stanford stroke stem cell study

Jan 24 2018. Steinberg, who has more than 15 years’ worth of experience in work with stem cell therapies for neurological indications, is the paper’s lead and senior author. Sonia Olea Coontz had a stroke in 2011 that affected the movement of her right arm and leg. Andres RH, Horie N, Slikker W, Keren-Gill H, Zhan K, Sun GH, Sheikh LA, McMillan EL, Schaar BT, Svendsen CN, Bliss TM. Our current paradigm is that hNSCs transplanted into the host stroke brain, rather than exerting their effects directly by replacing damaged tissue, secrete factors and interact with the stroke milieu in a manner that stimulates endogenous repair mechanisms that are activated by stroke. A stem cell treatment helps stroke patients regain motor function. 2 As the population continues to age, the incidence of acute stroke and the prevalence of stroke-related disability are expected to increase. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu. Figure 3. Researchers at Stanford reported that they are “stunned” by the results of an experimental treatment to treat stroke patients. Stem Cell Types for Chronic Stroke Stem cells are self-renewing and capable of differentiation into multiple cell types. Once we understand the mechanisms by which transplanted hNSCs exert therapeutic effects, we can exploit their full clinical potential as well as predict and prevent potential side effects. Using axonal and dendritic tracing methods we found that hNSCs enhance neuronal structural plasticity by increasing dendritic branching and axonal transport. In, 2000 the Center added a Neurocritical Care Program. “Yet we see that patients’ recovery is sustained for greater than one year and, in some cases now, more than two years.”. Bruce Goldman is a science writer in the Office of Communications. The great majority of survivors end up with enduring disabilities. Stem cell therapy for stroke study A new study conducted by Michael Levy and colleagues has found the intravenous injection of allogeneic mesenchymal stem cells to be both a safe and effective treatment option for post-stroke long term recovery. During the procedure, patients’ heads were held in fixed positions while a hole was drilled through their skulls to allow for the injection of SB623 cells, accomplished with a syringe, into a number of spots at the periphery of the stroke-damaged area, which varied from patient to patient. Illustration by Francesco Bongiorni Six months after a stroke, doctors don’t expect improvement in a patient’s recovery, says Stanford professor and chair of neurosurgery Gary Steinberg , MD, PhD. “This could revolutionize our concept of what happens after not only stroke, but traumatic brain injury and even neurodegenerative disorders. Understanding how hNSCs interact with the stroke-injured brain to induce recovery is crucial to maximizing their effectiveness. Importantly, the stroke patients’ postoperative improvement was independent of their age or their condition’s severity at the onset of the trial. Support teaching, research, and patient care. SanBio also funded and helped in designing the trial, but did not participate in its execution. Learn how we are healing patients through science & compassion, Stanford team stimulates neurons to induce particular perceptions in mice's minds, Students from far and near begin medical studies at Stanford. Consequently, we are studying optimal parameters for successful transplantation strategies in rodent models of stroke; these parameters will depend on the cross talk between the graft and the host and will facilitate understanding of the mechanisms underlying cell-enhanced functional recovery. A second purpose is to determine whether SB623 might improve stroke symptoms. Steinberg said it’s likely that factors secreted by the mesenchymal cells during their early postoperative presence near the stroke site stimulates lasting regeneration or reactivation of nearby nervous tissue. A Study of Modified Stem Cells in Stable Ischemic Stroke. These effects are mediated in part by vascular endothelial growth factor (VEGF). Red: pre-synaptic marker synapsin; Green: post-synaptic marker PSD95. We showed at a rudimentary level that hNSCs reduce the number of microglia/macrophage present in the brain after stroke (1). We have found (eg., Horie et al Stem Cells 2011) that transplanted hNSCs can attenuate some of the direct effects of stroke damage, such as inflammation and vascular leakage1. 