Chinese team tests lung treatment that may be first to reverse COPD damage – South China Morning Post

But through preclinical studies in mice and monkeys, the team and other scientists have found that resident progenitor lung cells capable of differentiating into multiple types of lung cells had a capacity for regeneration.

Healthy progenitor cells are often deficient in patients with COPD, however even those with the most severe stages of the disease still have healthy cells that can be isolated and used in personalised treatments.

These cells could be used as a Band-Aid for the lungs which could repair tissues in the airways and even deeper into the alveoli, the paper said.

Stem cell and progenitor cell-based regenerative medicine may be the biggest, if not the only, hope to cure COPD, Zuo Wei, study author and a professor at the Tongji University School of Medicine, said during a presentation at the European Respiratory Society International Congress last year.

In a phase 1 clinical trial of their treatment, the team collected healthy progenitor lung cells, called P63+, from the patients lungs via a bronchoscopy. The cells were then cultured in a lab for three to five weeks to make millions of cell clones.

Once the cells had multiplied, they were transplanted back into the patients via another bronchoscopy. A final evaluation of the patients was conducted six months after treatment.

The 17 patients with varying stages of COPD who received the treatment had no serious adverse side effects, and those that did occur were primarily a result of the bronchoscopy procedure, the team wrote.

New Chinese drug shows record treatment success against deadly lung cancer type

The scientists also did not observe any signs of tumour formation in the patients six months after transplant.

When evaluating the lungs ability to diffuse carbon monoxide which is used as a lung function test for COPD the scientists found that the study group had improved diffusion capacity compared to the baseline and control patients.

During a six-minute walking test, the study group was able to walk around 30 metres further after the treatment, which was a clinically meaningful improvement in exercise capacity, the paper said.

Surveys of the trial participants also suggested that most patients in the intervention group had an improved quality of life after treatment, the team wrote.

03:05

Heavy smog descends on India, leaving residents struggling to breathe

Heavy smog descends on India, leaving residents struggling to breathe

We found that P63+ progenitor cell transplantation not only improved the lung function of patients with COPD, but also relieved their symptoms, such as shortness of breath, loss of exercise ability and persistent coughing, Zuo said.

The improvement in gas diffusion capacity and walking distance in the treated patients supports further clinical studies of P63+ progenitor cells for the treatment of COPD Melissa Norton, senior editor of the journal, said in an editors summary of the paper.

Their symptoms will become worse: climate change threat to lung patients

The authors said the first phase of the clinical trial proved their treatment was safe and well tolerated, but it was limited to a small sample size comprising only men, so it was not suitable to determine efficacy yet.

To address this, the team is conducting an ongoing phase 2 clinical trial with a larger study group and follow-up time that looks at more indicators of lung function.

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Chinese team tests lung treatment that may be first to reverse COPD damage - South China Morning Post

Stopping the awakening of sleeping Acute Myeloid Leukaemia stem cells to prevent disease relapse – University of Birmingham

New study provides clues to why leukaemic stem cells not harmed by chemotherapy begin to grow and produce AML cells after treatment.

Published 15 February 2024

The mystery of why myeloid leukaemias start to grow again after chemotherapy has killed the bulk of malignant cells, and how growth may be blocked by repurposed drugs, has potentially been solved through new research.

The bone marrow of AML patients contains a rare population of leukaemic stem cells (LSCs) that do not grow and therefore are not killed by chemotherapy. However, after treatment, these cells start to grow and produce AML cells, but it was unclear what kick-starts this process.

In a new study published in Nature Communications, researchers from the University of Birmingham, Newcastle University and the Princess Maxima Centre of Pediatric oncology studied single cells from patients with t(8;21) Acute Myeloid Leukaemia, a specific type of blood cancer, to investigate what made the rare LSCs grow.

Leukaemic stem cells normally seem asleep which is why they are not killed by chemotherapy, but we reasoned that something must trigger them to start growing in order for the leukaemia to come back.

Professor Constanze Bonifer from the Institute of Cancer and Genomic Sciences at the University of Birmingham who led the study said:

"Leukaemic stem cells normally seem asleep which is why they are not killed by chemotherapy, but we reasoned that something must trigger them to start growing in order for the leukaemia to come back.

