New research provides further evidence of autologous hematopoietic stem cell transplantation as an effective treatment for multiple sclerosis, after finding the procedure halted disease progression for 5 years in almost half of patients.

Lead study author Dr. Paolo Muraro, of the Department of Medicine at Imperial College London in the United Kingdom, and colleagues recently reported their findings in JAMA Neurology.

The results come just a fortnight after another study revealed the success of a similar treatment in a small group of patients with relapsing-remitting multiple sclerosis (RRMS).

However, Dr. Muraro and team warn that further trials are needed to determine the efficacy and safety of autologous hematopoietic stem cell transplantation (AHSCT), after a small number of patients died within 100 days of treatment.

In AHSCT, a patient's own stem cells are harvested. The patient is then subject to high-dose chemotherapy to eliminate any diseased cells.

Next, the harvested stem cells are returned to the patient's bloodstream, with the aim of restarting normal blood cell production. In simple terms, AHSCT "resets" the immune system.

"We previously knew this treatment reboots or resets the immune system - and that it carried risks - but we didn't know how long the benefits lasted," notes Dr. Muraro.

For their study, the researchers assessed data from 25 treatment centers across 13 countries, identifying 281 patients with multiple sclerosis (MS) who underwent AHSCT between 1995-2006. Of these patients, 78 percent had a progressive form of MS.

Using the Expanded Disability Status Scale (EDSS), the team evaluated patients' progression-free survival at 5 years after treatment and any improvements in MS symptoms.

An EDSS score of zero represents no disability, seven represents the use of a wheelchair, while 10 represents death from MS. At the beginning of the study, patients had an average EDSS score of 6.5.

Overall, the researchers found that 46 percent of patients experienced no disease progression in the 5 years after treatment.

Patients with RRMS - characterized by inflammatory attacks, or "flare-ups," followed by periods of remission - had the best outcomes, with 73 percent experiencing no worsening of symptoms in the 5 years after AHSCT.

Additionally, patients experienced small improvements in MS symptoms after AHSCT. Patients with progressive MS saw their EDSS score rise by 0.14 a year after treatment, while patients with RRMS experienced a 0.76 increase in their EDSS score.

Patients with a younger age, few immunotherapies prior to AHSCT, and a lower EDSS score at study baseline also showed better outcomes with AHSCT.

While these findings show promise for the use of AHSCT for patients with MS, the team notes that there were eight deaths in the 100 days after AHSCT, which were thought to have been treatment related.

AHSCT involves aggressive chemotherapy, which can severely weaken the immune system and increase susceptibility to infection.

"In this study, which is the largest long-term follow-up study of this procedure, we've shown we can 'freeze' a patient's disease - and stop it from becoming worse, for up to 5 years.

However, we must take into account that the treatment carries a small risk of death, and this is a disease that is not immediately life-threatening."

Dr. Paolo Muraro

Dr. Muraro notes that, importantly, this study did not include a group of MS patients who did not receive treatment, further highlighting the need for more studies assessing the safety and efficacy of AHSCT.

"We urgently need more effective treatments for this devastating condition, and so a large randomized controlled trial of this treatment should be the next step," he adds.

Read about a study that links vitamin D level at birth to the risk of MS.

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Multiple sclerosis: Stem cell transplantation may halt disease progression - Medical News Today

1. Combining tumor-specific T cells and pathogen-based immune stimulation, reenergized adoptive cell transfer (ReACT) targeted and eradicated tumor cells in mice.

2. ReACT led to increased migration of activated T cells to the tumors, a metric that correlated with decreased tumor size.

Evidence Rating Level: 2 (Good)

Study Rundown: Because cancer cells can evade being targeted by the bodys immune system, therapies have been developed to alter the tumors immune microenvironment. One therapy, adoptive cell transfer (ACT), involves engineering T cells to target cells that express tumor-associated antigens (TAAs). Although this therapy has potential, the tumor microenvironment causes inhibition of T cell function, preventing the therapys long-term efficacy. Another approach has been to use pathogens that express TAAs to stimulate the immune system. However, since some tumor cells have altered TAAs, they evade being targeted. In this study, these two approaches were combined into a therapy named ReACT: T cells were engineered to target a TAA as well as a bacterial antigen, and the cells were administered along with a bacterial adjuvant.

When treated with ReACT, a majority of mice with implanted melanoma cells experienced tumor eradication. An increased frequency of T cells in the tumor environment correlated with decreased tumor size. In addition, biomarker levels indicated effective T cell migration and activation. A polyclonal form of ReACT was also tested in a mouse model of melanoma; following tumor eradication in these mice, more tumor cells were introduced but failed to survive, demonstrating an immunological memory response induced by this therapy.

