Pigs, Rats, Primates, Humans?



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Pro-Humanist FR

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Type 1 diabetes research news:

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Feb. 25, 2004 http://www.sciencedaily.com/releases/2004/02/040226064745.htm
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Excerpts:

Embryonic Pig Cell Transplants Halt Rat Diabetes

An experimental cross-species transplant to treat diabetes has passed an early test in rats with better-than-
expected results, suggesting the innovative approach might halt type 1 diabetes while greatly
reducing the risk of rejection.

Scientists at Washington University School of Medicine in St. Louis set up control and experimental
groups of rats with diabetes. The experimental group received embryonic pig pancreas cell
transplants and antirejection drugs to prevent the rats' immune systems from destroying the
transplants. The control group received only the transplants and no im- mune suppression drugs. To
the researchers' surprise, the control group's transplants grew unmolested by the immune system,
halting the rats' diabetes and changing the focus of the study to transplanting without the need for
immune sup- pression.

"Every once in a while you get lucky, and now we have the possibility of transplanting these pig
cells and not having to worry about rejection," says Marc R. Hammerman, M.D. ... Hammerman, an
endocrinologist and director of the Renal Division, is a leader in the emerging field of
organogenesis, which is focused on growing organs from stem cells and other embryonic cell clusters
known as organ primordia. Unlike stem cells, primordia cannot develop into any cell type -- they
are locked into becoming a particular cell type or one of a partic- ular set of cell types that
make up an organ.

In multiple groups of diabetic rats that were unable to pro- duce their own rat insulin, Hammerman
and Sharon Rogers, research instructor in medicine, transplanted pig pancreas primordia into the
omentum, a membrane that envelops the intestines and other digestive organs. Within two weeks, the
primordia engrafted and began producing pig insulin.

The pig insulin replaced the missing rat insulin, returning the rats' blood glucose to normal
levels, an effect that continued for the rest of their lives.

...

Hammerman had theorized for years that implanting primordia obtained very soon after organ formation
and coaxing the cells into growing into fully functioning organs inside a transplant recipient might
reduce immune system rejection. However, he admits he is stunned by the new success.

"Conditions that are permissive for transplantation from one species to another frequently don't
translate to transplants into another species," Hammerman says. "But this dramatic elimin- ation of
the need for immune suppression is quite unusual; there's not a lot of precedent in the literature
for it. So it's pos- sible that it may also apply in other cross-species transplants and maybe even
in pig-to-human transplants."

Diabetes in humans is sometimes treated by transplanting human insulin-producing pancreas cells
known as the islets of Langerhans. According to Hammerman, using embryonic pig cells as the
transplant source instead of human islets circum- vents three major difficulties.

"First, there aren't nearly enough human pancreas organs to go around," Hammerman says. "Since pig
insulin works fine in humans, if pigs could be used as donors the shortage would be alleviated."

Second, islets can only be extracted from the pancreas by mincing the organ and exposing it to
enzymes that break down connective tissue.

"This damages islets," Hammerman says. "So not all of the transplanted islets engraft, and many that
do engraft die after a period of time."

Third, islets are composed of mature cells unable to respond to increased need for their services by
dividing and producing more cells. In contrast, embryonic pancreas cells divide readily in response
to such needs, resulting in a potentially expandable source of insulin.

For reasons not yet understood, the transplanted pancreas cells did not develop an additional
digestive function normally asso- ciated with the pancreas.

"That was another remarkably lucky break," Hammerman notes, "because only the endocrine cells are
required to treat diabetes. The digestive cells would have only caused problems."

If elimination or reduction of immune rejection transfers to pig-to- human transplants, the
technique will defeat or greatly diminish a final formidable obstacle to treating diabetes with
transplants.

"Immunosuppressing a patient introduces a whole new set of dan- gers and side effects," says
Hammerman. "Patients with type 1 diabetes have to ask themselves, would I rather take insulin, or
would I rather take all these immunosuppressive drugs? It's not the greatest choice in the world."

The next phase of research will involve pig-to-primate transplants. If those are successful, then
pig-to-human transplant trials can be considered.

Hammerman also is studying the use of kidney primordia from embryonic pigs to grow new kidneys
inside recipients as a treat- ment for end-stage kidney failure.

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