These cells are very rare and difficult to study but by examining gene expression in single LSCs we found genes being expressed that encode for growth regulators normally not present in myeloid cells. Both cell types are found in the bone marrow alongside the AML cells, but healthy stem cells do not respond to their signals. By aberrantly upregulating these growth regulators, leukaemic stem cells now can respond to growth factors that are present in the body and tell them to grow."

The growth regulators, identified in this study were KDR, the receptor for VEGF signalling which is normally only expressed in blood vessels and the IL-5 receptor which is normally only expressed on eosinophils. Moreover, VEGFA, the growth factor binding to KDR, was also expressed by the leukaemia meaning it could trigger its own growth. Following identification of these receptors, the researchers confirmed that by activating them in the laboratory they were able to trigger stem cells growth. Importantly, they also showed that growth could be blocked in a dish and in mice by repurposing drugs against VEGF (Avastin, approved for various solid tumours including colorectal cancer) and IL-5 signalling (Fasenra, approved for eosinophilic asthma).

Professor Olaf Heidenreich from Newcastle University and the Princess Maxima Centre of Pediatric Oncology says:

An exciting result from these studies is the fact that the expression of these receptors is specific to this particular type of leukemia. They are expressed as a result of the presence of a specific disease-causing mutation giving rise to the onco-fusion protein RUNX1::ETO which reprograms the gene regulatory network that defines how a cell responds to outside growth signals.

"This work highlights the power of single cell analysis for digging deep into what regulates the growth of AML cells. It also highlights the fact that AML sub-types may have to be treated as a separate entities.

The first author of the study, Dr Sophie Kellaway who is now continuing this research at the University of Nottingham says:

"We were very excited to find not one but two new, and potentially druggable targets to prevent relapse in these patients. Being told your cancer has come back is devastating news and we want to prevent this happening. Unfortunately, as these receptors were so specific this would only work for t(8;21) acute myeloid leukaemia and is not a magic bullet.

"However, inspection of other single cell data from different leukaemia sub-types show that other growth regulatory pathways are upregulated in their stem cell population as well. We are now hoping to find those that can be hit in other types of AML".

Dr Suzanne Rix, from Blood Cancer UK, said: Blood cancer is the UKs third biggest cancer killer and acute myeloid leukaemia is a particularly aggressive form of blood cancer that can come back even after initial treatments have been successful.

"This research uncovers why one specific type of acute myeloid leukaemia can return, and could lead to the development of new treatments with the potential to stop the cancer coming back, giving new hope to people affected by this specific form of leukaemia. However, further work is needed to see whether a similar approach could be taken for other forms of acute myeloid leukaemia and more broadly much more research is desperately needed to develop effective, kinder treatments for all blood cancers.

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Stopping the awakening of sleeping Acute Myeloid Leukaemia stem cells to prevent disease relapse - University of Birmingham

Oldest Patient ‘Cured’ of HIV Still in Remission 5 Years After Transplant for AML – Medpage Today

A 68-year-old man with HIV-1 who underwent hematopoietic cell transplant (HCT) for acute myelogenous leukemia 5 years ago has been free of HIV infection for 35 months after stopping antiretroviral treatment (ART), according to a case report.

The patient received an HCT from a donor with the rare delta-32 mutation, which causes a CCR5 deletion (CCR5-32/32) and has been associated with resistance to HIV-1 infection, Jana Dickter, MD, of City of Hope National Medical Center in Duarte, California, and colleagues wrote in the New England Journal of Medicine.

"He was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions," Dickter told MedPage Today. "He also had been living with HIV the longest of any of the patients to date -- for more than 31 years -- prior to transplant."

"His case opens up the possibilities for other older persons living with HIV and a blood cancer to receive a transplant and achieve remission for both diseases if a donor with this rare genetic mutation [delta-32] can be identified," she noted.

The patient, known as the City of Hope patient, is unique among a handful of other patients who achieved HIV remission after stem cell transplants for hematologic cancers, not only because he was older and more frail, but because he also received reduced-intensity conditioning before transplant, Dickter said. Other HCT recipients who achieved prolonged HIV remission had undergone intensive immunotherapy with T-cell depletion prior to transplant.

