We are a part of a global community in which the
devastation of spinal cord injury (SCI) bows to no flag, and solutions will
not be any country’s exclusive domain. Integrating the diverse pieces of
the puzzle necessary to develop real-world solutions requires that we
open-mindedly work in cooperation and not in competition. With such
cooperation, restored function after SCI will be a coalescing reality and
not just a never-ending, elusive pie-in-the-sky dream.
In this spirit of bridge-building, I recently
traveled to Moscow, Russia where I became the first American scientist to
check-out an innovative stem-cell program for SCI developed by the
NeuroVita Clinic under the direction of Dr. Andrey Bryukhovetskiy. His
work is especially important because few scientists have accumulated as
much hands-on experience as he has in treating human SCI with stem cells,
an approach many experts believe will play a key therapeutic role in the
I’m always amazed how good often emerges from the
tragic. For example, the Paralyzed Veterans of America (PVA), whose
programs have benefited so many with SCI over the years, was born out of
World War II’s violence. Bryukhovetskiy’s promising stem-cell therapies
also grew out of a desire to help paralyzed veterans, in this case, those
injury in Russia’s Afghan and Chechnya military conflicts.
He is a veteran, specifically a 45-year-old retired
Colonel who once directed the Russian Navy’s neurology department. Because
of his long-standing empathy for paralyzed veterans, Bryukhovetskiy
expressed a desire to collaborate with US veteran organizations, such as
PVA, to accelerate the development of real-world SCI therapies.
Bryukhovetskiy is a charismatic leader passionately
committed to his mission and patients. His work in humans is built upon a
strong foundation of research using a variety of SCI animal models.
Because much of his research has been published in Russian, it is not well
appreciated in the world’s English-emphasizing scientific community. As
seems to be the case for so many innovators regardless of country, he has
often struggled to carry out his pioneering research because the vision
behind it runs counter to more entrenched perceptions of what is possible
Reflecting Hippocrates’ ancient wisdom “that natural
forces within us are the true healers of disease,” Bryukhovetskiy told me
that stem cells “are the medicine within us.”
In 2002, Bryukhovetskiy established NeuroVita, a
state-of-the-art, private clinic that treats a variety of neurological
disorders. The clinic occupies several floors in a wing of the massive N.N.
Blokhin Russian Cancer Research Hospital Complex five miles southeast of
downtown Moscow. Staff includes numerous physicians and rehabilitation
specialists, and has access to the expertise of nearby hospital
scientists. Although to date patients have been treated under an official
scientific research protocol, soon after my visit, the Russian Health
Ministry authorized the use of Bryukhovetsiy’s stem-cell technology for
general clinical practice.
My trip to Moscow went through ten time zones, taking
several days for my luggage to catch up. Because of jet lag and Moscow’s
“white nights” near the summer solstice, it was difficult to sleep at
night but nodding off in the day was common. During my visit, I stayed in
clinic-affiliated lodging. Although few understood English, and the
Russian Cyrillic alphabet makes understanding even more challenging, I was
able to get around with relative ease, e.g., take the subway to the
Kremlin and Red Square, go to the market, etc.
As a reflection of our emerging global community,
television showed, for example, American sitcoms and Arnold Schwarzenegger
movies dubbed in Russian, as well as rock videos featuring Britney Spears,
unfortunately still in English. Although I was unable to talk to waiters,
American rap music was often loudly played in the background. Fortunately,
Bryukhovetskiy’s assistant Maria Zhukova, a former English teacher,
provided excellent translational assistance.
Transplanted Cell Types
Stem cells are progenitor cells that have the
potential to differentiate into a variety of cells that theoretically can
treat various neurological disorders. Bryukhovetskiy has used both
embryonic/fetal and adult stem cells.
Although embryonic/fetal stem cells have the
greatest potential to mature into a variety of cell types, they are
controversial, and it is difficult to direct their differentiation
Adult stem cells are found in many tissues, including
bone marrow, which produces, for example, hematopoietic stem cells that
give rise to blood cells, and nervous tissue, whose stem cells can evolve
into neurons and neuronal support cells (i.e., glia). Although adult stem
cells usually differentiate into the specialized cells associated with the
originating tissue, when certain micro-environmental cues are provided,
they can mature into cells associated with other tissue. For example,
under appropriate circumstances, bone-marrow-derived stem cells have the
potential to become nerve cells.
Certain drugs stimulate the bone-marrow to produce
more stem cells, which then spillover into the blood, where they can be
When the patient is the source of the cells (i.e.,
autologous), there is no immunological rejection when they are
re-introduced. In contrast, embryonic/fetal cells represent different
genetic material (i.e., allogeneic) and have rejection potential, although
to some degree their undifferentiated nature helps minimize this risk.
