A study involved by the researchers report that development of the endocrine pancreas is promoted by a web like network of epithelial tubes that exist only transiently in the developing embryo. These findings suggest that a deeper understanding of this endocrine differentiation 'niche' could propel development of novel treatments for diabetes. The study has published in Genes & Development.
Researchers group showed that the generation of pancreatic endocrine cells, including the beta cells responsible for producing insulin in our bodies, is promoted by a specialized microenvironment within the embryonic pancreas. Altering this microenvironment can alter endocrine mass. Endocrine cells exist in clusters called "islets of Langerhans." It is these cells that are destroyed or become nonfunctional in diabetic patients.
They discovered that these cells depend on the architecture of their microenvironment and that the weblike network of pancreatic tubes serves as a functional microenvironment for the production of endocrine cells. Previous research has pinpointed this network as the location where an endocrine progenitor cell (stem cell) arises during development.
We altered this microenvironment by deleting Afadin, which is a protein required for tube remodeling. This alteration revealed that increasing the overall volume of these tubes during pancreatic development resulted in an increased mass of endocrine cells, suggesting that these tubes act as a promoter of endocrine cell development.
Pancreatic endocrine cell development has been a major research subject for many years and it has informed studies aimed at generating replacement beta cells, which are the cells that become nonfunctional in diabetes. Endocrine cell deficiency leads to diabetes, which can theoretically be cured by providing functional endocrine cells to patients.
Recent advances in stem cell biology have enabled us to make endocrine-like cells in the lab. However, these cells have thus far failed to do the job and need further improvement to become therapeutically viable. Our work uncovers important characteristics of the birthplace of endocrine cells, and shows that enlargement of this microenvironment induces generation of more endocrine cells.
These findings suggest that lab-made endocrine cells could be improved by developing these cells in a microenvironment that resembles their birthplace. This suggestion is supported by a recent boost in endocrine cell generation when the cells were grown in a 3-dimensional matrix, demonstrating that tissue conformation is influential to proper endocrine expansion and differentiation.
Further studies that employ different approaches to disturb the tube microenvironment and other architectural aspects of the pancreatic progenitor epithelium will be needed to determine their effects on endocrine cell development. By recreating the microenvironment for endocrine cell development in the lab, we may be able to achieve a long-standing goal in diabetes research.
To efficiently produce fully functional glucose-responsive endocrine cells from a patient's stem cells. These cells then could be transplanted back into the patient, and there produce insulin normally.