In my search
for function-restoring therapies for spinal cord injury (SCI) or
dysfunction, I’ve visited numerous cell-transplantation programs
emerging throughout the world. As a continuation of these efforts, I
recently traveled to China to check-out Beike Biotechnology’s
stem-cell program. An UK’s Times newspaper article selected Beike
(pronounced Bay-Ka) as a runner-up company on its list of the “Top 10
Chinese firms that will challenge the west.” (March 9, 2008)
Beike
Beike was founded in 2005 with funding from Beijing
University, Hong Kong University of Science
and Technology, and Shenzhen City (near Hong Kong), and nurtured with
Chinese government grants. The company has established collaborations
with 60+ scientists at leading Chinese universities. Building upon a
base of research starting a decade ago, Beike-affiliated doctors treated
their first patient in 2001; and in several years, had treated hundreds
with a variety of disorders. As confidence grew, they established Beike
to treat patients with stem cells on a commercial scale.
Since then (12/08), they have treated ~3,900
patients at about 30 clinics in China and one in Thailand, about 800 of
which came from 35 other countries. Over a third of the patients had
spinal-cord dysfunction, including SCI (1176), MS (103), and ALS (194);
and 77 had traumatic brain injury.
Technically, however, Beike does not treat
patients. Through their 18 laboratories located throughout China, the
company provides stem cells to collaborating hospitals. It is the
hospitals who have been granted the authority from the China Ministry of
Health to treat patients in Beike-established clinics. Although many
Chinese hospitals provide stem-cell therapy, Beike is the country’s
largest stem-cell source. Overall, stem-cell therapy is much more
accepted in China. For example, is not uncommon for the more connected
to periodically “shoot-up” with stem cells for rejuvenation sake.
To make the therapy more internationally
accessible, Beike will be establishing laboratories and treatment
centers in India, Europe, Middle East, and either Panama or Mexico.
Visit to Clinics
My multi-city visit was hosted by Beike’s Director
of International Affairs, Jon Hakim, who grew up in my home state of
Minnesota and whose father had been a physician at various Minnesota
hospitals and had treated Vice President Hubert Humphrey. Jon’s
heartland background combined with his Mandarin fluency and Chinese work
experience minimized the cultural gap. In addition, many Chinese doctors
and scientists knew some English from working abroad. As author Marshal
McLuhan predicted, we have, indeed, become a “global village.”
I was astonished by China’s continued growth and
development since my last visit in 2001. Much of the country seemed to
be a high-rise construction zone; expressways were clogged with
stop-and-go traffic; and shoppers scurry around buying Christmas gifts.
I visited Beike clinics in three cities, Qingdao,
Hangzhou, and Shijiazhuang, as well as Beike-affiliated scientists in
Beijing. Of these clinics, Americans tended to go to either Qingdao or
Hangzhou. Eventually, however, patients will be assigned to clinics
based on the specific disorders the clinics are most proficient in
handling.
The clinics were located in a wing or floor of a
collaborating hospital. The suite-like rooms were spacious and modern
(e.g., flat screen TV’s, DVD players, Internet access, etc.) with beds
for caregivers. In each clinic, liaisons fluent in English helped
patients with their needs.
Because
Chinese names can be confusing for Westerners, staff usually adopted a
Western moniker. For example, the Hangzhou clinic patient liaison was
Rebecca, a recent English-literature major (photo with author). The
Shijiazhuang liaison was Stanley, who had worked for a Mediterranean
cruise ship line.
By the Yellow Sea, Qingdao hosted the 2008
Olympic sailing events. Its downtown strip
was
a Chinese “Riviera” with beaches, fancy restaurants, and luxury
shopping. The city is the home of China’s famous Tsingtao beer (a
western derivation of Qingdao), a German-recipe brew that came out of
the 19th century German occupation of the city. The clinic
itself is located in a hospital further out near the airport (Click on
thumbnail). Shops and restaurants under construction by the hospital
will provide opportunities to do nearby activities.
South of Shanghai, Hangzhou is a prosperous,
modern city with beautiful lakes and natural scenery. It is visited by
many Westerners.
