is exogenous (meaning outside the body) transplantation, whereby stem cells are harvested, purified, and then partially or completely differentiated prior to being transplanted into patients. The exogenous repair strategy harnesses the power of stem cells from a different angle than the endogenous strategy. Rather than stimulating resident stem cells into action, stem cells are first harvested from patients or donors and then manipulated in the lab prior to being transplanted into a patient. The harvested stem cells can be purified and expanded in number and partially or completely differentiated into progeny of the type required to repair damaged tissue.
A stroke is the loss of brain function due to a disturbance in the blood supply to the brain by either a lack of blood flow caused from a blockage or by hemorrhaging. A stroke was the second most frequent cause of death worldwide in 2011–taking the lives of 6.2 million people. (Blausen Medical Communications)
Many medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering. One of regenerative medicine’s greatest goals is to develop new treatments for stroke. Many researches are being conducted around the globe on using stem cells as a therapy for stroke. The following is a review of major researches being conducted at various universities in the United States.
University of Miami Miller School of Medicine
In the past, it was thought that stem cells would regenerate into new neurons, the cells in the brain, but it is now becoming quite clear that especially stem cells that are from the bone marrow play more of a nursing function in that they stimulate the body’s own mechanisms of repair and enhance them and make them work harder to get the repair done much better than if the stem cells were not present. They act like small factories, secreting a number of substances that stimulate the brain surrounding the injured environment and help with recovery. The first two stroke patients had been enrolled in a phase 2 clinical trial of a revolutionary new treatment for ischemic stroke being conducted at the University of Miami/Jackson Memorial Hospital in 2013.
The trial, using a patient’s own bone marrow stem cells, was the first intra-arterial stroke stem cell trial in the United States. The trial examined the efficacy of ALD-401, derived 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.
