients. But most important, this project will lay the foundation for a new strategy for the broad application of iPSC-derived T cells, not only for targeting MM, but also for all CAR-based T cell therapies, since the results obtained from our studies could also be translated to other malignancies.

What are your follow-up plans, if any?

We aim to further pursue the goal of generating potent therapeutic T cells from iPSC. We will focus on further improving the therapeutic properties of the generated T cells from human iPSC by influencing and refining the in vitro differentiation mechanisms of phenotypic determination and by enhancing their persistence and effector function.

Explore further: What makes cancer gene therapy so groundbreaking?

More information: Project page: cordis.europa.eu/project/rcn/195614

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Off-the-shelf T cell therapies for multiple myeloma - Medical Xpress