Posts Tagged ‘stem cell’

by KERRY GRENS

In mice whose sense of smell has been disabled, a squirt of stem cells into the nose can restore olfaction, researchers report today (May 30) in Stem Cell Reports. The introduced “globose basal cells,” which are precursors to smell-sensing neurons, engrafted in the nose, matured into nerve cells, and sent axons to the mice’s olfactory bulbs in the brain.

“We were a bit surprised to find that cells could engraft fairly robustly with a simple nose drop delivery,” senior author Bradley Goldstein of the University of Miami Miller School of Medicine says in a press release. “To be potentially useful in humans, the main hurdle would be to identify a source of cells capable of engrafting, differentiating into olfactory neurons, and properly connecting to the olfactory bulbs of the brain. Further, one would need to define what clinical situations might be appropriate, rather than the animal model of acute olfactory injury.”

Goldstein and others have independently tried stem cell therapies to restore olfaction in animals previously, but he and his coauthors note in their study that it’s been difficult to determine whether the regained function came from the transplant or from endogenous repair stimulated by the experimental injury to induce a loss of olfaction. So his team developed a mouse whose resident globose basal cells only made nonfunctional neurons, and any restoration of smell would be attributed to the introduced cells.
The team developed the stem cell transplant by engineering mice that produce easily traceable green fluorescent cells. The researchers then harvested glowing green globose basal cells (as identified by the presence of a receptor called c-kit) and delivered them into the noses of the genetically engineered, smell-impaired mice. Four weeks later, the team observed the green cells in the nasal epithelium, with axons working their way into the olfactory bulb.

Behaviorally, the mice appeared to have a functioning sense of smell after the stem cell treatment. Unlike untreated animals, they avoided an area of an enclosure that had a bad smell to normal mice.

To move this technology into humans suffering from a loss of olfaction, more experiments in animals are necessary, says James Schwob, an olfactory researcher at Tufts University who has collaborated with Goldstein but was not involved in the latest study, in an interview with Gizmodo. “The challenge is going to be trying to [engraft analogous cells] in humans in a way . . . that [would] not make things worse.”

https://www.the-scientist.com/news-opinion/stem-cells-delivered-to-the-nose-restore-mices-ability-to-smell-65953

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Crohn’s disease is a long-term condition that causes inflammation of the lining of the digestive system, and results in diarrhoea, abdominal pain, extreme tiredness and other symptoms that significantly affect quality of life.

Current treatments include drugs to reduce inflammation but these have varying results, and surgery is often needed to remove the affected part of the bowel. In extreme cases, after multiple operations over the years, patients may require a final operation to divert the bowel from the anus to an opening in the stomach, called a stoma, where stools are collected in a pouch.

Chief investigator Professor James Lindsay from Queen Mary’s Blizard Institute and a consultant at Barts Health NHS Trust said: “Despite the introduction of new drugs, there are still many patients who don’t respond, or gradually lose response, to all available treatments. Although surgery with the formation of a stoma may be an option that allows patients to return to normal daily activities, it is not suitable in some and others may not want to consider this approach.

“We’re hoping that by completely resetting the patient’s immune system through a stem cell transplant, we might be able to radically alter the course of the disease. While it may not be a cure, it may allow some patients to finally respond to drugs which previously did not work.”

Helen Bartlett, a Crohn’s disease patient who had stem cell therapy at John Radcliffe Hospital, Oxford, said: “Living with Crohn’s is a daily struggle. You go to the toilet so often, you bleed a lot and it’s incredibly tiring. You also always need to be careful about where you go. I’ve had to get off trains before because there’s been no toilet, and I needed to go there and then.

“I’ve been in and out of hospital for the last twenty years, operation after operation, drug after drug, to try to beat this disease. It’s frustrating, it’s depressing and you just feel so low.

“When offered the stem cell transplant, it was a complete no brainer as I didn’t want to go through yet more failed operations. I cannot describe how much better I feel since the treatment. I still have problems and I’m always going to have problems, but I’m not in that constant pain.”

The use of stem cell transplants to wipe out and replace patients’ immune systems has recently been found to be successful in treating multiple sclerosis. This new trial will investigate whether a similar treatment could reduce gut inflammation and offer hope to people with Crohn’s disease.

In the trial, patients undergo chemotherapy and hormone treatment to mobilise their stem cells, which are then harvested from their blood. Further chemotherapy is then used to wipe out their faulty immune system. When the stem cells are re-introduced back into the body, they develop into new immune cells which give the patient a fresh immune system.

In theory, the new immune system will then no longer react adversely to the patient’s own gut to cause inflammation, and it will also not act on drug compounds to remove them from their gut before they have had a chance to work.

