Untitled

Abstract

The prevalence of diabetes has been increasing in recent years and become a threat to human health, now a days, islet replacement therapy is a widely accepted diabetes therapy. Tissue engineering, which involves implanting the scaffold compounded with seed cells and biological factors into the body, is a desirable technique to reconstruct the defective tissue. Embryonic stem cells, adult stem cells and induced pluripotent stem cells (iPSCs) offer the possibility of an unlimited source of cells to be differentiated into beta cells. Furthermore, there are numerous different materials available for scaffold manufacture including polyesters, naturally occurring proteins, extracellular matrix (ECM) and so on. Polylactic-co-glycolic acid (PLGA) is often used as the tissue engineering scaffold due to its good biocompatibility. In our study, fibroblasts and the extracellular matrix secreted by fibroblasts are used to effectively improve the biocompatibility of PLGA membrane and pancreatic stem cells, and promote the affinity between pancreatic stem cells and the PLGA membrane scaffold. The pancreatic stem cells grown on the fibroblastmodified PLGA membrane can be induced to differentiate into insulin secreting cells by the two-step induction method, and fibroblast-modified PLGA membrane plays a mechanical support role in the process of artificial islet tissue formation. The PLGA artificial islet tissue containing extracellular matrix of fibroblasts and insulin secreting cells can secrete insulin and reduce blood glucose within a short term in diabetic nude mice. Meanwhile, the Notch signaling system is closely related to the differentiation of pancreatic stem cells, our research also explores on the functional PLGA scaffold by altering the Notch ligands on fibroblast membrane, which would promote the differentiation of pancreatic stem cells.