Prior to HCT, the City of Hope patient had been on ART since 1997 and had no detectable HIV-1 RNA at the time of transplant, the authors reported. ART was halted 35 months after HCT, per current recommendations. Since then, his CD4 counts have ranged from 356 to 1,271 cells per microliter, and HIV-1 RNA and cellular DNA and RNA have remained undetectable, the authors wrote. HIV DNA in peripheral blood mononuclear cells was "mostly undetectable" in those cells and also in gut tissue after HCT. Researchers also tested for intact proviral DNA after HCT and found a more than 2-log reduction in total proviruses. No intact or total proviruses were detected after ART interruption.

His blood, bone marrow, and reservoir sites converted to full chimerism with the CCR5-32/32 donor cells, the authors concluded. At the time of the report, the patient remains in remission from HIV and his acute leukemia, while receiving topical treatment for oral graft-versus-host disease.

The current evidence is nevertheless not enough to support wider use of stem cell transplantation to cure HIV, cautioned Joel Blankson, MD, PhD, of Johns Hopkins Medicine in Baltimore.

"The problem is we don't know what the denominator is. We don't know how many times it's been tried," Blankson commented to MedPage Today. "But it is very encouraging that we've gone past 'N is equal to one' to the point where we now have 'N is equal to five'," referring to the five patients known to be in HIV remission after a bone marrow transplant -- the Berlin, London, Dsseldorf, New York, and City of Hope patients.

Blankson pointed to 2019 data from IciStem, a European collaborative investigating the potential for HIV cure in HIV-infected patients requiring stem cell transplantation for hematological disorders. At that time, 39 patients registered with IciStem had received transplants, but there were only two possible examples of a cure in that group.

In July 2023, researchers reported that a sixth person, the Geneva patient, had been in remission for 20 months and, remarkably, that person's donor did not have the protective delta-32 mutation.

Blankson said he sometimes encounters patients with HIV who ask about stem cell transplants to achieve HIV remission. In addition to emphasizing the lack of data, he also stresses that "we don't have a clear estimate of the mortality rate" for the procedure.

"And, it's going to be very expensive," he noted. "It's never going to be a high throughput procedure where lots of people can get this, I don't think."

Katherine Kahn is a staff writer at MedPage Today, covering the infectious diseases beat. She has been a medical writer for over 15 years.

Disclosures

Dickter reported no conflicts of interest. Co-authors reported ties to industry.

Blankson disclosed no conflicts of interest.

Primary Source

New England Journal of Medicine

Source Reference: Dickter JK, et al "HIV-1 remission after allogeneic hematopoietic-cell transplantation" N Engl J Med 2024; DOI: 10.1056/NEJMc2312556.

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Oldest Patient 'Cured' of HIV Still in Remission 5 Years After Transplant for AML - Medpage Today

The untapped potential of stem cells in menstrual blood – Gavi, the Vaccine Alliance

Roughly 20 years ago, a biologist named Caroline Gargett went in search of some remarkable cells in tissue that had been removed during hysterectomy surgeries. The cells came from the endometrium, which lines the inside of the uterus. When Gargett cultured the cells in a petri dish, they looked like round clumps surrounded by a clear, pink medium. But examining them with a microscope, she saw what she was looking for two kinds of cells, one flat and roundish, the other elongated and tapered, with whisker-like protrusions.

Gargett strongly suspected that the cells were adultstem cells rare, self-renewing cells, some of which can give rise to many different types of tissues. She and other researchers had long hypothesized that the endometrium contained stem cells, given its remarkable capacity to regrow itself each month. The tissue, which provides a site for an embryo to implant during pregnancy and is shed during menstruation,undergoes roughly 400 roundsof shedding and regrowth before a woman reaches menopause. But although scientists had isolated adult stem cells from many other regenerating tissues including bone marrow, the heart, and muscle "no one had identified adult stem cells in endometrium," Gargett says.

