Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Embryonic pig cell transplants halt rat diabetes

26.02.2004


Procedure requires no immune suppression drugs



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 immune 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 suppression.


"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., the Chromalloy Professor of Renal Diseases in medicine and leader of the study.

The results appear online and will be published in the April issue of The American Journal of Physiology-Endocrinology and Metabolism.

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 particular set of cell types that make up an organ.

In multiple groups of diabetic rats that were unable to produce 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. Failure to gain weight, another characteristic symptom of diabetes, was also reversed following the transplants.

In a final group of transplant recipients, Rogers, Hammerman, Feng Chen, Ph.D., assistant professor of medicine, and Mike Talcott, D.V.M., director of veterinary surgical services, showed that pig insulin-producing cells were present in the omentum and had caused a buildup of fat, a change previously linked to successful engraftment of pancreatic tissue.

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 elimination of the need for immune suppression is quite unusual; there’s not a lot of precedent in the literature for it. So it’s possible 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 circumvents 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 associated 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 dangers 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 treatment for end-stage kidney failure.


Rogers SA, Chen F, Talcott M, Hammerman MR. Islet cell engraftment and control of diabetes in rats after transplantation of pig pancreatic anlagen. American Journal of Physiology-Endocrinology and Metabolism, April 2004.

Funding from the National Institutes of Diabetes and Digestive and Kidney Diseases supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Michael C. Purdy | EurekAlert!
Further information:
http://medinfo.wustl.edu/

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>