Pankreatik adacık engrafmanını iyileştirmek için biyomimetik hücre dışı ortam dizayn edilmesi

Pancreatic islet transplantation has emerged as a promising treatment for type 1 diabetes (T1D) and engraftment of beta cells after transplantation determines the success of clinical setting. However, clinical application of islet transplantation is still limited by life-long use of immunosuppressive drugs and insufficient number of islets to achieve normoglycemia. In this study, we tailored biochemical and biophysical properties of hydrogels to promote insulin secretion function and immunoregulatory potential through incorporation of mesenchymal stem cells (MSCs) and natural extracellular matrix mimetic peptides such as RGDS, IKVAV and insulinotropic peptide (GLP-1). Co-encapsulation of islets with MSCs and/or peptides contributed to significant increases in insulin secretion compared to control. Although deleterious effects of cytokines were not completely inhibited, we observed that protection against pro-inflammatory cytokines can be achieved in free and PEG hydrogel encapsulated MIN6-MSC heterospheroids. To tailor biophysical properties of islet microenvironment, we developed unique type of nano-thin coating for insulin secreting beta cell aggregates. These aggregates which were prepared as pseudoislets through hanging drop method were coated with sequential layers of nanogels using physiologically compatible medium without toxic prepolymer solutions. These coated pseudoislets were determined as viable and functional for insulin secretion. We also confirmed in vivo biocompatibility of CHPOA nanogels through subcutaneous transplantation into CD1 mouse. This study is promising and offers new opportunities through coating of insulin secreting islets with advanced functional materials under completely physiological conditions and will contribute to longer functional islets for clinical translation of cell transplantation technology and particularly for the treatment of T1D.