Sonia Olea Coontz had a stroke in 2011 that affected the movement of her right arm and leg. The initial vascular damage of stroke triggers a cascade of damaging events that occur days after the initial infarct. 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. 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 In addition to clinical trials that accept healthy participants, there are other clinical studies at Stanford Medicine that also seek healthy participants. 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. Stroke Center The Stanford Stroke Center offers you the most advanced stroke treatments and leads the advancement of stroke care for patients nationwide. 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. 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. Neuroplasticity is another endogenous repair mechanism that occurs during functional recovery. People disabled by a stroke demonstrated substantial recovery long after the event when modified adult stem cells were injected into their brains. Posts about Hemorrhagic stroke written by Kevin McCormack We recently held our first ever Facebook Live event. “My right arm wasn’t working at all,” said Coontz. Using axonal and dendritic tracing methods we found that hNSCs enhance neuronal structural plasticity by increasing dendritic branching and axonal transport. For this trial, unlike the great majority of transplantation procedures, the stem cell recipients received no immunosuppressant drugs. A stem cell treatment helps stroke patients regain motor function. Steinberg is the principal investigator of that trial. “Some patients couldn’t walk,” Steinberg said. Mesenchymal stem cells are the naturally occurring precursors of muscle, fat, bone and tendon tissues. 2 As the population continues to age, the incidence of acute stroke and the prevalence of stroke-related disability are expected to increase. 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). At six months out from a stroke, you don’t expect to see any further recovery.”. Researchers at Stanford reported that they are “stunned” by the results of an experimental treatment to treat stroke patients. Scale bar = 100 μm (50 μm in inset, except 3 week inset: 25 μm). * indicates lesion. 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. 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. Optogenetically stimulating mice’s brains five days after stroke improved the animals’ motor control and brain biochemistry. The great majority of survivors end up with enduring disabilities. 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. 1 In the United States alone, there are an estimated 795 000 strokes annually, making this the leading cause of long-term disability. Support Lucile Packard Children's Hospital Stanford and child and maternal health. Right: Human neural progenitor cells (red) are found in close proximity to blood vessels (green). 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. Steinberg began testing this in a small trial that ran between 2011 and 2013. “We know these cells don’t survive for more than a month or so in the brain,” he added. 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. Some 800,000 people suffer a stroke each year in the United States alone. “There are close to 7 million chronic stroke patients in the United States,” Steinberg said. Banner photos Left: Transplanted stem cells (green) migrating towards blood vessels in stroke-damaged brain. Figure 1 (A) hCNS-SCns (red: human cytoplasmic marker SC121) survive and migrate over time (green: lectin-positive blood vessels; blue: DAPI). 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. Support Lucile Packard Children's Hospital Stanford and child and maternal health. Mark Rightmire. With permission from Dr. Stephen Smith. “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. “Others couldn’t move their arm.”. 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. 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. 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 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. 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. Figure 2. Preclinical data from our lab and others have demonstrated that stem cell transplantation can enhance stroke recovery. Looking for healthy volunteers Healthy volunteers play a vital role in clinical studies, helping researchers learn how to keep people well. In fact, they may actively suppress the immune system. 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. After modified stem cells were injected into her brain as part of a clinical trial, she says her limbs "woke up." Differences in synaptic resolution by (A) confocal microscopy, and (B, C) array tomography. 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. Stem Cell Types for Chronic Stroke Stem cells are self-renewing and capable of differentiation into multiple cell types. A second purpose is to determine whether SB623 might improve stroke symptoms. Our center is a designated comprehensive stroke center and provides rapid Their ability to move around has recovered visibly. If the results of the Stanford experiment can be replicated in a large-scale study, that is. Sonia Olea Coontz, of Long Beach, California, was one of those patients. 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. “After my surgery, they woke up,” she said of her limbs. These effects are mediated in part by vascular endothelial growth factor (VEGF). 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. 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. Andres RH, Horie N, Slikker W, Keren-Gill H, Zhan K, Sun GH, Sheikh LA, McMillan EL, Schaar BT, Svendsen CN, Bliss TM. Consequently, only a small fraction of patients benefit from treatment during the stroke’s acute phase. Figure 3. That’s unprecedented. The SB623 cells were provided by SanBio Inc., a biotechnology company based in Mountain View, California. In vitro, functional assays identified several hNSC-secreted factors that can increase neurite sprouting (eg., Steinberg et al Brain 2011). 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 . “It felt like it was almost dead. “If this treatment really works for that huge population, it has great potential.”. “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. Importantly, the stroke patients’ postoperative improvement was independent of their age or their condition’s severity at the onset of the trial. 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. 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. 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. The notion was that once the brain is injured, it doesn’t recover — you’re stuck with it. 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. Stroke damage encompasses a wide range of pathologies. Jan 24 2018. Inflammation plays a pivotal role in the extent of brain damage and recovery after a stroke. 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. 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. The unique advantage of using stem cells for post-stroke recovery lies in the multiple modalities through which they enhance recovery. Afterward, patients were monitored via blood tests, clinical evaluations and brain imaging. “Yet we see that patients’ recovery is sustained for greater than one year and, in some cases now, more than two years.”. The use of stem cells … “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. Long Term Effects On Recipients of Hematopoietic Stem Cell Transplantation Stanford is currently accepting patients for this trial. Support teaching, research, and patient care. 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 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. (The rest were performed at the University of Pittsburgh.) 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