(Once again adding credibility to 'all men are pigs')
'Major obstacle' overcome in diabetes research
By Caroline Arbanas
With an eye on curing diabetes, School of Medicine scientists have
successfully transplanted embryonic pig pancreatic cells destined to
produce insulin into diabetic macaque monkeys — all without the need
for risky immune suppression drugs that prevent rejection.
Marc Hammerman
The transplanted cells, known as primordia, are in the earliest
stages of developing into pancreatic tissues. Within several weeks of
the transplants, the cells became engrafted, or established, within
the three rhesus macaque monkeys that received them. The cells also
released pig insulin in response to rising blood glucose levels, as
would be expected in healthy animals and humans.
"The approach reduced the animals' need for insulin injections and
has promise for curing diabetes in humans," said senior investigator
Marc Hammerman, M.D., the Chromalloy Professor of Renal Diseases in
Medicine. "The transplants worked without a need for immune
suppression, and that is a major obstacle we have overcome."
The researchers' results appear online and are published in the
journal Xenotransplantation
Although the transplants fell short of producing sufficient insulin
to cure the macaques' diabetes, Hammerman predicts that with
additional research, including the transplantation of additional
embryonic pig cells into the animals, he will be able to reduce the
macaques' need for insulin injections entirely.
The new research follows on the heels of reports by Hammerman and his
colleagues demonstrating that transplanted pig pancreatic primordia
can cure both type 1 and type 2 diabetes in rats without using immune
suppression drugs. Other scientists have tried different types of
pancreatic cell transplants — in animals and humans — as a
steppingstone to curing diabetes, but they all require anti-rejection
drugs. These drugs must be taken daily to stave off rejection and
have adverse effects that limit the success of the transplants.
As a treatment for diabetes in people, pig insulin typically works as
well as the human form. Before recombinant DNA technology enabled
pharmaceutical companies to manufacture human insulin in the 1980s,
pig and cow insulin were routinely given to diabetic patients.
The primates in the current study had type 1 diabetes, the form that
occurs when islet cells in the pancreas stop producing insulin
altogether. The WUSTL researchers transplanted 19 embryonic pig
pancreatic primordia into each diabetic monkey. Each primordium is
smaller than the diameter of a period that ends a sentence and is
transplanted into a membrane that envelops the intestines and other
digestive organs.
The transplanted cells were retrieved from the pig embryos early in
their development, which is believed to render them "invisible" to
the primates' immune system or induce a state of tolerance, either of
which eliminates the need for immune suppression.
The researchers determined by multiple methods that the transplanted
cells became established within the primates. And as the cells
matured, they began to release pig insulin.
"We found using every method that the cells engraft long-term and,
thus, are not rejected by the animals' immune systems," Hammerman
said. "It's been more than two years since our first transplant was
carried out. That particular primate doesn't produce any primate
insulin but has pig insulin circulating in its bloodstream that has
reduced by more than 50 percent the amount of injected insulin the
animal needs compared to levels before the transplant. The animals
have never received immune-suppression drugs."
Two of the macaques remain healthy. One, however, became anemic about
six weeks post-transplant and was euthanized a month later after
developing acute respiratory distress. The researchers could not find
a link between this animal's illness and the pancreatic cell
transplants. The two remaining macaques have each received two
transplants of embryonic pancreatic cells. One of the animals has
been followed for 23 months after his first transplant, and the
amount of insulin he needs to have injected has declined by 55
percent over baseline levels. The other macaque has been followed for
10 months after his initial transplant, and his need for injected
insulin continues to decline.
Hammerman and his colleague Sharon Rogers, research instructor in
medicine, are leaders in the emerging field of organogenesis, which
focuses on growing organs from transplanted embryonic organ
precursors known as primordia. Unlike embryonic stem cells, which can
become virtually any cell type, primordia are locked into becoming
cells of a particular organ.
"We are encouraged by these results," Rogers said. "The absence of a
need for immune suppression in diabetic rats gave us hope that we
were on the right track. But many findings in rats do not hold true
for species that are more closely related to humans, such as nonhuman
primates. This one did."
The team will now determine how best to eliminate the need for
injected insulin in the diabetic macaques that receive transplants,
thus demonstrating long-term effectiveness of the technique, and
establish the safety of pancreatic primordia transplants. If these
experiments succeed, the researchers plan to conduct clinical trials
in humans with diabetes.
"We hope to find out how to apply our findings to human type 1 and
type 2 diabetics because the embryonic pig primordia would represent
an unlimited source of tissue for transplantation,
http://record.
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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