After a decade of exploring strategies to develop an alternative supply of insulin-producing cells, researchers have recently focused on two that are the most likely to replace islets for transplantation – or regeneration – and address the critical cell supply shortage.
As published in Trends in Endocrinology & Metabolism, scientists at the Diabetes Research Institute were recently asked to write a thorough review of the progress in both areas and how these developments will benefit those living with type 1 diabetes. Key takeaways from their article are:
• Islet transplantation works for type 1 diabetes, but its clinical application is limited due to shortage of donors and the need to take anti-rejection drugs for life.
• Stem cell therapies are finally coming of age in the context of restoring the endocrine function of the pancreas. Clinical trials aimed at testing the safety and efficacy of human embryonic stem cell-derived islet-like cells are already underway.
• The two strategies most likely to replace islets for transplantation are:
1. Pluripotent stem cells (PSCs) (through directed differentiation) and
2. Pancreatic non-endocrine cells (through directed differentiation or reprogramming).
• If successful, these approaches are expected to lead to the phasing out of the use of donor islets (from cadavers) for transplantation, exponentially increasing the ability to treat millions of people with type 1 diabetes – and potentially also type 2 patients.
• Non-endocrine pancreatic tissue (NEPT) is the part of the pancreas (the exocrine pancreas) that does not contain insulin-producing islets.
• This part of the pancreas, which is usually thrown away after isolating the islet cells (only about 2 percent of the organ), could be converted into endocrine cell types and then transplanted.
• This tissue contains many subpopulations that can be converted into beta cells. In recent studies, these cultured human non-endocrine cells were tested for their ability to be reprogrammed into islets.
• Exposure to BMP-7 led to the generation of insulin-producing islets at a higher levels than other methods where islets where genetically modified.
• If conversion of non-endocrine to endocrine cells could be induced in situ (within the body), then the need for transplantation may be circumvented altogether.
• Conversion encompasses two very different approaches
1. The reprogramming of non-endocrine tissues
2. The stimulation of progenitor cells within the exocrine pancreas.
• Some of the avenues of research could find their way to clinical studies sooner than we expect.
By Dan Trecroci
Trends in Endocrinology & Metabolism
“The Human Endocrine Pancreas: New Insight on Replacement and Regeneration”
Lead Author: Dr. Juan Dominguez-Bendala