8 In addition, a Phase 2 trial for subacute … “In a simple sense, the stem cell transplant turns the adult brain in a neonatal of infant brain which recovers well after a stroke or other injury,” added Prof Steinberg. Right: Human neural progenitor cells (red) are found in close proximity to blood vessels (green). No relevant blood abnormalities were observed. They also call for new thinking regarding the permanence of brain damage, said Gary Steinberg, MD, PhD, professor and chair of neurosurgery. (The rest were performed at the University of Pittsburgh.) (C) 3D reconstruction of colocalized puncta. For most patients, at least a full year had passed since their stroke — well past the time when further recovery might be hoped for. The specific loss of function incurred depends on exactly where within the brain the stroke occurs, and on its magnitude. Controlled study of stereotactic, intracranial injection of SB623 cells in patients with fixed motor deficits from ischemic stroke Official Title A Double-Blind, Controlled Phase 2b Study of the Safety and Efficacy of Modified Stem Cells (SB623) in Patients With Chronic Motor Deficit From Ischemic Stroke Interestingly, the implanted stem cells themselves do not appear to survive very long in the brain. But if we can figure out how to jump-start these damaged brain circuits, we can change the whole effect. “It was designed primarily to test the procedure’s safety. Some studies compare healthy people to those who have a specific disease. Steinberg is the principal investigator of that trial. Into these patients’ brains the neurosurgeons injected so-called SB623 cells —mesenchymal stem cells derived from the bone marrow of two donors and then modified to beneficially alter the cells’ ability to restore neurologic function. “Human embryonic stem cell-based therapies have the potential to help treat this complex disease,” Steinberg said, adding that he hopes the cells from this study can be used in human stroke trials within five years. Figure 2. Preclinical studies have shown that these cells begin to disappear about one month after the procedure and are gone by two months. “It felt like it was almost dead. For this trial, unlike the great majority of transplantation procedures, the stem cell recipients received no immunosuppressant drugs. We are now interested in how the hNSCs alter inflammation, what sub-populations of immune cells are affected, and how this relates to hNSC-induced recovery after stroke. It was focused on the use of stem cells and recovery from a stroke and featured three great guests: Dr. Gary Steinberg, chief of Neurosurgery at Stanford, Sonia Coontz, a patient of Dr. Steinberg’s, and CIRM’s own Science Officer Dr. Lila Collins. The primary purpose of the clinical study is to determine the safety of a modified stem cell SB623 when administered to chronic, stable ischemic stroke patients. Now 36, Coontz had a stroke in May 2011. In fact, they may actively suppress the immune system. Stanford-led clinical trial shows broader benefits of acute-stroke therapy. Differences in synaptic resolution by (A) confocal microscopy, and (B, C) array tomography. Zolpidem, better known by the trade name Ambien, increased the rate at which mice that had strokes recovered their pre-stroke sensory acuity and motor coordination. Support Lucile Packard Children's Hospital Stanford and child and maternal health. Preclinical data from our lab and others have demonstrated that stem cell transplantation can enhance stroke recovery. Support teaching, research, and patient care. Stanford Medicine is closely monitoring the outbreak of novel coronavirus (COVID-19). Stanford researchers have found that injecting stem cells directly into the brains of recovering stroke sufferers is more than just safe – it actually reverses brain damage, something previously thought impossible by science. The use of stem cells … In addition to clinical trials that accept healthy participants, there are other clinical studies at Stanford Medicine that also seek healthy participants. The use of stem cells is allowing patients with little hope for recovery to suddenly talk and walk again, according to the study published in the Journal of Stroke and Cerebrovascular Diseases. Afterward, patients were monitored via blood tests, clinical evaluations and brain imaging. At six months out from a stroke, you don’t expect to see any further recovery.”. The primary purpose of the clinical study is to determine the safety of a modified stem cell SB623 when administered to chronic, stable ischemic stroke patients. In the study, published in the journal Neuropsychopharmacology, the researchers took blood samples from a family with a high incidence of schizophrenia. Theoretically, the results of the stem cell research experiment could lead to better treatments for brain damage resulting from strokes, spinal cord injuries, traumatic brain injury, and even, potentially, Alzheimer’s disease. 1 In the United States alone, there are an estimated 795 000 strokes annually, making this the leading cause of long-term disability. We recently held our first ever Facebook Live event. “We thought those brain circuits were dead. If the results of the Stanford experiment can be replicated in a large-scale study, that is. Although approved therapies for ischemic stroke exist, to be effective they must be applied within a few hours of the event — a time frame that often is exceeded by the amount of time it takes for a stroke patient to arrive at a treatment center. Then, using the iPSC method, they turned those cells into brain neurons and compared them to the neurons of individuals with no family history of schizophrenia. In preclinical studies, though, they’ve not been found to cause problems by differentiating