Bryukhovetsiy no longer uses embryonic/fetal
stem cells due to the ethical controversy surrounding their use, their
rejection potential, and, most importantly, his belief that autologous,
adult stem cells are more effective.
In some patients, Bryukhovetskiy has transplanted
autologous olfactory ensheathing cells (OECs) using procedures developed
by England’s Dr. Geoffrey Raisman. Although not technically stem cells,
OECs have considerable regeneration potential and have been the focus of
much attention in the SCI research community. When OECs are transplanted
into the injured spinal cord, scientists theorize that these cells promote
axonal regeneration by producing insulating myelin sheaths around both
growing and damaged axons, secreting growth factors, and generating
structural and matrix macromolecules that lay the tracks for axonal
Improvement was evaluated using a variety of
assessment procedures, including the commonly used ASIA (American Spinal
Injury Association) impairment scale in which grade A and E represents the
most and least severe injury, respectively. Although this scale is
frequently used, experts emphasize it is often insensitive to small but
significant functional improvements. Bryukhovetsiy has noted this
insensitivity in his research; i.e. some of his patients with very real
life-enhancing improvements did not improve their ASIA grade. Other
measurements included FIM (Functional Independence Measure), which
assesses dysfunction in daily-living activities; various
electrophysiological tests designed to assess neuronal conduction;
magnetic resonance imaging (MRI); and urodynamic testing for bladder
Embryonic/Fetal Cells: In 1996, the Russian
Health Ministry authorized Bryukhovetskiy to carry out limited clinical
trials in SCI. In these early trials, stem cells, neurons, and glia
obtained from a various tissues, including 12-week-old human fetuses, were
transplanted into the spinal cord/fluid of 17 patients with SCI. Their
ages ranged from 16-52 (average 30) years, and the time interval between
injury and transplantation ranged from 1-20 (average 5) years. Six, ten,
and one had cervical, thoracic, and lumbar injuries respectively. In
addition to cell transplantation, all had a variety of other procedures
performed depending upon their unique injuries.
Before treatment, 14 subjects were ASIA grade A and
three were grade B. After transplantation (0.5 - 3-year follow-up period),
four were grade A, five grade B, and seven grade C. Fifteen had some
sensory improvement, seven had motor improvement, and 12 had improved
SpheroGel & Autologous Cells: Bryukhovetskiy’s
team has implanted SpheroGel (a biodegradable polymer matrix) with
embedded cells in six patients who required reconstructive surgeries. In
three, hematopoietic stem cells were embedded, and, in the three others,
olfactory cells. At follow-up (3-8 months), two grade-A patients had
improved to grade C, and one had advanced to grade B. In one patient
(grade B initially), there was no improvement.
Intrathecal Stem-Cell Transfusion: The
intrathecal transfusion of autologous hematopoietic stem cells is the
procedure most currently used. In this relatively straight-forward
procedure involving no surgery, the patient’s stem cells are collected
without anesthesia and stored with viability until they are transfused
back into the patient.
To stimulate hematopoietic stem-cell production and,
in turn, cell accumulation in the blood, patients typically received eight
subcutaneous injections over four days of granulocytic colony-stimulating
factor, a drug also called Neupogen® or Filgrastim. On day
five, the patient is hooked up to a blood separator. Over 3-4 hours, blood
is drawn from a vein; processed by the separator, which isolates the stems
cells; and returned through another vein.
The collected stem cells are concentrated by
centrifugation and slowly frozen in liquid nitrogen (-170o
centigrade) in the presence of dimethyl sulfoxide (DMSO), a
cryopreservative that allows cells to be frozen with minimal damage. Care
is taken to check for infections so that they will not be later introduced
behind the protective blood-brain barrier during transfusion.
At the time of transfusion, the stem-cell suspension
is thawed and about 5.3-million cells injected intrathecally into the
subarachnoid space (i.e., into the spinal fluid) through a L3-L4 lumbar
puncture using a local anesthetic. The procedure, which I observed, is
quick and straightforward. The patient can repeat the transfusion in two
months. Bryukhovetskiy believes multiple transfusions enhance functional
In contrast to hematopoietic stem cells, positive
results have been limited with the intrathecal transfusion of olfactory
cells, previously isolated and cultured from the patient’s nasal tissue.
Although Bryukhovetskiy’s team has collected stem
cells from about 120 patients, for a variety of reasons, including the
presence of latent infections, only about 60 have had cells reintroduced.
Of these 60, 18 have had the recommended multiple transfusions. In turn,
61% of the 18 showed some functional recovery, in some cases dramatic.
