Chinese researchers have become the world's fifth most prolific
contributors to peer-reviewed scientific literature on
clock-reversing regenerative medicine even as a skeptical
international research community condemns the practice of Chinese
clinics administering unproven stem cell therapies to domestic and
foreign patients.
According to a study by the Canadian-based McLaughlin-Rotman
Centre for Global Health (MRC), published today by the UK journal
Regenerative Medicine, China's government is pouring dollars
generously into regenerative medicine (RM) research and
aggressively recruiting high-calibre scientists trained abroad in
pursuit of its ambition to become a world leader in the field.
And its strategy is working: Chinese contributions to scientific
journals on RM topics leapt from 37 in year 2000 to 1,116 in 2008,
exceeded only by the contributions of experts in the USA, Germany,
Japan and the UK.
The accomplishment is all the more astonishing given that
China's international credibility has been and still is severely
hindered by global concerns surrounding Chinese clinics, where
unproven therapies continue to be administered to thousands of
patients.
New rules to govern such treatments were recently instituted but
need to be strictly enforced in order to repair China's global
reputation, according to MRC authors Dominique S. McMahon, Halla
Thorsteinsdóttir, Peter A. Singer and Abdallah S. Daar.
They drew their conclusions after having gained unprecedented
access to almost 50 Chinese researchers, policy makers, clinicians,
company executives and regulators for interviews. The research was
made possible by funding from the Canadian Institutes of Health
Research.
"When you look at the issue of stem cells in China, you see the
Yin-Yang of a scientific powerhouse mixed with controversial
clinical application of stem cell therapies," says Dr. Singer,
MRC's Director. "The overall picture at the moment is ambiguous but
in the future, given the measures that have been put in place, the
science can be expected to rise and the controversy to fall."
Regenerative medicine an interdisciplinary field of research and
clinical applications focused on the repair, replacement or
regeneration of cells, tissues or organs to restore impaired
function resulting from any cause, including congenital defects,
disease, trauma and aging. It uses a combination of several
converging technological approaches, both existing and newly
emerging, that moves it beyond traditional transplantation and
replacement therapies. The approaches often stimulate and support
the body's own self-healing capacity. These approaches may include
the use of soluble molecules, gene therapy, stem cell transplants,
tissue engineering, and the reprogramming of cell and tissue
types.
MRC researchers report that until May 2009 clinical trials to
determine the effectiveness of stem cell therapies were not
required. Now proof of safety and efficacy through clinical trials
is required by China's Ministry of Health for all stem cell and
gene therapies.
The change was made after international experts, joined by top
Chinese researchers, protested that treatment centers were acting
"against commonly accepted principles of modern scientific
research" and successfully called on China to regulate new
treatments and ensure patient safety.
Despite the new rules, however, stem cell treatments are still
available at over 200 hospitals across China to patients of
diseases such as ataxia, Lou Gehrig's disease, traumatic brain and
spinal cord injury, diabetes, Parkinson's, multiple sclerosis,
autism, cerebral palsy, stroke, optic nerve hypoplasia and many
others.
"To our knowledge, Chinese policy makers and ethicists are
working out the regulation details,” says Ms. McMahon, the
study's lead author. "Once that is accomplished, we still expect a
delay, during which the therapies currently administered by clinics
and hospitals will be evaluated individually to determine whether
they meet the criteria of China's Ministry of Health."
"It is hard to say what impact these new clinical regulations
will have in China, although certainly they show the government's
commitment to changing the way things are done," she adds.
Beike Biotechnology Inc. (Shenzhen) is the largest of the
Chinese therapy centers and claims to have treated over 5,000
patients to date, including more than 900 foreigners, offering stem
cell injections into spinal fluid, for example.
The Stem Cell Center affiliated with Tiantan Puhua Neuroscience
Hospital in Beijing, meanwhile, claims to activate and multiply the
body's own neural stem cells through oral and intravenous
medications and rehabilitation. It also offers a lumbar puncture or
brain injection of bone marrow stem cells, fetal neural stem cells,
or other stem cell types to allegedly improve symptoms of stroke,
cerebral palsy, spinal injury, Parkinson's disease or other
neurological diseases.
Controversial stem cell therapies provided at Beijing Xishan
Institute for Neuroregeneration and Functional Recovery, involve
injecting cells from aborted fetuses to treat spinal cord injury
and a variety of central nervous system diseases. About 1,500
patients have received this treatment, including roughly 1,000
foreigners.
MRC authors say this latter stem cell therapy is the only one
discussed in high-impact peer-reviewed academic journals. One study
documented a spinal cord injury patient's early motor and sensory
improvement, another found no improvement in seven spinal cord
injury patients. Another recent publication found the therapy
improved some spinal cord injuries in animals but its effectiveness
in humans "is not yet established."
Despite the absence of randomized clinical trial evidence that
these stem cell therapies work, an "increasingly popular but
controversial" tourism industry has grown up around them.
"This is a matter of international importance, as increasing
numbers of foreign patients travel to China to seek unproven stem
cell therapies not available in their home countries," according to
the MRC. "The International Society for Stem Cell Research (ISSCR)
strongly condemns the administration of unproven stem cell
therapies … and has written a handbook to help doctors and
patients make informed decisions about available stem cell
therapies."
As for advice to last-resort patients considering Chinese clinic
stem cell treatments: "This is not a medical study," says Dr.
Singer. "Instead we urge such patients to consult their own medical
professionals. The International Society for Stem Cell Research has
certainly made their stance clear."
