Stroke Patients Improve After Stem Cell Treatments


Neurologists at Imperial College, London have conducted a small pilot study in stroke patients who received stem cell treatments after their strokes. To date, their patients have shown tentative signs of neurological recovery six months after receiving the stem cell treatment.

According to the physicians attending these patients, all five patients who participated in the study have improved after the therapy. Even though these results are hopeful, larger and better controlled trials are required to confirm if the implanted stem cells are responsible for the improvements in these patients. Brain scans of the patients showed that damage caused by the stroke had reduced over time. However, similar improvements are seen in stroke patients as part of the normal recovery process.

When assessed after their six-month check ups, all of the participating patients fared better on standard measures of disability and impairment that are normally caused by stroke. Once again, it is difficult to determine if these improvements result from the stem cell treatments or from standard hospital care.

This pilot study was designed to assess only the safety of the experimental therapy (phase I clinical trial) and with so few patients and no control group to compare them with, it is impossible to draw conclusions about the effectiveness of the treatment at this time.

Paul Bentley is a consultant neurologist at Imperial College London, and his group is presently applying for funding to run a more powerful randomized, controlled trial on this stem cell therapy, which, Bentley hopes, could include at least 50 patients by next year.

“The improvements we saw in these patients are very encouraging, but it’s too early to draw definitive conclusions about the effectiveness of the therapy,” said Soma Banerjee, a lead author and consultant in stroke medicine at Imperial College Healthcare National Health System (NHS) Trust. “We need to do more tests to work out the best dose and timescale for treatment before starting larger trials.”

All five patients who participated in this study were treated within seven days of suffering a severe stroke. Each patient had a bone marrow sample extracted from their hip bones, and these bone marrow cells were processed in the laboratory to isolated the stem cells that give rise to blood cells and blood vessel lining cells (so-called CD34+ cells). These stem cells were infused into one of the main arteries that supplies blood to the brain.

CD34+ cells do not grow into fresh brain tissue, but they might release pro-healing chemicals that suppress inflammation and recruit and stimulate other cells to grow within the damaged brain tissue. Some of the implanted CD34+ cells might also form new blood vessels, said Bentley.

Four out of five of the patients had the most serious type of stroke, and typically, only 4% of these patients survive and are able to live independently after six months. In the pilot study, published in Stem Cells Translational Medicine, all four were alive and three were independent six months later.

“Although they mention some improvement of some of the patients, this could be just chance, or wishful thinking, or due to the special care these patients may have received simply because they were in a trial,” said Robin Lovell-Badge, head of developmental genetics at the MRC’s National Institute for Medical Research in London.

Caution is certainly required in the interpretation of this pilot study, but I think that these results definitely merit a Phase II trial to determine if the improvements are stem cell-independent or stem cell-dependent.

Patient’s Own Peripheral Blood Stem Cells Benefits Stroke Patients


A study conducted in Taiwan has examined the ability of a patient’s circulating peripheral blood stem cells to benefit stroke patients.

In this study, one of two groups of stroke patients received injections of their own peripheral blood stem cells (PBSCs) directly into the brain but the other group received standard care. Those patients who received the PBSCs experienced some improvement in stroke scales and functional capabilities. Patients who received their own PBSCs also were given injections of granulocyte-colony stimulating factor (G-CSF), which seems to protect the nervous system after trauma to it.

“In this phase 2 study, we provide the first evidence that intracerebral injection of autologous (self-donated) PBSCs can improve motor function in those who have suffered a ,” said stroke and have motor deficits as a result,” said Woei-Cheng Shyu of the China Medical University, who is the corresponding author of this study. “Our study demonstrates that this therapeutic strategy was feasible and safe in stroke patients who suffered a prior stroke, but within five years from the onset of symptoms.”

Strokes, also known as trans-ischemic attacks (TIAs) result from blockage in blood vessels that feed the brain. The lack of blood flow to the brain starves it of oxygen, and the cells of the brain begin to die off. Because neuronal death as a result of stroke limits functional recovery, stem cell therapy is advancing as a potentially effective regenerative treatment for stroke.

Also, in many types of stem cell trials, PBSCs are the stem cell of choice. The ease of isolating these cells without invasive procedures makes them the stem cell choice for many clinical trials. In order to utilize PBSCs, patients must amplify their supply of PBSCs, and injections of G-CSF seems to do just that.

In this study, all patients had suffered a prior stroke as long as five years prior to being treated.

At the end of the 12-month follow-up, the group of 15 patients with neurological deficits who received the PBSC injections into the brain experienced neurological and functional improvements, according to several different clinical measurements.

On the other hand, the 15-patient control group who had neurological deficits but did not receive the PBSC injections did not experience the same beneficial results.

In the experimental group, nine of the 15 patients showed proper activation of the motor nerves after stimulating that part of the brain with a magnet. This procedure, called transcranial magnetic stimulation or TMS, places a magnet above skull, directly above the part of the brain you want to stimulate. The rapidly changing magnetic field generated by the magnet produces weak electrical currents in the brain, which stimulates nearby neurons. In this experiment, researchers targeted the precentral gyrus, which is the portion of the brain where the primary motor cortex. Because strokes sometimes kill off neurons in the primary motor cortex, stimulation of the primary motor cortex will not lead to stimulation of motor nerves, but in this experiment, 9 of 15 patients who received the PBSC injections who positive motor evoke potential or MEPs after TMS. Why this ratio was not 15 out of 15 remains unclear at this time.

primary motor cortex

One of the main conclusions of this work, is that “Despite this success, it should be noted that this was a preliminary study and, due to the small number of patients, are tentative. In the future we plan to conduct a multi-center, large-scale, double-blind, placebo-controlled randomized studies [sic] to better evaluate the effect of PBSC implantation in patients suffering from the effects of past stroke.”

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.