Such cells are highly valued for their potential to repair damaged tissue and treat diseases such as cancer and heart failure. But they exist in low numbers throughout the body, and can be tricky to obtain, requiring surgical biopsy, or extracting bone marrow with a needle. The prospect of a previously untapped source of adult stem cells was thrilling on its own, says Gargett. And it also raised the exciting possibility of a new approach to long-neglected women's health conditions such as endometriosis.

Before she could claim that the cells were truly stem cells, Gargett and her team at Monash University in Australia had to put them through a series of rigorous tests. First, they measured the cells' ability to proliferate and self-renew, and found that some of them could divide into about 100 cells within a week. They also showed that the cells could indeed differentiate into endometrial tissue, and identified certain telltale proteins that are present in other types of stem cells.

Gargett, who is now also with Australia's Hudson Institute of Medical Research, and her colleagues went on to characterizeseveral types of self-renewing cells in the endometrium. But only the whiskered cells, called endometrial stromalmesenchymal stem cells, were truly "multipotent," with the ability to be coaxed into becoming fat cells, bone cells, or even the smooth muscle cells found in organs such as the heart.

Around the same time, two independent research teams made another surprising discovery: Some endometrial stromal mesenchymal stem cellscould be found in menstrual blood. Gargett was surprised that the body would so readily shed its precious stem cells. Since they are so important for the survival and function of organs, she didn't think the body would "waste" them by shedding them. But she immediately recognized the finding's significance: Rather than relying on an invasive surgical biopsy to obtain the elusive stem cells she'd identified in the endometrium, she could collect them via menstrual cup.

More detailed studies of the endometrium have since helped to explain how a subset of these precious endometrial stem cells dubbed menstrual stem cells end up in menstrual blood. The endometrium has a deeper basal layer that remains intact, and an upper functional layer that sloughs off during menstruation. During a single menstrual cycle, the endometrium thickens as it prepares to nourish a fertilized egg, then shrinks as the upper layer sloughs away.

Gargett's team has shown that these special stem cells are present in both the lower and upper layers of the endometrium. The cells are typically wrapped around blood vessels in a crescent shape, where they are thought to help stimulate vessel formation and play a vital role in repairing and regenerating the upper layer of tissue that gets shed each month during menstruation. This layer is crucial to pregnancy, providing support and nourishment for a developing embryo. The layer, and the endometrial stem cells that prod its growth, also appears to play an important role in infertility: An embryo can't implant if the layer doesn't thicken enough.

Endometrial stem cells have also been linked toendometriosis, a painful condition that affects roughly 190 million women and girls worldwide. Although much about the condition isn't fully understood, researchers hypothesize that one contributor is the backflow of menstrual blood into a woman's fallopian tubes, the ducts that carry the egg from the ovaries into the uterus. This backward flow takes the blood into the pelvic cavity, a funnel-shaped space between the bones of the pelvis. Endometrial stem cells that get deposited in these areas may cause endometrial-like tissue to grow outside of the uterus, leading to lesions that can cause excruciating pain, scarring and, in many cases, infertility.

Researchers are still developing a reliable, noninvasive test to diagnose endometriosis, and patients wait an average of nearly seven years before receiving a diagnosis. But studies have shown that stem cells collected from the menstrual blood of women with endometriosis have differentshapesandpatterns of gene expressionthan cells from healthy women. Several labs are working on ways to use these differences in menstrual stem cells to identify women at higher risk of the condition, which could lead to faster diagnosis and treatment. Menstrual stem cells may also have therapeutic applications. Some researchers working on mice, for example, have found that injecting menstrual stem cells into the rodents' blood can repair the damaged endometrium and improve fertility.

Other research in lab animals suggests that menstrual stem cells could have therapeutic potential beyond gynecological diseases. In a couple of studies, for example, injecting menstrual stem cells into diabetic micestimulated regeneration of insulin-producing cellsandimproved blood sugar levels. In another, treating injuries with stem cells or their secretions helpedheal wounds in mice.

A handful of small but promising clinical trials have found that menstrual stem cells can be transplanted into humans without adverse side effects. Gargett's team is also attempting to develop human therapies. She and her colleagues are using endometrial stem cells those taken directly from endometrial tissue, rather than menstrual blood to engineer a mesh to treat pelvic organ prolapse, a common, painful condition in which the bladder, rectum or uterus slips into the vagina due to weak or injured muscles.