into unwanted tissues or forming tumors. Dr. Wesley McKeithan, Stanford Imagine having a tool you could use to quickly test lots of different drugs against a disease to see which one works best. Our center is a designated comprehensive stroke center and provides rapid “After my surgery, they woke up,” she said of her limbs. With permission from Dr. Stephen Smith. Although more than three-quarters of them suffered from transient headaches afterward — probably due to the surgical procedure and the physical constraints employed to ensure its precision — there were no side effects attributable to the stem cells themselves, and no life-threatening adverse effects linked to the procedure used to administer them, according to a paper, published online June 2 in Stroke, that details the trial’s results. Perhaps most notably, there was an overall 11.4-point improvement on the motor-function component of the Fugl-Meyer test, which specifically gauges patients’ movement deficits. Pre- and post-synaptic marker colocalization as seen with array tomography, an imaging method co-invented by Stephen Smith, PhD and Kristina Micheva, PhD at Stanford. Preclinical data from our lab and others have demonstrated that stem cell transplantation can enhance stroke recovery. The notion was that once the brain is injured, it doesn’t recover — you’re stuck with it. In vitro, functional assays identified several hNSC-secreted factors that can increase neurite sprouting (eg., Steinberg et al Brain 2011). Their ability to move around has recovered visibly. Steinberg began testing this in a small trial that ran between 2011 and 2013. For the trial, the investigators screened 379 patients and selected 18, whose average age was 61. Stroke Center The Stanford Stroke Center offers you the most advanced stroke treatments and leads the advancement of stroke care for patients nationwide. Easily harvested from bone marrow, they appear to trigger no strong immune reaction in recipients even when they come from an unrelated donor. She enrolled in the Stanford trial after finding out about it during an online search. With permission from Dr. Stephen Smith. * indicates lesion. A stroke leaves a permanent gap in the brain that can destroy a person’s ability to speak and move normally. The Stanford Stroke Center was founded in 1992 by vascular neurologist Gregory Albers, MD, interventional neuroradiologists Michael Marks, MD, and vascular neurosurgeon Gary Steinberg, MD, PhD. That’s unprecedented. Long Term Effects On Recipients of Hematopoietic Stem Cell Transplantation Stanford is currently accepting patients for this trial. Building on this observation that transplanted hNSCs can induce structural plasticity in the post-stroke brain we are now focusing on changes that can be induced at the synaptic level. Sonia Olea Coontz, of Long Beach, California, was one of those patients. Some patients experienced transient nausea and vomiting, and 78 percent had temporary headaches related to the transplant procedure. The patients, all of whom had suffered their first and only stroke between six months and three years before receiving the injections, remained conscious under light anesthesia throughout the procedure, which involved drilling a small hole through their skulls. “My right arm wasn’t working at all,” said Coontz. Scale bar = 100 μm (50 μm in inset, except 3 week inset: 25 μm). Strikingly, VEGF produced by transplanted hNSCs (human central nervous system stem cells grown as neurospheres or hCNS-SCns) also enhanced the endogenous repair mechanism of vascular regeneration (Figure 1), which supports our idea that transplanted stem cells enhance host repair mechanisms to promote functional recovery. “We know these cells don’t survive for more than a month or so in the brain,” he added. Email him at, Stanford Health Care (formerly Stanford Hospital & Clinics), Lucile Packard Children's Hospital Stanford, Stroke recovery in mice improved by Ambien, Targeted brain stimulation aids stroke recovery in mice, scientists find. Yet, patients showed significant recovery by a number of measures within a month’s time, and they continued improving for several months afterward, sustaining these improvements at six and 12 months after surgery. Scale bar = 10 µm. Horie N, Niizuma K, Pereira MP, Sun GH, Keren-Gill H, Encarnacion A, Shamloo M, Hamilton SA, Jiang K, Huhn S, Palmer T, Bliss TM. Learn how we are healing patients through science & compassion, Stanford team stimulates neurons to induce particular perceptions in mice's minds, Students from far and near begin medical studies at Stanford. “This was just a single trial, and a small one,” cautioned Steinberg, who led the 18-patient trial and conducted 12 of the procedures himself. Interim data from the PISCES Phase 1 trial for chronic stroke showed that intracerebral implantation of modified human neural stem cells was safe and seemed to be associated with improvements of neurological function in some of the stroke scales; these data were considered sufficient to warrant initiating a Phase 2 trial (PISCES II). Study of Modified Stem Cells (SB623) in Patients