oligodendrocytes

Researchers at Case Western Reserve University School of Medicine have developed a cutting-edge laboratory technique able to turn human stem cells – special cells able to grow into any type of cell in the body – into brain-like tissues in a culture dish. They intend to use their tool to study how myelination – the deposition of myelin around nerve cells – occurs in the central nervous system, and how diseases such as multiple sclerosis (MS) impair this process. The experimental protocol to grow these structures outside an organis) is described in the study, "Induction of myelinating oligodendrocytes in human cortical spheroids," published in the journal Nature Methods. These structures, called “oligocortical spheroids,” are small spheres that contain all the major cell types usually found in the human brain, including oligodendrocytes — cells that produce myelin, which is the fatty substance that insulates nerve fibers. Previous cerebral organoid techniques failed to include oligodendrocytes. “We have taken the organoid system and added the third major cell type in the central nervous system — oligodendrocytes — and now have a more accurate representation of cellular interactions that occur during human brain development,” Paul Tesar, PhD, associate professor of genetics and genome sciences at Case Western's medical school and the study's senior author, said in a press release. Oligodendrocytes are essential to good brain health. Without these cells, myelin production is hampered and nerve cells cannot communicate effectively, and eventually they start to deteriorate. This is the starting point for many neurological disorders caused by myelin defects, including MS and rare pediatric genetic disorders like Gaucher disease. Using this new organoid system and these myelin-producing cells, researchers intend to study the process of myelination — how it occurs in normal circumstances and how neurodegenerative diseases disrupt this process. “This is a powerful platform to understand human development and neurological disease,” Tesar said. “Using stem cell technology we can generate nearly unlimited quantities of human brain-like tissue in the lab. Our method creates a ‘mini-cortex,’ containing neurons, astrocytes, and now oligodendrocytes producing myelin. This is a major step toward unlocking stages of human brain development that previously were inaccessible.” Researchers not only demonstrated that they were capable of generating mature oligodendrocytes derived from human stem cells in vitro, but they also showed these cells were able to exert their function and produce myelin starting at week 20 in a culture dish. Their improved organoid system could also be used to test the effectiveness of potential myelin-enhancing treatments. “These organoids provide a way to predict the safety and efficacy of new myelin therapeutics on human brain-like tissue in the laboratory prior to clinical testing in humans,” said Mayur Madhavan, PhD, co-first author on the study. To prove this point, researchers treated organoids with promyelinating compounds known to enhance myelin production in mice, and measured the rate and extent of oligodendrocyte generation and myelination. Under normal conditions, adding promyelinating drugs to cultured organoids increased the rate and extent of oligodendrocyte generation and myelin production, the team reported. But results differed in important ways using diseased organoids.  Specifically, treating organoids generated from patients with Pelizaeus-Merzbacher disease — a fatal genetic myelin disorder — brought an in vitro recapitulation of the patients' symptoms. “Pelizaeus-Merzbacher disease has been a complicated disorder to study due to the many different mutations that can cause it and the inaccessibility of patient brain tissue,” said Zachary Nevin, PhD, co-first author on the study. “But these new organoids allow us to directly study brain-like tissue from many patients simultaneously and test potential therapies.” Altogether, these findings demonstrate that oligocortical spheroids could be a versatile in vitro system to study how myelination occurs in the central nervous system, and a possible model for testing new therapies for neurodegenerative disorders. “Our method enables generation of human brain tissue in the laboratory from any patient,” Tesar said. “More broadly, it can accurately recapitulate how the human nervous system is built and identify what goes wrong in certain neurological conditions.”

A better understanding of the processes behind a continual and healthy renewal of myelin — the fatty, protective substance wrapping nerve cell fibers — may now exist. Researchers identified an enzyme, called PRMT5, that they believe regulates the number of myelin-producing cells in the brain and spinal cord. Their discovery…

Blocking a protein receptor called muscarinic type 3 (M3R) could be an effective way to promote remyelination in multiple sclerosis (MS) patients, according to a State University of New York at Buffalo (UB) study in mice. The research, “Muscarinic receptor M3R signaling prevents efficient remyelination by…

Researchers have unveiled a new cell death mechanism called pyroptosis — also known as “fiery death” — as a main factor driving neurodegeneration and loss of myelin in people with multiple sclerosis (MS). An inhibitor of pyroptosis, currently undergoing testing in human clinical trials for epilepsy, decreased central nervous system inflammation…