The condition is often caused by childbirth. Existing treatments use synthetic meshes to reinforce and support weak pelvic tissues. But adverse immune reactions to these materials have led these meshes to be withdrawn from the market. Gargett's research so far conducted only in animal models suggests that using a patient's own endometrial stem cells to coat biodegradable meshes couldyield better results.

Despite the relative convenience of collecting adult multipotent stem cells from menstrual blood, research exploring and utilizing the stem cells' power and their potential role in disease still represents a tiny fraction of stem cell research, saysDaniela Tonelli Manica, an anthropologist at Brazil's State University of Campinas. As of 2020, she found, menstrual stem cell researchaccounted for only 0.25 percentof all mesenchymal cell research, while bone marrow stem cells represented 47.7 percent.

Manica attributes the slow adoption of menstrual stem cells in part to misogynistic ideas that uteruses are outside the norm, and to reactions of disgust. "There's certainly something of an 'ick factor' associated with menstrual blood," agreesVictoria Male, a reproductive immunologist at Imperial College London who coauthored an article aboututerine immune cellsin the 2023Annual Review of Immunology.

Cultural taboos surrounding menstruation and a general lack of investment in women's health research can make it difficult to get funding, says Gargett. Immunologist Male has faced similar challenges it was easier to obtain funding when she used to study immune cells in liver transplantation than it is now that she works on immune cells in the uterus, she says.

"If we want more research on menstrual fluid, we need more funding," says Male, noting that the logistics of collecting menstrual fluid over multiple days can be expensive. For that to happen, "we have to tackle sex and gender bias in research funding." Through more equitable investments, she and others hope, menstruation will be recognized as an exciting new frontier in regenerative medicine not just a monthly inconvenience.

Sneha Khedkar

This article was originally published by the Knowable Magazine on 29 January 2024.

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The untapped potential of stem cells in menstrual blood - Gavi, the Vaccine Alliance

Stopping the Pain and Saving Lives: Successful Treatments for Sickle Cell Disease – Charlotte Lozier Institute

The U.S. Food and Drug Administration (FDA) recently approved not just one, but two new gene therapies for sickle cell disease. The first, Casgevy, was co-developed by Vertex Pharmaceuticals and CRISPR therapeutics. The second, Lyfgenia, was developed by bluebird bio. What was all this gene editing and DNA swapping about, are the therapies successful, and is this an ethical advance in medicine?

Sickle cell disease is an inherited (genetic) condition that affects about 100,000 U.S. patients, and more than 20 million people globally. People with sickle cell have severe pain, anemia, and clogged blood vessels that can damage multiple organs. Half of adults with sickle cell disease die by their early 40s.

The disease name comes from the shape taken by red blood cells; instead of the normal flexible disc shape, cells form a sickle shape that can clump and block blood vessels to the point that organs and tissues do not receive oxygen. This can result in severe pain crises, blindness, stroke, and other organ damage.

Why do the red cells form a sickle shape, and how can gene editing reverse the disease? Sickling is the result of one small mutation in the DNA, a single letter of genetic code that is changed. Yet this single molecular change leads to profound changes in the character of the patients hemoglobin (the protein in red blood cells responsible for delivering oxygen to tissues throughout the body). One molecule of our normal adult hemoglobin contains four proteinstwo alpha-globin proteins and two beta-globin proteinscomplexed with an iron-containing heme molecule. Each red blood cell is basically a bag of hemoglobin, floating through the blood, grabbing oxygen and carrying it around the body to our cells and tissues.

The single genetic mutation in sickle cell leads to a single amino acid change in the beta-globin protein, changing the character of the protein so that it tends not to form oxygen-carrying molecules but rather causes the proteins to clump within the cell and form stiff rods, stretching the disc-shaped cells into a sickle shape.

It is important to note that during our development in the womb, our bodies use a slightly different form of hemoglobin, termed fetal hemoglobin, to carry oxygen. Fetal hemoglobin is made up of two alpha-globin proteins and two gamma-globin (rather than beta-globin) proteins complexed with heme. Around the time of birth, our body stops making gamma-globin by turning off that gene, and turning on the gene to start production of beta-globin for oxygen-carrying capacity once we are out of the womb.