Because
Hangzhou is further south, the city is warmer in the winter. The
Hangzhou clinic had a good ambience that fostered patient interactions
and was close to shops and restaurants.
About 200-miles southwest of Beijing,
Shijiazhuang is a more industrial city that greatly grew after the
founding of the People’s Republic of China in 1949, and, until recently,
has been off the beaten track for Westerners. Clinic patients were
primarily from Eastern Europe, the Middle East, India, South America,
and Australia. Beike staff generally picked up patients at Beijing’s
just-built international terminal, a four-hour drive away.
For readers interested in clinic life, check out
the numerous patient blogs posted on
www.stemcellschina.com.
Stem-Cell Review
Stem cells encompass a continuum of cell types that
transform into our end-product tissue. As our central nervous system
(CNS) develops, embryonic stem cells evolve into more specialized
tissue-specific, neural stem cells. Adult stem cells are found in most
tissues, including, for example, CNS, bone marrow, skin, intestine,
liver, muscle, hair follicles, and even teeth. Sometimes, they are
robustly expressed, such as the bone-marrow’s ongoing production of
blood-cell-replenishing stem cells; in other tissue, they are quiescent.
Transplantable cells can be obtained from the
patient (called autologous); genetically different individuals, embryos,
or umbilical cords (allogeneic); or different species (xenogeneic). All
three types have been implanted by various programs to restore function
after SCI. Because autologous tissue is patient derived, there is no
immunological rejection. The undifferentiated nature of embryonic and,
to a lesser degree, umbilical cells also minimizes rejection.
Donor cells are transplanted back into the patient
by a variety of routes, including into the spinal cord or surrounding
fluid, intravenously, or intramuscularly. Although it’s easier and safer
to inject cells into a muscle, blood, or spinal fluid than surgically
accessing the cord, it may not be as effective. Many
devil-is-in-the-details questions remain regarding the ultimate
deposition, fate, and survivability of stem cells transplanted by
divergent routes.
With SCI, it is unclear how functional improvements
are physiologically mediated. The implanted stem cells may become new
neurons or support cells; or alternatively, secrete growth factors or
other substances that augment the function of surviving neurons, or
create an environment more conducive for regeneration.
Commercialization
Many stem-cell programs have grown beyond their
more altruistic, academic research roots and have become economically
driven. Without a doubt, there is big money to be made in stem cells,
which is not necessarily bad. Like all biotech and pharmaceutical
company products, such economic motivation is needed if real-world,
stem-cell therapies are to emerge. Nevertheless, at this stage, caveat
emptor for individuals considering any stem-cell program. Prospective
clients should carefully weigh potential treatment pros and cons
relative to their unique situation, including costs.
Beike stresses upfront that no benefits may accrue;
clients should have realistic expectations. Because every injury and
person is different, responsiveness to any therapy, stem cell or
otherwise, varies considerably.
Beike Stem Cells
Beike transplants a variety of stem cells by
different routes. Frequently, the company uses umbilical cord stem
cells, in part, because cord blood is commonly collected after birth by
Chinese blood banks. Beike also transplants stem-cells obtained from the
patient’s bone marrow. Cells are usually transplanted either
intravenously or by lumbar puncture, the latter which introduces the
cells directly into the CNS. Occasionally, cells have been implanted
directly into the spinal cord.
After testing for diseases, the cord blood is
transferred from the blood bank to a Beike laboratory and retested. Stem
cells are separated from blood cells and platelets through
centrifugation and then cultured in a media containing growth factors,
which enhance rejuvenation potential. The growth media is washed away,
leaving the desired stem cells. To ensure viability, all stem-cell
preparations are fresh and not frozen for later use.
Typically, patients receive 4-7 stem-cell
injections over a 25-35 day period. This treatment regimen is
supplemented with individually tailored, rehabilitation programs.
SCI
Many Beike-treated patients with SCI have regained
life-enhancing benefits, ranging from the subtle to fairly dramatic.
Cumulatively, even little gains have made a big difference in
post-treatment quality of life. In addition to the stem cells, some
improvement is probably due to the patients’ concomitant initiation of
aggressive physical rehabilitation.
