from bone marrow, to repair and regenerate tissue following an ischemic event. The time window for giving the stem cells is about two weeks after the stroke. With intra-arterial delivery, the cells are delivered directly to the brain via the carotid artery, avoiding their becoming trapped in the lungs and liver, which occurs when stem cells have been administered intravenously. In the next couple of days after the procedure, the artery opened up by itself.
There is a limitation to treatments that open up arteries—they have to be done extremely urgently and even after they are done extremely urgently, only about 40 percent of the patients really recover significant brain function. Therefore, there is need for new therapies like stem cells to help the injured brain to recover. This trial will lead to the next study, in which approval can be sought for this kind of therapy; such approval would allow all doctors, not only in the United States but around the world, to use this therapy.
University of California
In an early test, researchers report they have safely injected stem cells into the brains of 18 patients who had suffered strokes and two of the patients showed significant improvement. All the patients saw some improvement in weakness or paralysis within six months of their procedures. The stem cells used in the study came from bone marrow donated by two people who were unrelated to the study participants. Special cells called mesenchymal stem cells were isolated from the marrow and grown in a lab, where they were treated with a gene that is thought to enhance healing abilities. The results have encouraged researchers to plan larger and longer tests of the procedure, which uses stem cells cultured from donated bone marrow.
University of Pittsburgh and Stanford University
About a decade ago, Douglas Kondziolka (now moved to New York University from Pittsburgh), led a promising trial of a different old lineage stem cell in older stroke patients. Because the current stem cells are more a modified and sophisticated type, researchers had to start over again with animal and safety tests. Researchers at University of Pittsburgh Medical Center (UPMC) and Stanford University are objectively working on recovery data after infusion of millions of stem cells directly into patients’ brains. The cells were extracted from adult bone marrow and given a booster containing a gene known as Notch, which is involved in the development of infant brains. The procedure ensues by making a burr hole through the skull and inserting a metal tube into the brain near the area of the stroke damage. The stem cells are then infused into the brain through the tube. Outcome is yet to be announced. No major side effects have been reported to date. Furthermore, the Stanford University–led team plans to use cells generated from human embryonic stem cells to improve recovery in the weeks and months following a stroke.
University of Texas Health Science Center at Houston
The University of Texas Health Science Center at Houston (UTHealth) has been named one of 25 regional stroke centers by the National Institutes of Health (NIH) and it is the only one in Texas. It is one of the first centers in the country to test stem cell therapies. From cooling the brain to infusing stem cells, UTHealth is working hard to change that. An international leader in research and clinical care, UTHealth was one of the original sites in the groundbreaking trial that found tissue plasminogen activator (tPA) could help stroke patients. Researchers are now studying autologous stem cells, drugs that can be used in combination with tPA, other potential clot busters, and brain cooling for stroke.
Sean Savitz, director of the stroke program at UTHealth, is pioneering the only randomized, double-blind, placebo-controlled, intra-arterial clinical trial in the world for ischemic stroke. The goal of the project is to study the safety and efficacy of a regenerative therapy called ALD-401, consisting of highly active and sophisticated isolated stem cells generated and developed by Aldagen Inc., a wholly owned subsidiary of Cytomedix Inc., that uses a patient’s own bone marrow stem cells and that can be administered between 13 and 19 days post stroke. The cells are administered into the carotid artery. Patients are followed for 12 months to monitor safety and to assess mental and physical function. Multiple centers have now signed on for the clinical trial.
Northwestern Memorial Hospital
Northwestern Medicine researchers are investigating a novel stem cell therapy known as SB623 that may hold the key to improving motor function following a disabling stroke. Northwestern is currently one of only a few sites in the nation enrolling participants in a landmark study to test the safety and efficacy of adult stem cell therapy for patients with stable ischemic stroke. While the study’s primary purpose is to examine the safety of SB623 stem cells, researchers will also seek to determine whether the cells are effective in improving stroke symptoms.
SB623 is derived from genetically engineered adult bone marrow cells from a healthy adult donor. Early participants have received 2.5 million cells, but as the study progresses, the dose will escalate to 5 million and eventually 10 million cells. Since SB623 cells are allogeneic, a single donor’s cells can be used to treat many other individuals. Participants in the study will be followed for up to two years, with periodic evaluations for safety and effectiveness in the improvement in motor function.
Even at this early phase, researchers recognize the potential of stem cell therapy. Stem cell therapy may hold the key to treating a wide range of neurological disorders that currently do not have many available therapies. The participants in the trial are the University of Pittsburgh Medical Center and Stanford University School of Medicine.
Thomas Jefferson University
Stem cells, with their ability to both stimulate endogenous repair mechanisms and replace dying neurons offer great promise as a potential stroke therapy. In a study conducted at Thomas Jefferson University, rat bone marrow stromal stem cells (BMSCs) were tracked after IV administration to rats with experimental stroke caused by middle cerebral artery occlusion (MCAO). In addition, the effects of BMSC treatment on blood cell composition, brain glia, and sensorimotor behavior were studied and compared to that which occurred spontaneously during the normal recovery process after stroke. It was found that the vast majority of radio labeled or fluorescently labeled BMSCs traveled to and remained in peripheral organs (lungs, spleen, liver) three days after IV injection in the MCAO rat. Once in the circulation, BMSCs also produced rapid alterations in host blood cell composition, increasing both neutrophil and total white blood cell count by six hours post injection.
In contrast, few injected BMSCs traveled to the brain and almost none endured there long term. Nonetheless, BMSC treatment produced dramatic changes in the number and activation of brain astroglia and microglia, particularly in the region of the infarct. These cellular changes were correlated with a marked improvement in performance on tests of sensory and motor function. It was concluded that the notable recovery in function observed after systemic administration of BMSCs to MCAO rats was likely due to the cellular changes in blood and/or brain cell number, activation state, and their cytokine/growth factor products.
University of Minnesota
Investigators in the Stem Cell Institute, University of Minnesota, in collaboration with the Departments of Neuroscience and Neurosurgery, are characterizing how neural stem cells, multipotent adult stem cells, or embryonic stem cells become mature neurons (nerve cells) and glial cells (non-nerve tissue of the brain and spinal cord). Studies employ innovative in vitro (in the lab) culture systems and state-of-the-art in vivo models (in the body or an organism) to determine the full potential of neural cells generated from stem cells.
University Hospitals Case Medical Center
A new national study looking at the safety and effectiveness of new medication developed from adult stem cells for the treatment of ischemic stroke opened at University Hospitals (UH) Case Medical Center. The Phase 2 study will use a cell therapy product called MultiStem. MultiStem is a proprietary medication made from a patented class of early adult stem cells called multipotent adult progenitor cells (MAPCs) that are obtained from the bone marrow. Hundreds of thousands to millions of doses can be made from the bone marrow cells of one donor.