1型糖尿病,细胞替换疗法 z-bo 2020-09-29 412

　　Type 1 diabetes is an autoimmune disease that destroys insulin-producing beta cells in the pancreas. Current cell replacement therapy aims to use human pluripotent stem cells to produce insulin-producing beta cells.

　　In a new study, researchers at the University of Copenhagen in Denmark discovered a signal that determines the fate of immature pancreatic cells or pancreatic precursor cells. They found that in the development of the pancreas, these pancreatic progenitor cells are highly mobile, and their fate is affected by the surrounding environment: contact with certain extracellular matrix components. Determine their ultimate fate. This breakthrough discovery helps to treat type 1 diabetes using pancreatic beta cells produced by stem cells. The extracellular matrix determines the similar fate of pancreatic progenitor cells and stem cells because they can regenerate themselves and differentiate into mature cell types.

　　However, compared with stem cells, their self-renewal ability is usually limited. During organ formation, the dynamic behavior of precursor cells makes it difficult to study. To overcome this obstacle, these researchers implanted human stem cell-derived pancreatic precursor cells on glass slides scattered on different matrix proteins. In this way, it is possible to study how each pancreatic precursor cell responds to the surrounding environment without affecting neighboring cells. Surprisingly, they found that the interaction between different extracellular matrix components changed the mechanical forces in the pancreatic precursor cells. These mechanical forces are produced by the interaction between the extracellular matrix outside the cell and the actin cytoskeleton inside the cell. Pancreatic progenitor cells can produce pancreatic endocrine cells and pancreatic duct cells (duct cells). Pancreatic endocrine cells include all hormone-producing cells in the pancreas, including insulin-producing beta cells and glucagon-producing alpha cells in the pancreatic islets, but pancreatic duct cells are epithelial cells located on the inner wall of the pancreatic duct.

　　In this new study, these researchers showed that exposure to extracellular matrix laminin (laminin) reduces intracellular mechanical forces, thereby instructing pancreatic precursor cells to produce pancreatic endocrine cells. Find. Conversely, exposure to fibronectin increases mechanical forces within the cell, thereby promoting the production of pancreatic duct cells from pancreatic precursor cells. By using this newly identified differentiation mechanism of pancreatic precursors to analyze the differentiation mechanism of pancreatic precursors in detail, these researchers revealed the molecular details of the corresponding signaling pathways. I did it. The results of these studies have physiology to understand the development of the pancreas in the body. Semb’s important role explains: “Many experience-derived substances can be replaced with small molecule inhibitors. These molecules target specific components of this newly discovered mechanical signaling pathway, especially in the current cell differentiation process. The mechanism of action is very It is largely unclear."

　　This new strategy makes it possible to use human pluripotent stem cells to treat diabetes in the future, so that insulin-producing β cells can be produced more economically and reliably. Sam said: "Our discovery opens up new areas to explain how pluripotent progenitor cells differentiate into different cell types during organ formation, and this differentiation process in the laboratory." Provides an opportunity for reconstruction. It can more accurately generate cells that are lost or damaged in serious diseases such as type 1 diabetes and neurodegenerative diseases, and prepare for future cell replacement therapy.