Treatments for serious sickle cell disease have been few and difficult to obtain. While a couple of drugs and periodic red blood cell transfusions can ameliorate some of the diseases symptoms, so far only matched bone marrow adult stem cell transplants have been a curative option (more on this below.)

Genetic therapies such as the two now approved by the FDA aim to cure a disease, rather than simply manage its symptoms, attacking it at the genetic level to cause a permanent change. These two gene therapies are both what are termed somatic gene therapies. Their goal is to treat existing individuals and cure the disease without altering the germlinei.e., they are not heritable. In general, this type of gene therapy poses few ethical difficulties, although access to the treatment, including its cost, as well as complete informed consent regarding potential outcomes and side effects, can be issues.

On the other hand, genetic therapies which aim to prevent disease by altering the germline (heritable DNA) of eggs, sperm, or embryos, thereby affecting not only the treated (or manufactured) individual but also future generations, raise significant ethical concerns. The Charlotte Lozier Institutes Handbook of Nascent Human Beings has more information on the science, bioethics, and moral permissibility of genetic engineering and other new technologies.

The two newly approved gene therapies both accomplish their alleviation of sickle cell disease by altering bone marrow adult stem cells of the patient; theyve taken this route because using the patients own adult stem cells poses no problem of immune rejection of the therapy.Bone marrow adult stem cells are extracted from the patient and purified. In particular, the scientists are after what are called the CD34+ cells, which are the master stem cell for all blood and immune cells.The genetic alteration is done ex vivo, meaning in the lab and outside the patients body.

Casgevy, the therapy produced by Vertex, injects the CRISPR gene editing tool into the cells, targeting a small control region on the DNA that, when turned on, stops production of fetal hemoglobin, in particular the gamma-globin.Essentially, the enzyme makes a snip in the control region, turning off the inhibitor, thereby turning on production of gamma-globin.The result is that adult hemoglobin is replaced in the patient by fetal hemoglobin, which carries oxygen just fine.

Lyfgenia, produced by bluebird, uses a benign, inactivated virus as a vector to inject a modified form of normal beta-globin into the patients adult stem cells in the lab. The new DNA instructions then insert into the cells genome, where it produces normal adult hemoglobin and restores normal oxygen-carrying capacity.The slight modification in the inserted beta-globin DNA is a one amino-acid change that inhibits any aggregation of beta-globin, further eliminating the molecular problem for the patient.

For both genetic therapies, after the gene editing in the lab and quality control checks to make sure the adult stem cells are correctly altered, the cells are reinfused back into the patient. Prior to reinfusion, the patient gets a dose of chemotherapy to wipe out old faulty bone marrow adult stem cells and make space for the corrected cells.The altered adult stem cells go to the bone marrow and make themselves at home, start producing blood cells, and these new red blood cells carry oxygen normally, thus curing the patients of sickle cell disease.

Using adult stem cells, rather than fetal stem cells, as the vehicle for the genetic alteration showcases another role for this gold standard of stem cells, the only stem cell with a documented record of providing successful treatments. Direct transplant of normal beta-globin-containing adult stem cells has also been used successfully to treat sickle cell disease and related blood disorders. Until the approval of these new genetic therapies utilizing stem cells from the ailing patients themselves, adult stem cell transplant was considered the only curative treatment available for sickle cell disease and similar conditions. Since the transplant relies on finding matched donors for each patient, the cure has been limited. New research suggests, however, the possibility of using haploidentical (half-matched) transplants to increase accessibility to this critical adult stem cell treatment.

Freedom from sickle cell disease is available now using adult stem cell transplants. You can watch Desirees story to see the success of using adult stem cells from cord blood. You can watch more of Desiree as she discusses the transplant experience with two other patients. The success of adult stem cell therapies continues to demonstrate that the progress of science and medicine need not rely on ethically compromised research and treatment approaches.

David A. Prentice, Ph.D. is former Vice President and Director of Research for the Charlotte Lozier Institute. This article may also be accessed at the Christian Medical & Dental Associations website.