Although improvements with some disorders may fade
over time, SCI gains seem to be enduring. Consistent with more long-term
physiological mechanisms, benefits often slowly kick-in after stem-cell
treatment and returning home. Functional gains seem to be greater for
individuals who have been injured for longer periods of time.
Study: Beike scientists have evaluated the
effects of treating 500 patients with umbilical-cord-blood stem cells
(465 completed the study). Patients were 18-65 years old, 78% were men,
and all had been injured 1-10 years before treatment (C4-T10 injuries).
Patients received 4-5 intrathecal injections containing 10-30 million
stem cells at one-week intervals and followed for a year using several
evaluation parameters, including commonly used ASIA assessments
(American Spinal Injury Association) for motor function and sensation.
Statistically significant, modest improvements were documented which
continued after the final injection. No serious side effects observed.
Based on the findings, Beike investigators will
soon be initiating in India a more rigorously designed, randomized,
placebo-controlled trial.
Patient Experience
Beike has treated more patients with SCI than any
other disorder. Many of the patient experiences are posted at
www.stemcellschina.com, including before-and-after-video
documentation.
For illustrative purposes, I’ve included Gabi’s
experience. A 30-year-old Romanian, who was one of Beike’s first foreign
patients, Gabi sustained a C5-6 incomplete injury in 1995 from a diving
accident. After three sets of stem-cell injections, Gabi posted the
following [English edited]:
“My hand movements are
much better. I have more power in my hands and body, and new sensations
all the way down to my feet, almost 90% … I feel my hands 100% now.”
“I’ve started to move my
fingers a little and can feel pain in my first two fingers. I also can
feel a lot of heat in my legs, and…can move my feet, but only 1-2 times.
Now, I can contract my stomach muscles. I can stay on my feet 30-50
minutes, but with assistance and support on my knees. I have more
stability than before, and when I’m on my feet I can move my hands and
body more because my abdominal and back muscles are stronger.”
When lying in bed, I can move my feet a little … I can hold my urine for
5-10 minutes before I have to go. My sensation is much improved; I can
feel better my legs and all my body for temperature, as well as pain and
touch (skin) sensation…My stability is much better than before, I can
sit on the bed without support, and if my mother pushes my legs forward,
I can move them back. So, now I have started to move my legs; even if it
is a little, it’s a start. My triceps have started to work too.”
Patients I specifically met during my visit
included Cheryl who sustained a T12 complete injury five years earlier
from falling off a horse; and Leslie who was injured 12 years previously
from a diving accident. Both had returned to China for a second set of
treatments and have patient blogs.
Cheryl
reported improvements in bowel and bladder function, and muscle control
and sensation in legs. Leslie had a considerable reduction in the
chronic pain that had plagued her since injury. (Photo: Leslie with
author, mother, and clinic doctors)
Conclusion
A recent article in a scientific journal noted that
beneficial claims promoted over the internet by many stem-cell clinics
represent over-hyped, economically driven marketing and are not
supported by sufficient peer-reviewed studies. Although I agree with
many points, the article demonstrated one of the scientific community’s
quintessential weaknesses: the authors didn’t bother to talk to any
patients. Essentially, the authors just relied in one form or another on
the opinions of like-minded Western scientists (i.e., another definition
of peer review).
Although people with SCI are demanding real-world
solutions now, scientists believe the best way to develop these
solutions is an allegiance to what many with SCI consider a glacial,
trickle-down scientific process. Through searching the internet, people
with SCI increasingly get glimpses of what is possible and don’t want to
wait until science’s liaise-faire approach produces a thumbs-up approval
at some distant point in the future.
It doesn’t have to be like this. If we are
flexible, there are ways to reduce the scientific and regulatory hurdles
to speed-up the development of safe and efficacious approaches for
restoring function after SCI. One of the easiest is to open-mindedly
establish bridge-building collaborations with investigators, programs,
or clinics in other countries.
Adapted from article appearing in March 2009 Paraplegia News (For subscriptions,
call 602-224-0500) or go to
www.pn-magazine.com.
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