September 2003 - When researchers at Washington University School of Medicine in St. Louis transplanted early embryonic pancreatic tissue into the abdomens of adult rats with type I diabetes, the animals developed organs that produced insulin and controlled blood-sugar levels. The animals were cured of their diabetes for the duration of the experiment, which lasted 15 weeks.
"The transplanted tissue developed into a totally novel organ," says lead scientist Marc R. Hammerman, M.D., the Chromalloy Professor of Renal Diseases in Medicine. "It's a pancreas that produces insulin but lacks the components that secrete digestive enzymes."
The investigators' work is directed toward developing a new treatment for type 1 diabetes mellitus, also known as juvenile diabetes. The findings are published in the September-October issue of the American Society for Artificial Internal Organs Journal.
Type 1 diabetes mellitus is one of the most common chronic diseases in children and adolescents in the United States. Between 10,000 and 15,000 new cases are diagnosed annually, and there are about 1 million afflicted adults. Self-administered daily insulin injections are the mainstay of treatment, but they cannot prevent the long-term complications of the disease.
Type 1 diabetes also can be treated by transplanting whole pancreas or isolated insulin-producing pancreatic cells, so-called islet cells. But the supply of human organs for transplant falls far short of the need, and transplanted islet cells tend to survive only for short periods.
"Theoretically, the shortage of human islets could be overcome through use of islet tissue derived from animals such as pigs," notes Hammerman, who also directs the Renal Division at Washington University School of Medicine and Barnes-Jewish Hospital. "Unfortunately, the limited research on pig-to-human islet transplantation suggests that even large quantities of transplanted islets do not cure human diabetes."
Hammerman and Sharon Rogers, research instructor in medicine, and Helen Liapis, M.D., associate professor of pathology and immunology, removed the early pancreas from developing rat embryos less than one day after the organ began to form. They transplanted the tissue into mature rats with type I diabetes. Unlike adult pancreatic cells, embryonic cells divide repeatedly after transplantation to produce small masses of insulin-producing tissue.
Two weeks after transplantation, the embryonic tissue had grown and begun making insulin. Within five weeks, the transplanted tissue produced enough insulin to maintain normal blood-sugar levels in the diabetic animals.
Hammerman and Rogers transplanted the primitive pancreatic tissue using techniques they had developed over the past five years to grow new kidneys in animals with failing renal function by transplanting embryonic kidneys. Their previous research showed that they could reduce rejection of transplanted tissues by using very early embryonic organs instead of adult tissue.
"Embryonic pancreas has been transplanted before, but never in quite this way," Hammerman says. "Our method seems very promising."
Rogers SA, Liapis H, Hammerman MR. Intraperitoneal transplantation of pancreatic anlagen. American Society for Artificial Internal Organs Journal. 49:527-532, Sept./Oct. 2003.
Funding from the Renal Division at Washington University School of Medicine in St. Louis 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.
Source: Washington University School of Medicine