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. Long Term Effects On Recipients of Hematopoietic Stem Cell Transplantation Stanford is currently accepting patients for this trial. This 3-D reconstruction of a small volume (6 x 6 x 2 µm) shows the pre-synaptic marker synapsin (magenta) and the post-synaptic marker of glutamatergic synapses PSD95 (green). 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. And we’ve learned that they’re not.”. Understanding how hNSCs interact with the stroke-injured brain to induce recovery is crucial to maximizing their effectiveness. “After my surgery, they woke up,” she said of her limbs. The notion was that once the brain is injured, it doesn’t recover — you’re stuck with it. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu. 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. Figure 1 (A) hCNS-SCns (red: human cytoplasmic marker SC121) survive and migrate over time (green: lectin-positive blood vessels; blue: DAPI). We recently held our first ever Facebook Live event. Scale bar = 100 μm (50 μm in inset, except 3 week inset: 25 μm). “This could revolutionize our concept of what happens after not only stroke, but traumatic brain injury and even neurodegenerative disorders. Consequently, only a small fraction of patients benefit from treatment during the stroke’s acute phase. “It felt like it was almost dead. A Study of Modified Stem Cells in Stable Ischemic Stroke. If the results of the Stanford experiment can be replicated in a large-scale study, that is. Stroke Center The Stanford Stroke Center offers you the most advanced stroke treatments and leads the advancement of stroke care for patients nationwide. After modified stem cells were injected into her brain as part of a clinical trial, she says her limbs "woke up." A second purpose is to determine whether SB623 might improve stroke symptoms. Figure 2. Steinberg is the principal investigator of that trial. 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 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. 2 As the population continues to age, the incidence of acute stroke and the prevalence of stroke-related disability are expected to increase. Looking for healthy volunteers Healthy volunteers play a vital role in clinical studies, helping researchers learn how to keep people well. 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. A second purpose is to determine whether SB623 might improve stroke symptoms. The next day they all went home. 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. “We know these cells don’t survive for more than a month or so in the brain,” he added. Some lost functionality often returns, but it’s typically limited. Stroke damage encompasses a wide range of pathologies. In each case, the stroke had taken place beneath the brain’s outermost layer, or cortex, and had severely affected motor function. 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. No relevant blood abnormalities were observed. A stroke leaves a permanent gap in the brain that can destroy a person’s ability to speak and move normally. 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. 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. The study, called PISCES III, will research if an investigational drug product (DP), which is made from stem cells, will help improve function in stroke survivors with limited movement in arms and/or legs six to 12 months following an (C) 3D reconstruction of colocalized puncta. 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). In addition to clinical trials that accept healthy participants, there are other clinical studies at Stanford Medicine that also seek healthy participants. Bruce Goldman is a science writer in the Office of Communications. Sonia Olea Coontz had a stroke in 2011 that affected the movement of her right arm and leg. “Others couldn’t move their arm.”. 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. 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. Stanford Medicine integrates research, medical education and health care at its three institutions - Stanford University School of Medicine, Stanford Health Care (formerly Stanford Hospital & Clinics), and Lucile Packard Children's Hospital Stanford. SanBio also funded and helped in designing the trial, but did not participate in its execution. In the study, published in the journal Neuropsychopharmacology, the researchers took blood samples from a family with a high incidence of schizophrenia. Posts about Hemorrhagic stroke written by Kevin McCormack We recently held our first ever Facebook Live event. That’s unprecedented. Eighteen volunteers at Stanford and the University of Pittsburgh Medical Center agreed to have the cells—derived from donor bone marrow and cultured by the Bay Area company SanBio—injected into their brains. Stanford Medicine is leading the biomedical revolution in precision health, defining and developing the next generation of care that is proactive, predictive and precise. 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. Transplanted stem cell-secreted vascular endothelial growth factor effects poststroke recovery, inflammation, and vascular repair. * indicates lesion. Importantly, the stroke patients’ postoperative improvement was independent of their age or their condition’s severity at the onset of the trial. The specific loss of function incurred depends on exactly where within the brain the stroke occurs, and on its magnitude. A stem cell treatment helps stroke patients regain motor function. 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. Stanford’s Department of Neurosurgery also supported the work. Differences in synaptic resolution by (A) confocal microscopy, and (B, C) array tomography. For this trial, unlike the great majority of transplantation procedures, the stem cell recipients received no immunosuppressant drugs. Banner photos Left: Transplanted stem cells (green) migrating towards blood vessels in stroke-damaged brain. 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. 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. 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. 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. Individual synapses are well resolved. 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. With permission from Dr. Stephen Smith. 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 . Substantial improvements were seen in patients’ scores on several widely accepted metrics of stroke recovery. For more information, please e-mail stemcellstudy@stanford.edu. Some 800,000 people suffer a stroke each year in the United States alone. (The rest were performed at the University of Pittsburgh.) Stem Cell Therapy While stem cells are still being used in clinical trials, there is evidence that, combined with clot busting and mechanical thrombectomy, therapy enhances recovery. “If this treatment really works for that huge population, it has great potential.”. Now 36, Coontz had a stroke in May 2011. 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. Afterward, patients were monitored via blood tests, clinical evaluations and brain imaging. Stem Cell Types for Chronic Stroke Stem cells are self-renewing and capable of differentiation into multiple cell types. 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. 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. 