A chemical compound called indazole chloride promotes repair of myelin, the protective layer of nerve fibers, through “beneficial” inflammation in a mouse model of multiple sclerosis (MS), a study reports. The preclinical research, “Increase in chemokine CXCL1 by ERβ ligand treatment is a key mediator in…

A molecule responsible for preventing the repair of white matter in the brain, a process critical to treating multiple sclerosis (MS) and cerebral palsy, has been identified. The research, “A TLR/AKT/FoxO3 immune-tolerance like pathway disrupts the repair capacity of oligodendrocyte progenitors,” was published in The Journal…

A new project aimed at boosting the development of new therapies for multiple sclerosis (MS) and other demyelinating diseases recently won $1.7 million in funding from the National Institutes of Health (NIH). In the five-year study, a research team at the University at Buffalo (part of the State University…

Genetically modified human umbilical cord blood cells can help nerve cells recover the myelin layer necessary for normal functioning, researchers found in a preclinical study. This finding may support the development of cell-based therapeutic approaches to help patients with spinal cord injuries or demyelinating diseases, such as multiple sclerosis (MS).

Inhibiting an oxidative stress enzyme reduced nerve cell damage and promoted the formation of new nerve cells, a multiple sclerosis study in mice showed. It also helped regenerate cells that produce the nerve cell-protecting myelin sheath, researchers said. The team used a mouse model of the progressive form of MS in…

University at Buffalo researchers are working on ways to improve multiple sclerosis patients’ cognitive function and to repair damage to the mylein coating that protects nerve cells. The National Multiple Sclerosis Society awarded the researchers more than $1.1 million to conduct the studies. One, “The Effects of Working Memory…

Clene Nanomedicine says its pre-clinical studies demonstrate the remyelination effects of CNM-Au8, supporting its potential to treat multiple sclerosis (MS) and other demyelinating disorders. Clene presented its data in a session, “Nanocrystalline Gold As a Novel Remyelination Therapeutic for Multiple Sclerosis,” that took place at the third annual Americas…

The nerve-cell-protecting myelin sheath’s failure to remove cholesterol after the membrane has been damaged limits its ability to regenerate, German researchers report. Their finding has important implications for multiple sclerosis because a hallmark of the disease is nerve cell deterioration stemming from damaged myelin. Cholesterol is a waxy, fatty substance…

A natural metabolite called taurine may boost the effectiveness of existing multiple sclerosis (MS) therapies, researchers say. Taurine helps oligodendrocytes, which are cells responsible for myelin production, to fully mature and activate the remyelination process of damaged nerve cells. The findings were reported in the study, “…

A research team at the University of Illinois College of Medicine has received $300,000 from the Falk Medical Research Trust to develop a novel drug delivery method that could improve the treatment of patients with multiple sclerosis. Established in 1979, the Dr. Ralph and Marian Falk Medical Research Trust - Catalyst Award is granted every year to a dozen U.S. research groups. It provides one year of funding to high-risk, high-reward projects to complete preliminary studies. Catalyst Program winners who achieve their goals can then enroll in the Falk Transformational Awards Program, which offers $1 million for two years to further support the projects. The UIC team, led by Ernesto Bongarzone and Maria Givogri, hope to transform naturally occurring small vesicles released by several cell types into drug targeted delivery vehicles. Cells commonly use these vesicles to communicate with each other. They pack inside the vesicles with many cell products, like proteins and small RNA molecules, then release them into the bloodstream and cerebrospinal fluid. These vesicles can travel to distant places in the body until they find and fuse with their target cell, dumping their cargo. However, the content of vesicles may not always be good, as they have been shown to play a role in spreading cancer, said fellow anatomy and cell biology professor Givogri. "There is much more to learn about how they function in this way,” she added. The team will use the Catalyst Award to test different methods of vesicles production from mesenchymal stem cells. They will also engineer these vesicles to specifically target oligodendrocytes in the brain and spinal cord. Oligodendrocytes are cells that specialize in producing the nerve cell’s protective myelin layer. The efficacy and safety of this new delivery method will be tested in mice. After completing these preliminary studies, the team expects to apply for further funding. The UIC researchers plan to use the vesicles to transport and deliver small RNA molecules, called microRNAs, that can boost myelin production.