This study demonstrated a new approach for a safer and more efficacious cancer immunotherapy. Future studies will need to more closely mimic a clinical model and provide specific data describing the mechanism of T cell function in this therapy.

Click to read the study in PNAS

Relevant Reading: Cancer Immunotherapy: Strategies for Personalization and Combinatorial Approaches

In-Depth [animal study]: The researchers obtained CD8 T cells that expressed a T cell receptor (TCR) that recognizes a TAA specific to murine melanoma cells. These T cells were then engineered to express a TCR that recognizes the antigen ovalbumin (OVA). In mice with melanoma tumors, this treatment was only effective when the T cells were administered in conjunction with OVA conjugated to Listeria (LM-OVA), a model organism used for pathogen-based cancer vaccines. Seven out of 10 mice experienced complete tumor cell eradication (p<0.001). Neither the engineered T cells alone nor the LM-OVA alone was sufficient to produce significant tumor regression.

Next, the properties and functions of the ReACT T cells were analyzed. The CD8 T cells were present at a higher frequency in the ReACT-treated mice and this value negatively correlated to tumor size, with an r-value of -0.699. These T cells had an activated phenotype, with an increased expression of CD44 and other transcription factors as well as a decreased expression of inhibitory receptors such as CTLA-4. These T cells also had a high expression of CXCR3, a chemokine receptor involved in migration to tumor cells.

Finally, polyclonal ReACT was tested in mice with melanoma tumors. Tumor-specific CD8 T cells were generated by stimulating them with dendritic cells presenting a pool of TAAs; the cells were additionally engineered to express the OVA TCR, and administered to mice along with LM-OVA. Eleven out of 16 mice experienced complete tumor eradication. These mice were then reintroduced to the same melanoma cell line and were resistant to tumor relapse, demonstrating the establishment of an immunological memory response.

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2 Minute Medicines The Classics in Medicine: Summaries of the Landmark Trials is available now in paperback and e-book editions.

This text summarizes the key trials in:General Medicine and Chronic Disease, Cardiology, Critical and Emergent Care, Endocrinology, Gastroenterology, Hematology and Oncology, Imaging, Infectious Disease, Nephrology, Neurology, Pediatrics, Psychiatry, Pulmonology, and Surgery.

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This article was originally published on The Conversation. Read the original article.

Most of the research behind new medical advances is carried out using either animal tissues or cancer cells. Both tools have their problems: results from animals and humans do not always match up and cancer cells grown for years in laboratories often do not mimic the tissues they originally came from very well. Bridging the gap between whole animals and simple cells can be a challenge during the development of new treatments, but this is beginning to change since scientists have learned how to grow organoids.

Organoids are clusters of cells that organize themselves into mini versions of our organs. They are grown from stem cells, and their use has only become possible with the discovery of the precise conditions needed to keep stem cells alive outside the body. Organoids were first made from intestines but have since been made using many other tissues, including liver, breast and even brain cells. This will allow scientists to better study the development and diseases of these organs.

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An engineer from CNRS (French Reseach Institut Center) introduces embryonic stem cells in a mouse embryo to set a genetically modified line, Marseille, France, February 9, 2012. Organoidslab-grown miniature versions of organsare proving to be a game changer in the field of medical research. Anne-Christine Poujoulat/AFP/Getty Images

They are grown in a gel that allows them to develop three-dimensionally, so they mimic the architecture of our organs much more realistically than a simple layer of cells. Stem cells from the intestine multiply to form a ball, in which the hollow centeris like the space inside the intestine. The surface of these balls then buds outwardat various points to form pocket-like extensions. This is similar to the intensely folded surface of the gut wall.

Organoids have several advantages over existing approaches. Stem cells are taken from animals or patients and continually multiply so the organoids can be maintained for months. They provide an unlimited supply of material for study, meaning fewer animal studies are required. Making organoids from patients also raises intriguing possibilities for personalized medicine.

In traditional cell cultures every cell is identical but stem cells can form many different cell types, so organoids contain a much more realistic mixture of cells. For example, M cells are specialized cells in the gut wall that act as surveillance posts, capturing bacteria from the gut and showing them to the immune system so it can monitor for danger. Some harmful bacteria exploit this to invade the gut wall. It was previously tricky to grow M cells in the lab for study, but they can be grown in organoids. When added to organoids, Salmonella, a bacterium that causes food poisoning, infected M cells more often than other cell types, suggesting this may be a route of infection in humans.

Some common disease-causing bacteria are surprisingly difficult to grow in the lab, making them hard to study. Clostridium difficile causes numerous cases of diarrhoea every year, a serious condition in frail patients. It has been difficult to grow C. difficile because it requires conditions without oxygen, but researchers in the U.S. have shown that the bug can survive inside intestinal organoids. Bacteria were injected into the centerof intestinal organoids and produced a toxin that made the organoid wall leakier, damaging its ability to act as a barrier.