"These therapies are sought out by desperate, no-option patients
seeking marginal improvements in their quality of life. People
should get as much information as possible before committing to any
procedures. Each clinic provides a different therapy for a variety
of different ailments and there is no systematic evidence that
these therapies work."
Chinese firsts
While unorthodox activities at Chinese clinics and controversial
drug approvals have raised eyebrows both in and outside China,
dedicated researchers in the country's labs have been making
remarkable contributions to the field.
Among the country's scientific firsts:
- By transferring the nucleus of a human skin cell into the
immature ovum cell of a rabbit, researchers from a Shanghai
hospital successfully produced embryonic human cells (a finding
popular scientific journals held off publishing for two years due
to skepticism and of mistrust Chinese scientific integrity).
- China to date has created at least 25 human embryonic stem cell
lines (some estimate over 70 stem cell lines), four of which are of
a specialized type that at that time only two other groups
worldwide had managed to create.
- A Shanghai hospital cultivated and reintroduced human brain
tissue in 2002 after taking a sample from the end of a chopstick
implanted in a patient's frontal lobe following a disagreement at a
restaurant.
- Several human tissue types created artificially include blood
vessel, tendon, bone, cartilage, skin, cornea and muscle
fiber.
Notable research underway
Current research of note includes the efforts of ChinaSCINet, a
consortium of 27 medical facilities, starting phase 2 clinical
trials to test the efficacy and safety of using cord blood stem
cells and oral lithium to treat about 40 patients with spinal cord
injuries.
Other clinical trials are underway on the use of stem cell
therapies to treat patients of heart attacks, artery obstruction,
and liver and neural diseases.
Elsewhere in China, studies are underway on the potential use of
stem cells to treat Type 1 diabetes, Parkinson's disease, heart,
liver and blood diseases, eye cataracts, and to combat aging.
Liberal research rules
Guidelines governing Chinese research are liberal but common to
other countries as well.
Chinese regulations prohibit reproductive cloning, the use of
human embryos past 14 days post-fertilization, the fusion of human
and non-human gametes (cells that fuse during fertilization), or
the implantation of research embryos into human or animal
uterus.
Researchers are required to obtain informed consent from
subjects and institutes must have an ethics review board to approve
research involving human embryonic stem cells.
Chinese fertility clinics serve as a source of discarded
embryonic stem cells for some research, and cord blood banks may
serve as a source of stem cells for clinical applications.
Therapeutic cloning is allowed, as is the use of surplus embryos
or discarded fetal cells from abortions as well as embryos created
with artificial help.
"What sets China apart from most of the rest of the world is
that these regulations do not prohibit the fusion of human genetic
material with nonhuman oocytes (cells from which an egg or ovum
develops)," the MRC authors say.
As well, the rules for embryonic stem cell research in China are
criticized internationally as having limited authority over
researchers because they are not legally binding. Adherence is
enforced only for those who receive government funding, which
applies to most researchers, but financially independent
researchers or hospitals must simply answer to their own
institution's ethical review board.
MRC authors say that while there is no indication embryonic stem
cell research rules are being broken, greater regulatory oversight
would help ease international concerns.
Interviewees agreed that regulation enforcement is a key
concern. According to one, a lack of inspection capacity cast doubt
on regulatory implementation.
Huge Chinese investment in RM
Chinese data show the country now generates 400,000 graduates in
science and medicine each year and recruits many high caliber
scientists from abroad.
China’s gross domestic expenditure on R&D in science
and technology has grown from $5.9 billion in 1996 to $44 billion
today. Stem cell research, tissue engineering and gene therapy are
key areas receiving priority funding, largely centralized in the
universities, hospitals and research institutes of China's main
urban centers, especially Beijing and Shanghai.
Approximately 78% of China's R&D funding in RM is reserved
for product development, with an additional 16.8% for applied
research. And China has developed large primate colonies for
preclinical testing, and begun clinical trials for a number of
therapies.
According to the MRC, China's push for clinical applications,
which has allowed it to produce new scientific knowledge quickly,
has come at the expense of basic research aimed at, for example,
overcoming technical challenges such as controlling how stem cells
behave and differentiate.
Only 5.2% of China's budget for research and development is
allocated to basic research, compared with 13 to 19% in Japan,
Korea and the USA. Even the funds allocated for basic research
favor 'strategic basic research' designed to encourage
application.
China's recruitment policy a model for other developing
countries
"China has catapulted itself into the field of regenerative
medicine in a relatively short time," says Dr.
Thorsteinsdóttir. "The government's policy of attracting
highly educated Chinese nationals back to China has contributed
significantly to the country's success in the field."
"I was amazed that almost all the top Chinese researchers the
regenerative medicine field had been educated in the US and the UK
and gained extensive working experience there in cutting edge
research," she adds. "This is a policy other countries lacking
relevant human resources should consider."
"New regulations may in time help restore international
confidence in Chinese stem cell innovations, but it will take time
to evaluate their impact," says Dr. Daar. "The creation of new RM
therapies needs a clear regulatory path. There should also be a
closer connection between applied research and those providing
therapy."
"China is an important player in regenerative medicine," says
Ms. McMahon, "Despite the media's focus on stem cell tourism, the
international community needs to recognize that Chinese researchers
are making important contributions to the science of this field,
and China should be included in international discourses on
standards and regulations."
"Regenerative medicine research in China is a source of national
pride," she adds. "The Chinese rightly feel their research
discoveries can achieve solutions to many global health problems.
If China continues to build on its strengths and overcomes its
challenges, successful, internationally acclaimed regenerative
medicine treatments and therapies are more than likely."
SOURCE