A Stem Cell Treatment for Stroke


A new clinical trial is enrolling people who are dealing with the disabling effects of stroke.

Every year approximately 800,000 Americans suffer a stroke. Strokes or TIAs for “trans-ischemic attacks” result from blockage of a blood vessel in the brain. The lack of blood flow to the brain results in the death of those cells that starve from oxygen, and the aftermath of a stroke is remarkably unpleasant; long-term disability, permanent brain damage, and even death. Stroke is the leading cause of adult disability and extracts an annual burden of $62 billion on the US economy. Physical therapy can improve the deficits caused by a stroke, but there are, to date, no good treatments to ameliorate the condition of a stroke patient.

In the hopes of creating new options for stroke patients, researchers at Northwestern Medicine are examining a new regenerative treatment for stroke that utilizes a novel stem cell line called SB623. This stem cell line might provide increased motor function to stroke victims.

Northwestern is only one of three sites in the nation enrolling patients in a clinical study to evaluate the efficacy and safety of adult stem cell therapy in stroke patients. Patient who have suffered from so-called “ischemic stroke” suffer from impaired bodily functions that includes such conditions as paralysis, weakness on one side, difficulty with speech and language, vision issues, and cognitive deficits.

Joshua Rosenow, the principal investigator of this clinical trial, is the director of Functional Neurosurgery at Northwestern Memorial Hospital. Rosenow had this to say of this clinical study: “Two million brain cells die each minute during a stroke making it critical to get treatment fast at the earliest sign of symptoms once brain damage occurs, there’s very little that can be done medically to reverse it. While this study is only a preliminary step towards understanding the healing potential of these cells, we are excited about what a successful trial could do for a patient population that hs very limited therapeutic options.”

The primary purpose of this study is to examine the safety of SB623 stem cells. However, there is an added motive behind this study, and that is to determine if SB623 cells are efficacious as a treatment for stroke patients. SB623 cells are genetically engineered mesenchymal stem cells from adult bone marrow.

Richard Bernstein, the director of Northwestern Memorial’s Stroke Center, weighed in: “Although not proven in humans, these stem cells (SB623) have been shown to promote healing and improve function when administered in animal models of stable stroke. The cells did not replace the neurons destroyed by stroke, but instead they appeared to encourage the brain to heal itself and promote the body’s natural regenerative process. Eventually, the implanted stem cells disappeared.”

Rosenow added, “In this study, the cells are transplanted into the brain using brain mapping technology and scans, allowing us to precisely deposit the cells in the brain adjacent to the area damaged by the stroke.”

The first participants have received injections of 25 million cells, but as the study progresses, the dose will escalate to 5 million and eventually 10 million cells. Since SB623 cells are allogeneic, which is to say that they come from someone other than the patient, a single donor’s cells can be used to treat as many other patients. All subjects in this study will be followed for up to two years with periodic evaluations for safety and effectiveness in improving motor function.

Bernstein explained, “Stroke can be a very disabling and life-changing event. Even just a slight improvement in function could make a huge difference for a person impacted [sic] by stroke. To potentially regain movement or speech is a very exciting prospect. In the animal models, the improvements appeared to remain even after the implanted stem cells disappeared.

Even at this early stage in this clinical trial, there is a great deal of excitement over the potential for stem cell therapy. Rosenow echoed this excitement when he said, “Of these cells are proven effective in improving, or even reversing brain damage, the implications of a successful outcome reach far beyond just stroke. Stem cell therapy may hold the key to treating a wide range of neurological disorders that do not have many available therapies. The Northwestern team is very excited to be a part of this groundbreaking trial.”

Participants for this trial must be between the ages of 18 and 75 years old, must have had an ischemic stroke in the last six to 36 months. They should have moderate to severe symptoms with impaired motor function. Full inclusion and exclusion criteria are available online. Full inclusion and exclusion criteria are available online. The FDA-approved phase 1-11 study is expected to enroll 18 subjects nationwide and this study is slated to last up to two years.

Other sites participating in the trial are the University of Pittsburgh Medical Center and Stanford University School of Medicine. The trial is funded by SanBio, Inc., a regenerative medicine company that developed the SB623 stem cell line.

SB623 papers:

1. Extracellular matrix produced by bone marrow stromal cells and by their derivative, SB623 cells, supports neural cell growth.  Aizman I, Tate CC, McGrogan M, Case CC.

  • J Neurosci Res. 2009, 87(14):3198-206.