Organoids made from patient biopsies are allowing us to investigate differences between individuals. Patients with cystic fibrosis show varied responses to treatments. One group of researchers grew organoids from patient biopsies and tested their response to different combinations of drugs. In the future this may be used to quickly find the best treatment for each individual.

Tumors also vary hugely between individuals. Dutch researchers grew organoids from patients with colorectal tumors and identified genetic changes that had occurred in the tumour cells compared to the patients healthy tissue. They were then able to see how these altered the way the cells behaved. They tested anti-cancer drugs on the organoids and could tell which drugs did and did not kill the tumor cells.

Imagine if organoids were routinely made from tumor biopsies and used to identify the best chemotherapy combination for each patient. This is certainly plausible, but the process will first need to be made quicker and cheaper.

All this makes organoids an exciting new tool for researchers. Most work currently focuses on the stomach and intestine, but the technique is quickly expanding to other tissues, such as liver, breast and brain. Organoids will transform the way we conduct medical research, from basic understanding to drug development and personalized therapies. Expect to hear much more about them in the future.

Louise ThompsonisPhD candidate in Molecular and Cellular Physiology at theUniversity of Liverpool.

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Here's Why Organoids Are a Game Changer in Medical Research - Newsweek

JACKSONVILLE, Fla. As a boy growing up in Kano, Nigeria, Dr. Abba Zubair dreamed of going to space.

On Sunday, his work hitched a ride with a private rocket blasting off from NASA's Kennedy Space Center in Cape Canaveral, Fla., on a trip to the International Space Station.

Dr. Zubair, an associate professor of laboratory medicine and pathology at the Mayo Clinic's Florida campus, prepared a science package involving stem cells as part of a resupply mission to the ISS aboard a SpaceX Falcon 9 rocket.

"It was my first rocket launch view," said Dr. Zubair, who was on hand to watch and listen to the deafening sound as his experiment rode into space. "It was incredible."

The stem cells -- specialized cells derived from bone marrow come from Dr. Zubair's lab. Dr. Zubair, according to a report from the Mayo Clinic, specializes in cellular treatments for disease and regenerative medicine. He hopes to find out how the stem cells hold up in space and if they can be more quickly produced in microgravity.

More specifically, Zubair said, he is hoping the research can help in treatment of patients who have suffered a stroke-related brain injury.

"Stem cells are known to reduce inflammation," he said in a press release. "We've shown that an infusion of stem cells at the site of stroke improves the inflammation and also secretes factors for the regeneration of neurons and blood vessels."

The problem with such a treatment and studying the treatment is generating enough stem cells for the job. Based on current regenerative medicine studies, patients need at least 100 million stem cells for an effective dose. However, reproducing stem cells can be time consuming since the cells naturally limit their numbers.

"Scalability is a big issue," Dr. Zubair said. "I've been interested in a faster way to make them divide."

And on earth, everything is impacted by gravity, from how high we grow to our bone size and other physiological traits. "So, how can we use the effect of gravity to impact how the cells divide?" he asked.

Experiments that simulate stem cell growth in microgravity, thus far, have shown cells do grow more quickly than experimental controls, he said. So he began working toward getting an experiment into space. The experiment needed to be designed so the crew onboard the space station could run the experiment with some simple training, and Dr. Zubair will be able to watch the experiment in real time via a video connection. "We'll get some data as early as next week," he said.

If all goes well, growing stem cells in space something Dr. Zubair admits sounds like a dream of the distant future might become a reality more quickly than many people think.

"There are some companies interested in floating labs," he said. "I think the future is bright. There are a lot of possibilities in the area of regenerative medicine."

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Mayo doc's stem cell experiment blasts into space - Post-Bulletin

February 20, 2017 by Dov Smith

Non-Hodgkin lymphomas (NHL), tumors which may originate from B or T lymphocytes, account for approximately 3% of the worldwide cancer burden. Most epidemiological studies of NHL have been carried out in North American and European populations, with a few focusing on East Asian populations. Very few epidemiological studies have been conducted on B-cell non-Hodgkin lymphoma (B-NHL) in Middle Eastern populations.

Since Israelis and Palestinians represent genetically and culturally diverse populations living in geographic proximity, research analyzing their risk factors can enrich our understanding of genes and environment in the causation of lymphoma. Despite sharing the same ecosystem, the populations differ in terms of lifestyle, health behaviors and medical systems. Yet both populations report high incidences of NHL, which represents the fifth most common malignancy in Israel and the eighth most common malignancy among West Bank Palestinians. (As of 2012, Israel also ranked first in the world in NHL incidence rates.)