Because most patients’ transfusions were relatively
recent, it is too early to assess long-term benefit. Early improvements
are unlikely caused by comparatively slow neuronal regeneration processes
and are probably triggered by altering the injury site’s environment
through the secretion of growth factors and other molecules.
For more scientifically inclined readers,
Bryukhovetskiy hypothesizes that the stem-cells’ regenerative effects are
mediated through an important growth factor called ciliary neurotrophic
factor (CNTF) and its interaction with a key transmembrane receptor
called gp130. This interaction, in turn, influences cell
Like others who are developing function-restoring
therapies, Bryukhovetskiy strongly believes that improvement after
treatment depends upon the patient’s commitment to aggressive physical
rehabilitation designed to maximize restored function. Basically, if
muscles have been disconnected from brain control for many years, it’s
going to take some real work to build up nascent connections. As such, his
clinic emphasizes diverse rehabilitation modalities, ranging from
aggressive exercises to passive massage and acupuncture therapy.
I had the opportunity to interact with a number of
NeuroVita patients. Because their treatments have been relatively recent,
accrued improvements have been generally modest.
Vladimir, a 40-year
old Russian living in Spain, sustained a thoracic T6 complete injury from
a 2001 car accident, and started a series of stem-cell transfusions late
last year. He believes that these recent transfusions, combined with
extensive physical therapy, has resulted in additional leg movement,
including the ability to walk in a swimming pool.
An articulate 19-year-old
Russian living in Bulgaria, Dmitri sustained a cervical C5-6 injury
in a 2000 skiing accident. He has had three transfusions since the
beginning of 2005 and has noted new sensation and sweating. He had some
slight headaches soon after the transfusions.
From Dagestan, Baziat,
21, sustained a T9-11 injury when she was 19. After four transfusions, she
has regained additional leg and hip function.
Alexey, 32, traveled
in from the distant Kamchatka Peninsula on Russia’s far eastern Pacific
side, much closer to Alaska than Moscow. He shared with me the challenges
of living with a severe physical disability in a remote, almost
frontier-like area of Russia. Sustaining a T-8 gunshot injury 11 years
ago, he received his first transfusion last year and was scheduled to
receive his third during my visit. He has acquired more bladder and bowel
function and has increased leg strength and tension.
Olga, 17, sustained
a T8-9 injury seven years ago from an accident. Last year, cell-containing
SpheroGel was implanted in the 4-cm gap in her spinal cord. Since then,
she also has had six intrathecal transfusions. Olga indicated some
increased lower-back strength and improved “inner sensation.”
A year after injury,
another Olga had the 5-cm gap at her T12-injury site filled with
SpheroGel embedded with regenerative cells. About a year after surgery,
she suddenly started gaining some dramatic improvement, which she
demonstrated to me in NeuroVita’s rehabilitation facility.
These are just the patients that I met. For
those interested in further patient feedback, the clinic has developed a
DVD with English subtitles that includes interviews with other NeuroVita
Although by itself probably not an end-all SCI
panacea, this Russian stem-cell therapy is an exceedingly important piece
of the puzzle that brings us ever closer to our overall goal of restored
function after injury. Hopefully, American scientists can open-mindedly
establish collaborations with Bryukhovetskiy so that Americans with SCI
can more readily benefit.
Although Bryukhovetskiy’s work is of paramount
importance, when discussing hot scientific topics like stem-cell therapy,
it is easy to lose track of the fact that it is the patient who
ultimately counts, not the science. In science’s cold objective eye, the
patient becomes a research subject characterized by an impairment-scale,
etc, and whose subjective opinions are often left in the dust of our quest
for scientific purity.
I was grateful for the opportunity to interact with
NeuroVita’s patients, appreciating their willingness to share with me not
only their pain and frustration, but their hope, optimism, and belief in
the future. As a somewhat jaded disability-research veteran, their spirit
In this clinic and others throughout the world I have
visited, the face of SCI seems so similar. Often with the support of
devoted parents, youthful patients with great resolve, motivation, and
old-soul wisdom that belies their youth pursue their dreams of recovery
unencumbered with the limited expectations of the past.
In spite of unique injuries, there seems to be a
collective “soul of SCI” in these patients that transcends culture and
country. Although the efforts of innovative scientists, such as
Bryukhovetskiy, are invaluable, the patients are the true pioneers.
They each send forth a ripple of hope that is converging into a powerful
current which will inevitably wash away SCI’s imprisoning walls.
Contact Information: NeuroVita Clinic,
Kashirskoye Avenue 23A, Moscow, Russia; firstname.lastname@example.org or
Adapted from article appearing in September 2005 Paraplegia News (For subscriptions,
call 602-224-0500) or go to www.pn-magazine.com).