The treatment of diabetes mellitus, as a chronic and complicated disease, is a valuable purpose. Islet transplantation can provide metabolic stability and insulin independence in type 1 diabetes patients. Diet and insulin therapy are only diabetes controllers and cannot remove all of the diabetes complications. Moreover, islet transplantation is more promising treatment than whole pancreas transplantation because of lesser invasive surgical procedure and morbidity and mortality. According to the importance of extracellular matrix for islet viability and function, microenvironment remodeling of pancreatic endocrine tissue can lead to more success in diabetes treatment by pancreatic islets. Production of bioengineered pancreas and remodeling of pancreas extracellular matrix provide essential microenvironment for re-vascularization, re-innervation and signaling cascades triggering. Therefore, islets show better viability and function in these conditions. Researchers conduct various scaffolds with different biomaterials for the improvement of islet viability, function and transplantation outcome. The attention to normal pancreas anatomy, embryology and histology is critical to understand the pancreatic Langerhans islets niche and finally to achieve efficient engineered structure. Therefore, in the present study, the status and components of the islets niche is mentioned and fundamental issues related to the tissue engineering of this structure is considered. The purpose of this review article is summarization of recent progress in the endocrine pancreas tissue engineering and biomaterials and biological aspects of it.
Biocompatible Materials ; Diabetes Complications ; Diabetes Mellitus ; Diet ; Embryology ; Extracellular Matrix ; Humans ; Insulin ; Islets of Langerhans ; Islets of Langerhans Transplantation ; Mortality ; Pancreas ; Pancreas Transplantation ; Tissue Engineering*

Pdx-1, an important transcription factor highlighting in the early pancreatic development, islet functions and pancreatic disorders, needs to be more investigated in zebrafish, and siRNA is still seldom applied in zebrafish embryo-related research. Our aim was to explore the role of pdx-1 in pancreatic development of zebrafish embryos by using siRNA approach. Microinjection, reverse transcriptase-PCR (RT-PCR), in situ hybridization and immunofluorescent staining were used in this research, and the morphology of the islet in normal zebrafish embryos, and in those treated with the siRNA specific to pdx-1 (siPDX-1) or siGFP was observed and compared. The expression of pdx-1 was detected in the stages of 1-cell, 2-cell, 4-cell, 8-cell, 16-cell, 16-hour by RT-PCT. The in situ hybridization and immunofluorescent staining results showed that siPDX-1 disturbed the formation of the islet in zebrafish embryos. Pdx-1 played multiple roles in maintaining the phenotype of the islet during embryogenesis in zebrafish.
Embryo, Nonmammalian ; Homeodomain Proteins/genetics ; Homeodomain Proteins/*metabolism ; Islets of Langerhans/cytology ; Islets of Langerhans/*embryology ; Islets of Langerhans/metabolism ; RNA Interference ; RNA, Small Interfering/*genetics ; Trans-Activators/genetics ; Trans-Activators/*metabolism ; Zebrafish

OBJECTIVETo explore the mechanisms of differentiation and development of pancreatic endocrine cells as well as pancreatic regeneration.

METHODSHuman embryonic pancreatic tissue at 7-14 weeks of gestation was collected. Diabetes mellitus rat model was induced with 65 mg/kg of streptozotocin. Insulin, glucagon, somatostatin, nestin, and cytokeratin 19 (CK19) of pancreatic tissues were observed by immunohistochemistry.

RESULTSAt 9 weeks of gestation, pancreatic epithelial cells began to co-express insulin, glucagon, somatostatin, and CK19 before migration. Islet cells gradually congregated along with the increase of aging, and at 14 weeks of gestation histological examination showed islet formation. At 12 weeks of gestation, nestin-positive cells could be seen in the pancreatic mesenchyme. During early embryogenesis, islet cells of pancreatic ducts co-expressed insulin, glucagon, and somatostatin. During pancreatic regeneration after damage, nestin expression of islet cells increased.

CONCLUSIONIn the early stage of embryogenesis, islet cells of primary pancreatic ducts can be differentiated to multipotential endocrine cells before migration. During tissue regeneration, pancreatic stem cells may differentiate and proliferate to form pancreatic islet.

Animals ; Cell Differentiation ; Diabetes Mellitus, Experimental ; chemically induced ; metabolism ; pathology ; Embryonic Development ; physiology ; Epithelial Cells ; cytology ; physiology ; Humans ; Insulin-Secreting Cells ; cytology ; physiology ; Islets of Langerhans ; cytology ; physiology ; Male ; Pancreas ; cytology ; embryology ; physiology ; Pancreatic Ducts ; cytology ; embryology ; physiology ; Rats ; Rats, Sprague-Dawley ; Regeneration ; physiology ; Stem Cells ; cytology ; metabolism ; physiology