|Using a Diabetes Patient’s Own Liver Cells as a Novel Source of Insulin|
|By Sarah Ferber, Ph.D.|
|Friday, 15 June 2012 02:33|
According to the American Diabetes Association, 1.9 million new cases of diabetes are diagnosed in people aged 20 years and older in 2010, an estimated 7.0 million Americans have undiagnosed diabetes, and another 79 million have pre-diabetes. In addition, approximately 25.8 million children and adults in the United States-8.3% of the population-have diabetes.
For years, the concept of harvesting stem cells and re-implanting them into one's own body to regenerate organs and tissues has been embraced and researched in animal models. The treatment being developed by Orgenesis consists of several steps. First, a standard liver biopsy is taken from a diabetes patient in a clinical center and sent to a laboratory. In the lab, the liver cells are first propagated in vitro. Some of these cells are then manipulated with a therapeutic agent (i.e., the "master regulator" PDX-1 that governs pancreas development, or additional pancreatic transcription factors in adenovirus-vector) that converts a subpopulation of liver cells into different cells with pancreatic islet phenotype and function.
The therapeutic agent triggers a cascade of events, converting the cells into "autologous insulin-producing" (AIP) cells. These cells now act similarly to the beta cells that produce insulin in the pancreas of healthy individuals. Insulin is not only produced, but also stored and secreted in a glucose-regulated manner.
Back at the clinical center, the newly formed AIP cells are then transplanted in a standard infusion procedure back to the patient's liver where they secrete insulin. Since the initial liver cells were taken from the patient himself or herself, there is no chance of rejection. Orgenesis has successfully tested its technology in mice, rats and pigs, and is working toward initiating clinical trials in humans.
The surprising capacity to activate pancreatic lineage in the liver was first demonstrated in mice by systemic PDX-1 administration using recombinant adenovirus gene delivery. PDX-1 plays a dual and central role in regulating both pancreas organogenesis in embryo and beta cell function in adults. The capacity of PDX-1 to direct pancreas development has been demonstrated in mature fully differentiated liver in vivo, both in mice and in Xenopus, possibly via a process called trans-differentiation. This describes an irreversible switch of one type of differentiated cell into another differentiated cell.
AIP therapy seems to be safer than other options, as it does not alter the host genome but only alters the set of expressed genetic information that seems to be highly specific to the reprogramming protocol. In addition, no human organ donations or embryo-derived cells are required.
This form of therapy, if proven to be workable in clinical trials, would provide several advantages over other insulin-dependent diabetes therapies currently being studied. First, it frees the patient from daily involvement in the monitoring of blood glucose levels, numerous insulin injections and watching food intake and exercise. Indeed, the body itself is now continuously controlling blood glucose levels. In addition to avoiding the chance of autoimmune rejection, the procedure is only minimally invasive.
In summary, the use of adult human liver cells for generating functional insulin-producing tissue may pave the way to autologous implantations, thus allowing the diabetic patient to be the donor of his or her own insulin-producing tissue.