A blood-clotting protein called fibrinogen prevents myelin production and blocks the neuron remyelination repair process in mice, a study finds. The study, “Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage,” appeared in the journal Neuron. Its conclusions offer new insights and…

Researchers, using two different kinds of stem cells in rats, were able to regenerate oligodendrocytes — myelin-producing brain cells that are defective in multiple sclerosis (MS). They were also able to grow adult neural stem cells in laboratory cultures and prod them to develop into oligodendrocytes. The exact cause of MS is unknown — including what triggers attacks on myelin — but the loss of oligodendrocytes seen in the disease is known to play a role in its progression. Nerve cells in the brain send their signals through their axons, long arm-like structures that extend out from the centers of the nerve cells. The signals are electrical pulses transmitted along the length of an axon. Oligodendrocytes provide the insulation — called myelin — that wraps around axons, speeding up the transmission of electrical signals through the nerve cells. Loss or malfunction of oligodendrocytes means that signaling in the brain is impaired. It is this slowing of signaling that is thought to cause MS symptoms. Researchers from the Heinrich-Heine-University, Germany, with support from British and Chilean colleagues, designed a novel approach to regenerate oligodendrocytes, according to a press release. Stem cells are immature cells that give rise to differentiated cells — cells with a specific function, such as oligodendrocytes. Adult neural stem cells can divide and produce nerve cells and other brain cells, including oligodendrocytes. However, in normal circumstances, the regeneration of cells that take place in the human brain is not enough to repair the damage seen in MS. The researchers set out to find conditions that would promote the differentiation of adult human NSCs into oligodendrocytes. They discovered that another type of stem cell, mesenchymal stem cells (MSCs), could provide the signals required. First they tested their system in rats, and found that by using factors produced by human MSCs, they could induce the growth of new oligodendrocytes in the animals. Then they grew adult NSCs in the laboratory, and using the same factors from human MSCs were able to promote the establishment of oligodendrocytes in the cultured cells.

A new study on rats indicates that the antidepressant Luvox promotes the production of the neuron-protecting coating that is deficient in multiple sclerosis. It also significantly decreased the severity of the animals' disease, researchers said, adding that Luvox promoted the production of the protective coating by helping stem cells evolve into oligodendrocytes, or cells that generate what is known as the myelin sheath. Patients with MS often experience anxiety and depression, with recent studies suggesting their rate of depression is three times higher than those with other long-term medical conditions. In addition to drugs targeting the underlying mechanisms of MS, such as inflammation and myelin loss, doctors often recommend that patients take antidepressants. The most common treatments they prescribe for moderate or severe depression are a class of serotonin re-uptake inhibitors that include Luvox. Few studies have looked at antidepressants' effects on animal models of MS, however. That prompted researchers to investigate Luvox's impact on both laboratory and rat models of the disease. Researchers used embryonic neural stem cells in their study. Luvox prompted laboratory stem cells to evolve into other types of cells, including neurons, oligodendrocytes, and astrocytes, which have several roles, including supporting and repairing neurons. Prozac also promoted stem cell differentiation — but at levels 10 times higher than those of Luvox. A key finding was that that Luvox significantly decreased the severity of the disease in the rats. Another important finding was that Luvox significantly reduced demyelination and immune cell infiltration in the rats' spinal cords. It also decreased the rats' expression of pro-inflammatory proteins known as cytokines. Overall, this study “demonstrated that fluvoxamine, in addition to its confirmed role in mood disorder therapy, could serve as a candidate clinical treatment for attenuating [reducing] neuro-inflammation and stimulating oligodendrogenesis in neurological diseases, particularly MS patients.”

