Overcoming the Limitations of Stem Cell-Derived Beta Cells.

Great advances in type 1 diabetes (T1D) and type 2 diabetes (T2D) treatment have been made to this day. However, modern diabetes therapy based on insulin injections and cadaveric islets transplantation has many disadvantages. That is why researchers are developing new methods to regenerate the pancreatic hormone-producing cells in vitro. The most promising approach is the generation of stem cell-derived beta cells that could provide an unlimited source of insulin-secreting cells. Recent studies provide methods to produce beta-like cell clusters that display glucose-stimulated insulin secretion-one of the key characteristics of the beta cell. However, in comparison with native beta cells, stem cell-derived beta cells do not undergo full functional maturation. In this paper we review the development and current state of various protocols, consider advantages, and propose ways to improve them. We examine molecular pathways, epigenetic modifications, intracellular components, and the microenvironment as a possible leverage to promote beta cell functional maturation. A possibility to create islet organoids from stem cell-derived components, as well as their encapsulation and further transplantation, is also examined. We try to combine modern research on beta cells and their crosstalk to create a holistic overview of developing insulin-secreting systems.

Comparative analysis reveals similarities between cultured submandibular salivary gland cells and liver progenitor cells.

Mouse submandibular salivary gland cells and liver progenitor cells from long-term in vitro cultures with a high proliferation potential were side-by-side compared by methods of immunocytochemistry, quantitative real-time PCR, flow cytometry, and transcriptome analysis. The two cell types were found to be similar in expressing cell markers such as EpCAM, CD29, c-Kit, Sca-1, and c-Met. In addition, both cell types expressed cytokeratins 8, 18, and 19, alpha-fetoprotein, and (weakly) albumin. Unlike the liver cells, however, the salivary gland cells in culture showed high-level expression of cytokeratin 14 and CD49f, which was indicative of their origin from salivary gland ducts. Quantitative real-time PCR and deep-sequencing transcriptome analysis revealed similarities in the expression pattern of transcription factors between the two cell types. In this respect, however, the cultured salivary gland cells proved to be closer to exocrine cells of the pancreas than to the liver progenitor cells. Thus, ductal cells of postnatal submandibular salivary glands in culture show phenotypic convergence with progenitor cells of endodermal origin, suggesting that these glands may serve as a potential cell source for cellular therapy of hepatic and pancreatic disorders. The results of this study provide a deeper insight into the molecular features of salivary gland cells and may help optimize procedures for stimulating their differentiation in a specified direction.