Now, Israeli and Palestinian researchers, led by Prof. Ora Paltiel, Director of the Hebrew University-Hadassah Braun School of Public Health and Community Medicine, and a Senior Physician in Hadassah's Hematology Department, have conducted a large scale epidemiological study examining risk factors for B-NHL and its subtypes in these two populations.

Recruiting from both the Palestinian Arab and Israeli Jewish populations, the researchers looked at medical history, environmental and lifestyle factors among 823 people with B-cell non-Hodgkin lymphoma (B-NHL) and 808 healthy controls. Using data from questionnaires, pathology review, serology and genotyping, they uncovered some risk factors common to both populations and other factors unique to each population.

The data, reported in the peer-reviewed journal PLOS ONE, showed that in both populations, overall B-NHL was associated with recreational sun exposure, black hair-dye use, a history of hospitalization for infection, and having a first-degree relative with a blood cancer. An inverse association was noted with alcohol use. Some exposures, including smoking and greater-than-monthly indoor pesticide use, were associated with specific subtypes of B-NHL.

The data also pointed to differences between the populations. Among Palestinian Arabs only, risk factors included gardening and a history of herpes, mononucleosis, rubella, or blood transfusion, while these factors were not identified in the Israeli Jewish population. In contrast, risk factors that applied to Israeli Jews only included growing fruits and vegetables, and self-reported autoimmune diseases.

The researchers concluded that differences in the observed risk factors by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by lymphoma subtypes infer specific causal factors for different types of the disease. These findings require further investigation as to their mechanisms.

The fact that risk factors operate differently in different ethnic groups raises the possibility of gene-environment interactions, that is, that environmental exposures act differently in individuals of different genetic backgrounds. But this divergence may reflect differences in diet, cultural habits, socioeconomic, environmental and housing conditions, medical services, exposure to infections in early life or other factors.

This study reflects a unique joint scientific effort involving Israeli and Palestinian investigators, and demonstrates the importance of cooperative research even in politically uncertain climates. Cancer epidemiology will be enriched through the broadening of analytic research to include under-studied populations from a variety of ethnicities and geographic regions.

"Apart from the scientific contribution that this research provides in terms of understanding risk factors for NHL, the study entails an important research cooperation among many institutions. The study provided opportunities for training Palestinian and Israeli researchers, and will provide for intellectual interaction for years to come. The data collected will also provide a research platform for the future study of lymphoma. Epidemiologic research has the potential to improve and preserve human health, and it can also serve as a bridge to dialogue among nations," said Prof. Ora Paltiel, Director of the Hebrew University-Hadassah Braun School of Public Health and Community Medicine, and a Senior Physician in Hadassah's Hematology Department.

Explore further: Israeli lifestyle and environment may pose exceptional risks for Hodgkin's lymphoma

More information: Geffen Kleinstern et al. Ethnic variation in medical and lifestyle risk factors for B cell non-Hodgkin lymphoma: A case-control study among Israelis and Palestinians, PLOS ONE (2017). DOI: 10.1371/journal.pone.0171709

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Top Stem Cell in Las Vegas and Henderson NV (844) GET-STEM

Las Vegas, Nevada (PRWEB) February 20, 2017

R3 Stem Cell is now offering regenerative medicine treatment in Las Vegas and Henderson Nevada. Treatments have helped many patients avoid surgery and improve their lives dramatically. R3 has partnered with Dynamic Stem Cell Therapy to offer treatment for all types of conditions. Call (844) GET-STEM for more information and scheduling.

Regenerative medicine therapy with stem cells has become mainstream, and the pioneers at Dynamic Stem Cell Therapy are experts. The conditions treated include arthritis, tendonitis, sports injuries, ligament injuries along with a host of systemic issues such as COPD, CHF, Lupus, Rheumatoid Arthritis, Crohns Disease, Diabetes and many more.

The Las Vegas stem cell center uses the patients adipose tissue, and concentrates the stem cells in a same day treatment. The treatment is offered either as an injection or an infusion, depending on the need.

The therapy works great for helping patients avoid the need for potentially risky surgery, such as joint replacement or tendonitis surgery. Not only does the procedure include stem cells, but also growth factors along with other healing agents.

Along with the adipose stem cell therapy, the Las Vegas stem cell doctors utilize platelet rich plasma therapy, known as PRP therapy for short. The combination of the two augment the capability of repair.

In addition to bone and joint conditions along with organ issues, Dynamic offers cosmetic procedures as well. This includes the Vampire facelift along with hair restoration that works great from platelet rich plasma therapy.

Over 85% of patients benefit from the regenerative medicine procedures. Call (844) GET-STEM for more information and scheduling with the top stem cell therapy in Las Vegas.

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