- Stroke is a leading cause of death and chronic disability in
- Recovery in stroke patients hampered
by serious infections and tissue damage due to an exaggerated immune
- Early stem cell therapy aids better
recovery in stroke patients by modulating the immune response
- Stem cell therapy is safe and well-tolerated
in stroke patients
stem cell therapy within 36 hours to stroke
patients improves long-term recovery according
to research conducted by the Department of Neurology at the Medical College of
Georgia at Augusta University. The findings of their study have been published
in the journal Lancet Neurology
Why Give Stem Cells in Stroke Patients
in stroke patients can be affected by increased risk of infections and tissue
damage, due to unnecessary destructive inflammation. Stem cell
therapy, especially if given early, can modulate the immune response
promote better recovery in the long-term.
‘Stem cell therapy could be an useful adjunct to existing therapies such as tissue-plasminogen activator (tPA) therapy or endovascular procedure in stroke patients.’
Details of the Study
- The study was conducted between
October 2011 and December 2015 in 33 centers across the United Kingdom and
the US. Patients included 129
adults with moderately severe stroke.
- A dose of 400 million cells was administered
initially to a handful of patients to establish safety. Following this,
the dose was increased to 1,200 million cells for most of the patients.
- While half the patients received the
stem cells, the remaining received placebo.
- Both groups of patients had received
conventional treatments including tissue plasminogen activator (tPA)
to dissolve the clot, or an endovascular operation to remove it.
timing of the therapy ranged between 24-48 hours, though earlier animal studies indicate
that 24-36 hours was the optimal time for the treatment. This was due to
some centers needing more time to thaw and prepare the stem cells.
Results of the Study
patients were initially followed up at three months but 80 percent of the
volunteers were followed up at one year.
indicated that in the long-term, patients who
had received stem cell therapy continued to recover with decreased incidence of
infections and lesser disability
compared to the placebo group.
is solid evidence from our basic science work and now some indicators from this
phase 2 patient trial
these stem cells can safely help dial back the body's immune response to stroke
injury that can ultimately further damage the brain and body," said Dr.
David C. Hess, stroke specialist and chairman of the Department of Neurology at
the Medical College of Georgia at Augusta University.
conducted by former
MCG neuroscientist Dr. Cesario V. Borlongan, pediatric neurologist and
professor emeritus Dr. James Carroll and Hess, showed that the stem cells
would be most beneficial if administered within two days of an ischemic stroke
and could reduce death of cells adjacent to the stroke's core
, that were
How the Stem Cells Help Recovery
stem cells used in the trial were multipotent
Interestingly, the dose administered was the largest ever in a human cell
therapy trial. These cells are safe and literally 'off the shelf'
, requiring no
. A single donor can provide several thousand doses to patients
. They were well-tolerated,
and side effects in a few patients included fever, chills, bad breath, nausea
scientists believe that the stem cells operate by modulating the immune system.
An optimal response following any
injury is desirable to ensure healing, removal of dead tissue and debris and
in stroke patients, the spleen,
an important organ of the immune system shrinks in size
. As a result it dumps large quantities of activated immune
into the bloodstream, which could travel to the brain and cause destructive inflammation
phenomenon also causes an immune
leaving the patient susceptible to respiratory
infections and urinary tract infections.
inflammation is good, but in a big stroke, it almost always overshoots,"
Hess said of
second neuroinflammatory response. "We think this secondary
neuroinflammatory process is preventing the natural healing tendencies of the
who received stem cell therapy
were found to have lower blood levels of inflammatory
called cytokines, as well as
other drivers of the immune reaction, including circulating
lymphocytes and a subset of lymphocytes called regulatory T cells.
Future Research Plans
this current phase 2 clinical trial, the research team plans to conduct further
studies in the UK, US,
Europe and Japan as well where there is a significant aging population before
seeking FDA approval.
- They hope to limit the timing of the
therapy to 18-36 hours with centers now equipped with faster means of stem
cell preparation and thawing.
- They plan to measure the spleen size
of the patients before and after therapy
- They also plan to correlate
increased blood levels of cytokines with tissue levels.
- During the phase 2 study itself, the
age limit for giving cell therapy was increased from 79 to 83.
- Also, the
patients included in the stem cell trial was expanded to include patients
who had received both tPA and endovascular clot retrieval rather than one
of the two, since many centers performed clot retrieval.
conclusion, stem cell therapy, if approved for clinical use, could become a
useful adjunct to conventional treatments of stroke.
- David C Hess, Lawrence R Wechsler, Wayne M Clark,
Sean I Savitz, Gary A Ford, David Chiu, Dileep R Yavagal, Ken Uchino,
David S Liebeskind, Alexander P Auchus, Souvik Sen, Cathy A Sila, Jeffrey D Vest, Robert W Mays. Safety and
efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind,
placebo-controlled, phase 2 trial. The Lancet Neurology, (2017); DOI: 10.1016/S1474-4422(17)30046-7