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Comparison of the Efficacy Between Regional Nerve Block and Ring Block as Local Anesthetic Techniques for Platelet … – Cureus

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Comparison of Efficacy of Platelet-Rich Plasma With and Without Topical Minoxidil for Hair Growth in Patients With … – Cureus

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Please choose I'm not a medical professional. Allergy and Immunology Anatomy Anesthesiology Cardiac/Thoracic/Vascular Surgery Cardiology Critical Care Dentistry Dermatology Diabetes and Endocrinology Emergency Medicine Epidemiology and Public Health Family Medicine Forensic Medicine Gastroenterology General Practice Genetics Geriatrics Health Policy Hematology HIV/AIDS Hospital-based Medicine I'm not a medical professional. Infectious Disease Integrative/Complementary Medicine Internal Medicine Internal Medicine-Pediatrics Medical Education and Simulation Medical Physics Medical Student Nephrology Neurological Surgery Neurology Nuclear Medicine Nutrition Obstetrics and Gynecology Occupational Health Oncology Ophthalmology Optometry Oral Medicine Orthopaedics Osteopathic Medicine Otolaryngology Pain Management Palliative Care Pathology Pediatrics Pediatric Surgery Physical Medicine and Rehabilitation Plastic Surgery Podiatry Preventive Medicine Psychiatry Psychology Pulmonology Radiation Oncology Radiology Rheumatology Substance Use and Addiction Surgery Therapeutics Trauma Urology Miscellaneous

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A low-cost device to make cell therapy safer – Tech Explorist

In cell therapy, clinicians reprogram some skin or blood cells from patients to create induced pluripotent stem cells. They coax these stem cells to transform into progenitor cells for treating spinal cord injury. These progenitors are then transplanted back into the patient to regenerate part of the injured spinal cord. However, pluripotent stem cells that dont entirely change into progenitors can form tumors.

Scientists at MIT and the Singapore-MIT Alliance for Research and Technology have developed a tiny device to improve cell therapy treatments with more excellent safety and effectiveness. They developed a microfluidic cell sorter to remove undifferentiated cells without damaging fully-formed progenitor cells.

This newly developed device can sort more than 3 million cells per minute without special chemicals. In the study, scientists found that combining many devices can sort more than 500 million cells per minute.

Pluripotent stem cells were generally larger than the progenitor cells derived from them. It happens because pluripotent stem cells have many genes that havent been switched off in their nucleus. As these cells specialize in specific functions, they suppress many genes that are no longer required, hence shrinking the nucleus. The microfluidic device leverages this size difference to sort the cells.

The plastic chip contains tiny channels that create an inlet for cells to enter, a spiral pathway, and four outlets where cells of different sizes are collected. When cells pass through the spiral at high speeds, various forces, including centrifugal forces, push them around. These forces help gather the cells at a specific point in the fluid stream based on their size, effectively separating them into different outlets.

The researchers discovered they could enhance the sorters performance by running it twice. First, they operate it at a lower speed, causing more giant cells to stick to the walls while smaller cells are sorted out. Then, they run it faster to separate the larger cells.

The device works similarly to a centrifuge, but it doesnt need human intervention to collect the sorted cells.

The device could remove almost 50% of larger cells in one pass. Whats more, the device doesnt use any filtration. The limitations with filters are that they become clogged or break down over time so that a filter-free device can be used for much longer.

Having demonstrated success on a small scale, the researchers are now moving on to larger studies and animal models to determine if the purified cells work better when introduced into living organisms.

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A low-cost device to make cell therapy safer - Tech Explorist

Scientists develop world’s first 3D-printed brain tissue that functions like human brain – WION

In a path-breaking scientific endeavour, researchers have created the worlds first 3D-printed brain tissue that behaves like a natural brain tissue. This is being considered a major leap towards the development of advanced solutions to neurological and neurodevelopmental disorders.

This will greatly aid research programmes for scientists specially focused on treatments for a broad range of neurological and neurodevelopmental disorders, such as Alzheimers and Parkinsons disease.

This could be a hugely powerful model to help us understand how brain cells and parts of the brain communicate in humans, Su-Chun Zhang, professor of neuroscience and neurology at UWMadisons Waisman Center, was quoted as saying by Neuroscience.