2. Notch-induced rat and human bone marrow stromal cell grafts reduce ischemic cell loss and ameliorate behavioral deficits in chronic stroke animals. Yasuhara T, Matsukawa N, Hara K, Maki M, Ali MM, Yu SJ, Bae E, Yu G, Xu L, McGrogan M, Bankiewicz K, Case C, Borlongan CV.  Stem Cells Dev. 2009, 18(10):1501-14

3. Reversal of dopaminergic degeneration in a parkinsonian rat following micrografting of human bone marrow-derived neural progenitors. Glavaski-Joksimovic A, Virag T, Chang QA, West NC, Mangatu TA, McGrogan MP, Dugich-Djordjevic M, Bohn MC.  Cell Transplant. 2009, 18(7):801-14.

4.

Tate CC, Fonck C, McGrogan M, Case CC. Cell Transplant. 2010,19(8):973-84.

5. Glial cell line-derived neurotrophic factor-secreting genetically modified human bone marrow-derived mesenchymal stem cells promote recovery in a rat model of Parkinson’s disease.  Glavaski-Joksimovic A, Virag T, Mangatu TA, McGrogan M, Wang XS, Bohn MC. J Neurosci Res. 2010, 88(12):2669-81.

6. Comparing the immunosuppressive potency of naive marrow stromal cells and Notch-transfected marrow stromal cells.

  • Dao MA, Tate CC, Aizman I, McGrogan M, Case CC.

J Neuroinflammation. 2011, 8(1):133.

7.

Tate CC and Case CC.

  • Chapter in “Neurological Disorders”, InTech, 2012.

Stem Cells Allow Kidney Transplant Recipients to Live Without Anti-Rejection Drugs


Researchers from Northwestern Medicine And University of Louisville are in the midst of a clinical trial to examine the use of stem cell infusions to re-educate the immune system of recipients of transplanted organs. Such re-education of the immune system might completely eliminate the need for anti-rejection medicines.

Organ transplant recipient must take several pills each day for the remainder of their lives. These medicines are drugs that suppress the immune system, and these drugs have many undesirable side effects. Prolonged use of these drugs can cause high blood pressure, diabetes, infections, heart disease, and cancer. Therefore a stem cell-based approach that obviates the need for drugs that inhibit the immune system would offer transplant recipients better quality of life and few health risks for transplant patients.

Joseph Leventhal, a transplant surgeon at Northwestern Memorial Hospital said, “The preliminary results are exciting and may have a major impact on organ transplantation in the future. With refinement, this approach may prove to be applicable to the majority of patients receiving the full spectrum of solid organ transplants.” Leventhal is the main author of this study in collaboration with Suzanne Ildstad, who is the director of the Institute of Cellular Therapeutics at the University of Louisville. The study is, in fact, one of the first of its kind, since it does not require that the organ donor and recipient do not have to be tissue matched.

For standard kidney transplants, the organ donor, who has agreed to donate a kidney, provides their kidney for transplantation to the recipient. In this study, the organ donor not only provides a kidney, but also a small quantity of blood cells. Approximately one month before the transplant, the organ donor gives some bone marrow by means of a procedure called “apheresis.”

Apheresis removes whole blood from a patient, and then uses a centrifuge-like instrument to separate blood components. These separated portions are removed and the remaining components used for retransfusion. The blood components are separated into fluids, otherwise known as plasma, platelets, and white blood cells. From the white cell fraction, a group of cells that the study cells “facilitating cells” are isolated. The organ recipient’s bone marrow is partially ablated with radiation.

The kidney is then transplanted into the recipient’s body, and one day later, the facilitating cells are given to the recipient. Because the organ recipient’s bone marrow has been semi-ablated, the facilitating cells have space to grow without competition from the recipient’s bone marrow. The goal of this is to make within the recipient two bone marrow stem cell systems that are completely functional in one person. The patient is given anti-immune system drugs, but he or she is slowly weaned off them, with the goal of all anti-rejection drugs being ended within one year of the transplant. To qualify for this study, patients must have compatible blood types

Ildstad provided this insight, “This is something I have worked for my entire life.”  Ildstad pioneered the discovery of the “facilitating cell.”  This trial is ongoing, but the initial results are immensely encouraging, since some transplant patients seem to not need their anti-rejection medicines anymore even though they now have a kidney inside them that was not tissue matched.  Specifically, five of eight people who underwent this treatment protocol were able to stop all immunosuppressive therapy within a year after their kidney and stem-cell transplants,. Note that four of these five patients received kidneys that came from unrelated donors. Notably, all of these patients maintained entirely donor-derived immune systems with no signs of Graft-versus-Host disease.  Ildstad and her team have since treated seven more people. “We continue to see good results,” she says. This could easily revolutionize solid organ transplantation.