Novocell, Inc., a stem cell engineering company, today announced the development of a process that efficiently converts human embryonic stem cells into insulin-producing pancreatic endocrine cells. The findings are reported in an article appearing on-line today, in advance of print publication, in the journal Nature Biotechnology. Such an approach could provide a means to produce sufficient quantities of insulin producing cells for transplantation into patients with Type 1 diabetes, a treatment that offers a potential therapy for this disease.
Novocell researchers report in the article a differentiation process that successfully engineers human embryonic stem cells (hESCs) into endocrine cells capable of producing insulin as well as other pancreatic endocrine hormones glucagon, somatostatin, pancreatic polypeptide and ghrelin. The in vitro differentiation process mimics normal pancreatic development in the body.
"The efficient, reproducible production of human embryonic stem cell- derived, insulin-producing endocrine cells through a process that mirrors the development of human pancreatic cells represents a critical step toward providing a renewable source of cells for diabetes therapy," said Emmanuel Baetge, Ph.D., chief scientific officer of Novocell and senior author of the publication. "This provides a foundation upon which we can build a standardized process for generating functional insulin-producing cells for the treatment of diabetic patients."
The first step toward generating the insulin-producing cells requires engineering hESCs into definitive endoderm, the gatekeeper cells necessary for formation of the endoderm lineage, including liver, thyroid, parathyroid, lungs, stomach, intestine and pancreas, a process that Novocell reported in Nature Biotechnology in December 2005. From the definitive endoderm, the cells are sequentially matured into foregut endoderm, pancreatic endoderm and endocrine precursors to become pancreatic endocrine cells. The insulin- producing cells contain high levels of insulin similar to levels found in adult human islets. Sugar induced secretion of insulin in the hESC-derived endocrine cells is low, similar to that seen in early human islets. However, these cells are capable of secreting insulin in response to numerous agents, indicating that they have many of the important characteristics of functional beta cells.
Pancreatic islet cells are destroyed in patients with diabetes, and these patients require regular insulin treatment. The transplantation of donor- derived human islets, combined with chronic immunosuppression, has been demonstrated to be an effective therapy for the treatment of diabetes. However, the limited availability of donated pancreatic islets and the adverse side effects of long-term immunosuppression make this type of replacement therapy unsuitable for the general diabetic population, thus limiting its utility.
In addition to generating sufficient amounts of insulin-producing cells from hESCs, Novocell has developed a process by which such cells could potentially be delivered to patients without the need for chronic immunosuppression. The Company’s cell encapsulation technology provides a protective, biocompatible coating for cells that shields them from the immune system, thus allowing them to be more readily accepted in the body without the chronic use of immunosuppressive drugs. Novocell is currently conducting human clinical trials examining the safety and efficacy of subcutaneous implants of encapsulated human primary islet allografts in patients with Type 1 diabetes of long standing duration.
"We anticipate that the combination of our stem cell-generated insulin producing cells with our cell encapsulation technology will provide a treatment option eliminating the two principal barriers precluding widespread application of cell replacement therapies — a limited cell source and immunosuppression," said Alan J. Lewis, Ph.D., president and chief executive officer of Novocell. "Such an approach could truly transform diabetes treatment and greatly reduce medical costs associated with current insulin administration as well as the number of additional drug treatments used to reduce side effects associated with this devastating disease."
About Diabetes
Type 1, or insulin-dependent diabetes occurs when the pancreas ceases to produce insulin due to an autoimmune response that causes the selective destruction of insulin producing cells. People with Type 1 diabetes must take daily insulin and are candidates for pancreatic islet cell transplantation, which provides the potential to treat the disease. The disease is most common in children and young adults, accounting for approximately 10 percent of diabetes cases. The Juvenile Diabetes Research Foundation estimates that more than 1.1 million people suffer from Type 1 diabetes in the United States alone. Additionally, approximately 30 percent of people with Type 2 diabetes require insulin therapy and could potentially benefit from islet cell transplantation.
About Novocell
Novocell, Inc. is a stem cell engineering company with research operations in San Diego and Irvine, CA, and Athens, GA, dedicated to creating, delivering and commercializing cell and drug therapies for diabetes and other chronic diseases. Novocell has three primary technologies: stem cell engineering, cell encapsulation and drug discovery. The Company was founded in 1999 and merged with CyThera and BresaGen in 2004. For more information, please visit http://www.novocell.com.