With Chronic Motor Deficit From Ischemic Stroke Controlled study of stereotactic, intracranial injection of SB623 cells in patients with fixed motor deficits from ischemic stroke STEM CELL THERAPY offers enormous promise for the majority of the 795,000 Americans yearly who suffer a stroke yet currently have no pharmacological therapy to promote recovery. The initial vascular damage of stroke triggers a cascade of damaging events that occur days after the initial infarct. Inflammation plays a pivotal role in the extent of brain damage and recovery after a stroke. Stroke damage encompasses a wide range of pathologies. Individual synapses are well resolved. People disabled by a stroke demonstrated substantial recovery long after the event when modified adult stem cells were injected into their brains. Together they continue to direct the Stanford Stroke program today. In each case, the stroke had taken place beneath the brain’s outermost layer, or cortex, and had severely affected motor function. Inset shows higher magnification of hCNS-SCns. After modified stem cells were injected into her brain as part of a clinical trial, she says her limbs "woke up." Some lost functionality often returns, but it’s typically limited. Stanford’s Department of Neurosurgery also supported the work. Support Lucile Packard Children's Hospital Stanford and child and maternal health. In a multicenter study led by Stanford researchers, the number of stroke patients who died or required confinement to nursing homes was nearly cut in half, the biggest improvement seen in any stroke-related trial to date. In a recent medical study, Stanford researchers say a new stem cell experiment is transforming the lives of stroke patients. A second purpose is to determine whether SB623 might improve stroke symptoms. The unique advantage of using stem cells for post-stroke recovery lies in the multiple modalities through which they enhance recovery. “This wasn’t just, ‘They couldn’t move their thumb, and now they can.’ Patients who were in wheelchairs are walking now,” said Steinberg, who is the Bernard and Ronni Lacroute-William Randolph Hearst Professor in Neurosurgery and Neurosciences. California Institute for Regenerative Medicine, Discovery Research, Gladstone Institutes, Heart Disease/Stroke, iPS Cells, Stem cell research calcific aortic valve disease , Christina V. Theodoris , CIRM , Deepak Srivastava , Dr. Anna Malashicheva , induced pluripotent stem cells , science This has led to major efforts to advance stem cell therapy for stroke to the clinic, including our human neural stem cell (hNSC) product, NR1 cells, which is transitioning to the clinic via a California Institute for Regenerative Medicine (CIRM)-funded Disease Team program. A dedicated page provides the latest information and developments related to the pandemic. Our approach integrates the advanced proteomic imaging technique, array tomography, to accurately identify and count excitatory and inhibitory synapses (Figures 2 & 3), and electrophysiology techniques to measure functional changes at the synaptic and circuit level. Stem cells injected into distant arteries or veins travel to the site of a stroke in the brain to fuel the repair process. Optogenetically stimulating mice’s brains five days after stroke improved the animals’ motor control and brain biochemistry. This has led to major efforts to advance stem cell therapy for stroke to the clinic, including our human neural stem cell (hNSC) product, NR1 cells, which is transitioning to the clinic via a California Institute for Regenerative Medicine (CIRM)-funded Disease Team program . About 85 percent of all strokes are ischemic: They occur when a clot forms in a blood vessel supplying blood to part of the brain, with subsequent intensive damage to the affected area. Stanford Medicine is leading the biomedical revolution in precision health, defining and developing the next generation of care that is proactive, predictive and precise. And the prevailing consensus among neurologists is that virtually all recovery that’s going to occur comes within the first six months after the stroke. Stanford researchers studying the effect of stem cells injected directly into the brains of stroke patients said Thursday that they were "stunned" by the extent to … Posts about Hemorrhagic stroke written by Kevin McCormack We recently held our first ever Facebook Live event. Injecting modified, human, adult stem cells directly into the brains of chronic stroke patients proved not only safe but effective in restoring motor function, according to the findings of a small clinical trial led by Stanford University School of Medicine investigators. It was focused on the use of stem cells and recovery from a stroke and featured three great guests: Dr. Gary Steinberg, chief of Neurosurgery at Stanford, Sonia Coontz, a patient of Dr. Steinberg’s, and CIRM’s own Science Officer Dr. Lila Collins. Horie N(1), Pereira MP, Niizuma K, Sun G, Keren-Gill H, Encarnacion A, Shamloo M, Hamilton SA, Jiang K, Huhn S, Palmer TD, Bliss TM, Steinberg GK. 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