It could change the way we look at stem cell biology, neuroscience, and the pathogenesis of many neurological and psychiatric disorders, he added.

The 3D printer employed by scientists here ditched the traditional approach in favour of stacking layers horizontally. They situated brain cells, neurons grown from induced pluripotent stem cells, in a softer bio-ink gel than previous attempts had employed.

Watch:Are brain implants the future of computing?

The tissue still has enough structure to hold together but it is soft enough to allow the neurons to grow into each other and start talking to each other, Zhang added.

Yuanwei Yan, a scientist in Zhangs lab, said the tissues stayed relatively thin, which allowed the neurons to easily access oxygen and enough nutrients from the growth media.

The neurons communicate with each other, send signals and interact through neurotransmitters, and even form proper networks with support cells that were added to the printed tissue.

We printed the cerebral cortex and the striatum and what we found was quite striking, Zhang said. Even when we printed different cells belonging to different parts of the brain, they were still able to talk to each other in a very special and specific way, he added.

As per experts, the printing technique offers an advanced level of precision not seen in other approaches, including brain organoids, miniature organs used to study brains. The technique offers control over the types as well as arrangements of cells, with proper organisation and control.

This provides scientists with flexibility in their research endeavours, which paves the way for radical advancements in the field.

(With inputs from agencies)

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Scientists develop world's first 3D-printed brain tissue that functions like human brain - WION

Neurona Raises $120M, Buoyed by Early-Stage Data for Epilepsy Cell Therapy – BioSpace

Pictured: 3D illustration of stem cells used for cell therapy/iStock,Maksim Tkachenko

Neurona Therapeutics on Thursday announced that it has secured $120 million in funding, which will help it advance its pipeline of investigational off-the-shelf cell therapies.

The California-based biotech will use the money to advance its lead candidate NRTX-1001, a regenerative neural cell therapy candidate being assessed in a Phase I/II trial for drug-resistant mesial temporal lobe epilepsy (MTLE), the most common form of focal epilepsy that can trigger ongoing seizures despite medical treatment.

Neuronas financing on Thursday was co-led by Viking Global Investors and Cormorant Asset Management. Other institutional supporterssuch as UC Investments, UCB Ventures, Euclidean Capital, The Column Group and Alexandria Venture Investmentsalso participated in the funding round.

Neurona has pioneered development of a fully-differentiated cell therapy for drug-resistant focal epilepsy that is designed to be disease-modifying, repairing the affected neural network, and is yielding very promising initial clinical data, Raymond Kelleher, managing director at Cormorant, said in a statement, adding that NRTX-1001 could be a game-changer with its potential to control seizures and preserve neurocognitive function.

According to the biotechs website, NRTX-1001 is a cell therapy comprised of human inhibitory GABAergic interneurons, which can potentially address the underlying hyperactive neural networks in epileptic seizures.

In December 2023, at the annual meeting of the American Epilepsy Society, Neurona presented data from two patients enrolled in the Phase I/II study of NRTX-1001, who saw at least a 95% drop in overall seizure frequency more than one year after treatment. NRTX-1001 was also safe overall, with adverse events categorized as mild to moderate in severity.

Neurona is also testing NRTX-1001 in Alzheimers disease, for which it is currently in the preclinical evaluation stage.

Beyond NRTX-1001, Neurona will also channel some of Thursdays haul into its other pipeline projects including investigational myelinating glial cells and gene-edited cells, both for yet-undisclosed indications.

Neuronas funding comes nearly a year after the biotech laid off 18 employees, or 25% of its total headcount, to streamline its budget in the face of the current tight funding environment and extend available cash to support the ongoing clinical trial of NRTX-1001, a spokesperson told Fierce Biotech at the time.

The financing could also be a sign of an uptick in the industrys fundraising activities. This week alone, there have been two initial public offeringsKyverna and Metagenomiwhich follow the earlier debuts of Alto Neuroscience, Fractyl Health, ArriVent Biopharma and CG Oncology.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Read more from the original source:
Neurona Raises $120M, Buoyed by Early-Stage Data for Epilepsy Cell Therapy - BioSpace