Professor Tom Walley, Director of the NIHR Evaluation, Trials and Studies programmes, which funded the trial, said: “Stem cell therapies are an important, active and growing area of research with great potential. There are early findings showing a role for stem cells in replacing damaged tissue. In Crohn’s disease this approach could offer real benefits for the clinical care and long term health of patients.”

The current clinical trial, called ‘ASTIClite’, is a follow up to the team’s 2015 ‘ASTIC’ trial, which investigated a similar stem cell therapy. Although the therapy in the original trial did not cure the disease, the team found that many patients did see benefit from the treatment, justifying a further clinical trial. There were also some serious side effects from the doses of drugs used, so this follow-up trial will be using a lower dose of the treatment to minimise risks due to toxicity.

Patients will be recruited to the trial through Barts Health NHS Trust, Cambridge University Hospitals NHS Foundation Trust, Guy’s & St Thomas’ NHS Foundation Trust, NHS Lothian, Nottingham University Hospitals NHS Trust, Oxford University Hospitals NHS Foundation Trust, Royal Liverpool and Broadgreen University Hospital NHS Trust and Sheffield Teaching Hospitals NHS Foundation Trust.

The trial will involve academics from the University of Manchester, University of Nottingham, University of Sheffield, Nottingham Trent University, University of Edinburgh, University of Oxford, King’s College London, as well as Queen Mary University of London.

The study was funded by a Medical Research Council and NIHR partnership created to support the evaluation of interventions with potential to make a step-change in the promotion of health, treatment of disease and improvement of rehabilitation or long-term care.

https://www.qmul.ac.uk/media/news/2018/smd/stem-cell-transplants-to-be-used-in-treating-crohns-disease.html


Holly Drewry, 25, of Sheffield, was wheelchair bound after the birth of her daughter Isla, now two.

A pioneering new stem cell treatment is reversing and then halting the potentially crippling effects of multiple sclerosis.

Patients embarking on a ground-breaking trial of the new treatment have found they can walk again and that the disease even appears to be stopped in its tracks.

Holly Drewry, 25, from Sheffield, was wheelchair bound after the birth of her daughter Isla, now two. But Miss Drewry claims the new treatment has transformed her life.

She told the BBC’s Panorama programme: “I couldn’t walk steadily. I couldn’t trust myself holding her (Isla) in case I fell. Being a new mum I wanted to do it all properly but my MS was stopping me from doing it.

“It is scary because you think, when is it going to end?”

The treatment is being carried out at Royal Hallamshire Hospital in Sheffield and Kings College Hospital, London and involves use a high dose of chemotherapy to knock out the immune system before rebuilding it with stem cells taken from the patient’s own blood.

Miss Drewry had the treatment in Sheffield. She said: “I started seeing changes within days of the stem cells being put in.

“I walked out of the hospital. I walked into my house and hugged Isla. I cried and cried. It was a bit overwhelming. It was a miracle.”

Her treatment has now been reviewed and her condition found to have been dramatically halted. She will need to be monitored for years but the hope is that her transplant will be a permanent fix.

She is now planning to get married.

For other patients, the results have been equally dramatic. Steven Storey was a marathon runner and triathlete before he was struck down with the disease and left completely paralysed: “I couldn’t flicker a muscle,” he said.

But within nine days of the treatment he could move his toe and after 10 months managed a mile-long swim in the Lake District. He has also managed to ride a bike and walk again.

“It was great. I felt I was back,” he said.

Mr Storey celebrated his first transplant birthday with his daughters. His treatment has been reviewed and, like Miss Drewry, there was no evidence of active disease.

The treatment – which effectively ‘reboots’ the immune systems – is the first to reverse the symptoms of MS, which has no cure, and affects around 100,000 people in Britain.

Stem cells are so effective because they can become any cell in the body based on their environment.

Although it is unclear what causes MS, some doctors believe that it is the immune system itself which attacks the brain and spinal cord, leading to inflammation and pain, disability and in severe cases, death.

Professor Basil Sharrack, a consultant neurologist at Sheffield Teaching Hospitals NHS Foundation Trust, said: “Since we started treating patients three years ago, some of the results we have seen have been miraculous.

“This is not a word I would use lightly, but we have seen profound neurological improvements.”

During the treatment, the patient’s stem cells are harvested and stored. Then doctors use aggressive drugs which are usually given to cancer patients to completely destroy the immune system.

The harvested stem cells are then infused back into the body where they start to grow new red and white blood cells within just two weeks.

Within a month the immune system is back up and running fully and that is when patients begin to notice that they are recovering.

However specialists warn that patients need to be fit to benefit from the new treatment.

The research has been published in the Journal of the American Medical Association.

http://www.telegraph.co.uk/news/health/news/12104774/Miraculous-results-from-new-MS-treatment.html

Thanks to Steve Weihing for bringing this to the It’s Interesting community.