B-cells of patients with relapsing-remitting multiple sclerosis (RRMS) secrete substances that are toxic to both neurons and neuron-protecting myelin-forming cells, causing both kinds to die, according to a study. Despite analyses of numerous inflammatory and other factors believed to drive MS processes, researchers were unable to identify the molecules that are toxic, however. Dr. Robert Lisak of Wayne State University in Detroit, Dr. Amit Bar-Or of McGill University in Montreal and their teams are now working on identifying the factor, and learning if the process is also involved in progressive MS. Their study, “B-cells from patients with multiple sclerosis induce cell death via apoptosis in neurons in vitro,” was published in the Journal of Neuroimmunology. It demonstrated that B-cells gathered from the blood of RRMS patients killed lab-grown neurons and oligodendrocyte cells, which form myelin, a protecting coating for nerve cells. Deterioration of the myelin coating and the death of neurons are hallmarks of MS. An earlier study the team conducted indicated that B-cells from MS patients could kill oligodendrocytes. But since the experiments involved only three patients and three controls, the team scaled up their experiments to include 13 patients and an equal number of controls. Both rat and human neurons died when mixed with MS-derived B-cells. In contrast, B-cells from healthy people had little or no impact on the survival of the brain cells. Researchers also discovered that the secreted toxic molecules had no impact on other types of central nervous system cells — astrocytes and microglia. The toxins killed only neurons and myelin-producing cells. The B-cells triggered a process called apoptosis, or programmed cell death, researchers said. This is basically a suicide program. It tells a cell to die when exposed to stressful factors or toxins. The process differs from cell disintegration. Despite thoroughly screening about 40 inflammation-related substances, researchers were unable to identify any factors that caused the cells to die. The National MS Society and the Research Foundation of the MS Society of Canada funded the research, which the U.S. society highlighted in a news release. In the newest phase of the study, researchers will try to learn more about the processes underlying neuron and myelin-related cell deaths and identify the factors responsible. In addition to testing B-cells from progressive MS patients, the team will examine patients with other autoimmune conditions to see if the process is unique to MS or not. Researchers increasingly realize that B-cells are important to MS processes. This observation was underscored by U.S. regulators' approval of the B-cell depleting therapy Ocrevus (ocrelizumab) at treatment for both relapsing and primary progressive MS.

A physical scaffold that allows lab-grown brain cells to grow in a three-dimensional manner is giving scientists a whole new way of studying the regeneration of myelin, nerve coatings whose damage is at the heart of multiple sclerosis. The scaffold is allowing researchers to test large numbers of compounds for…

Brain stem cells from primary progressive multiple sclerosis (PPMS) patients lack the ability to repair brain damage and to trigger the maturation of protective myelin-producing cells, a surprising study with far-reaching implications indicates. The study also showed that stem cells from individual patients reacted differently to compounds developed to trigger…

British scientists have accelerated from weeks to days the process by which stem cells generate brain cells, which could open the door to new treatment approaches for diseases such as multiple sclerosis. Researchers at the Wellcome Trust Sanger Institute and colleagues at the University of Cambridge developed the…

Using a small RNA molecule belonging to the family of microRNAs (miRs), scientists could restore myelin in nerve cells and improve limb function in mouse models of human multiple sclerosis (MS). The study, “miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS,” was published in…

The United States has granted a patent to Kadimastem’s stem cell-based technology for treating multiple sclerosis (MS) and other diseases of the nervous system. The patent involves the technology the company used to produce supporting cells in the central nervous system derived from human stem cells, including myelin-producing cells. The United…

The absence of epigenetic factors in myelin-producing oligodendrocyte cells make sure that myelin production is switched off in the adult brain. Targeting these factors may be a way of triggering myelin regeneration in multiple sclerosis (MS), and a step toward personalized medicine for this disease, Dr. Patrizia Casaccia said in a talk…

Australia has granted a patent to RegeneRx Biopharmaceuticals for an active ingredient in a therapy that could benefit multiple sclerosis (MS) patients. The patent is for Thymosin beta 4 (Tβ4), the driving force in the company’s RGN-352 treatment. RGN-352 promotes myelination, or the production of protective myelin sheaths for damaged neurons and other nerve…

Scientists at the University of Buffalo have identified a critical step in the process of nerve myelination after birth, a discovery that holds promise for the development of more effective therapies for neurodegenerative diseases like multiple sclerosis (MS). The research involved the study of voltage-operated calcium channels, which initiate many physiological…

A study found that the cells responsible for the production of myelin selectively introduce a myelin-insulating layer in a particular set of neuronal axons in the brain’s white matter. This represents a step forward in the basic mechanisms that may underlie neurological disorders, including multiple sclerosis (MS). Also, a newly developed method…

Tamoxifen (brand name, Nolvadex), a widely used treatment for breast cancer, can also be used to treat myelin loss in patients with multiple sclerosis (MS), a new study suggests. The finding, by a team of researchers at the University of Cambridge, U.K., was published in a study titled “…

RegeneRx Biopharmaceuticals announced that it has received an Intent to Grant notice from the European Patent Office (EPO) regarding a patent for its proprietary molecule Thymosin beta 4 (Tβ4), a potential therapy for multiple sclerosis (MS) designed to promote remyelination. The patent will cover the use of Tβ4 in a composition for treating or reducing…

A cell therapy product derived from human umbilical cord blood cells may be a promising treatment approach for patients with demyelinating diseases, such as multiple sclerosis (MS) or leukodystrophy, according to a recent study developed at the Duke University Medical Center. The study, “A cord blood monocyte–derived cell…