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. 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 In a recent medical study, Stanford researchers say a new stem cell experiment is transforming the lives of stroke patients. Stanford-led clinical trial shows broader benefits of acute-stroke therapy. A new randomized, double-blinded multicenter phase-2b trial aiming to enroll 156 chronic stroke patients is now actively recruiting patients. She enrolled in the Stanford trial after finding out about it during an online search. The use of stem cells … Inset shows higher magnification of hCNS-SCns. Steinberg began testing this in a small trial that ran between 2011 and 2013. But if we can figure out how to jump-start these damaged brain circuits, we can change the whole effect. 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. Mesenchymal stem cells are the naturally occurring precursors of muscle, fat, bone and tendon tissues. 8 In addition, a Phase 2 trial for subacute … Using axonal and dendritic tracing methods we found that hNSCs enhance neuronal structural plasticity by increasing dendritic branching and axonal transport. The promising results set the stage for an expanded trial of the procedure now getting underway. The initial vascular damage of stroke triggers a cascade of damaging events that occur days after the initial infarct. “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. “My right arm wasn’t working at all,” said Coontz. 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. 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. “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. Andres RH, Horie N, Slikker W, Keren-Gill H, Zhan K, Sun GH, Sheikh LA, McMillan EL, Schaar BT, Svendsen CN, Bliss TM. Some studies compare healthy people to those who have a specific disease. Stroke occurs in 15 million individuals each year worldwide, and is the second leading cause of mortality. These effects are mediated in part by vascular endothelial growth factor (VEGF). 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. Preclinical studies have shown that these cells begin to disappear about one month after the procedure and are gone by two months. 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. 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. Preclinical data from our lab and others have demonstrated that stem cell transplantation can enhance stroke recovery. Red: pre-synaptic marker synapsin; Green: post-synaptic marker PSD95. A dedicated page provides the latest information and developments related to the pandemic. 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. At six months out from a stroke, you don’t expect to see any further recovery.”. “I used a wheelchair a lot.”. “There are close to 7 million chronic stroke patients in the United States,” Steinberg said. Together they continue to direct the Stanford Stroke program today. Preclinical data from our lab and others have demonstrated that stem cell transplantation can enhance stroke 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. Mark Rightmire. Right: Human neural progenitor cells (red) are found in close proximity to blood vessels (green). 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. 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. For the trial, the investigators screened 379 patients and selected 18, whose average age was 61. That’s been a goal of stem cell researchers for many years but For most patients, at least a full year had passed since their stroke — well past the time when further recovery might be hoped for. My right leg worked, but not well.” She walked with a noticeable limp. They also call for new thinking regarding the permanence of brain damage, said Gary Steinberg, MD, PhD, professor and chair of neurosurgery. 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. With permission from Dr. Stephen Smith. 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. People disabled by a stroke demonstrated substantial recovery long after the event when modified adult stem cells were injected into their brains. (B): hCNS-SCns-treated animals compared with buffer-treated animals show significantly improved behavioral recovery after stroke 1. 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. Researchers at Stanford reported that they are “stunned” by the results of an experimental treatment to treat stroke patients. California Institute for Regenerative Medicine (CIRM)-funded Disease Team program, Transplanted stem cell-secreted VEGF effects post-stroke recovery, inflammation, and vascular repair, Human neural stem cells enhance structural plasticity and axonal transport in the ischemic brain, Lucile Packard Children's Hospital Stanford. Inflammation plays a pivotal role in the extent of brain damage and recovery after a stroke. Easily harvested from bone marrow, they appear to trigger no strong immune reaction in recipients even when they come from an unrelated donor. “Yet we see that patients’ recovery is sustained for greater than one year and, in some cases now, more than two years.”. 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. In fact, they may actively suppress the immune system. The ongoing work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill. Other Stanford co-authors of the study are Neil Schwartz, MD, PhD, clinical associate professor of neurology and neurological sciences and of neurosurgery; and former neurosurgery fellow Jeremiah Johnson, MD, now at the University of Texas Health Science Center in San Antonio. 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. Support teaching, research, and patient care. In vitro, functional assays identified several hNSC-secreted factors that can increase neurite sprouting (eg., Steinberg et al Brain 2011). 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. The great majority of survivors end up with enduring disabilities. Figure 3. The SB623 cells were provided by SanBio Inc., a biotechnology company based in Mountain View, California. Support Lucile Packard Children's Hospital Stanford and child and maternal health. Support teaching, research, and patient care. Interestingly, the implanted stem cells themselves do not appear to survive very long in the brain. Our center is a designated comprehensive stroke center and provides rapid 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 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. “Older people tend not to respond to treatment as well, but here we see 70-year-olds recovering substantially,” Steinberg said. 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. In preclinical studies, though, they’ve not been found to cause problems by differentiating into unwanted tissues or forming tumors. 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 … “Some patients couldn’t walk,” Steinberg said. In a recent medical study, Stanford researchers say a new stem cell experiment is transforming the lives of stroke patients. “We thought those brain circuits were dead. Optogenetically stimulating mice’s brains five days after stroke improved the animals’ motor control and brain biochemistry. 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. Of patients benefit from treatment during the stroke ’ s acute phase and tissues. Pivotal role in the extent of brain damage and recovery after stroke improved animals. 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