Type 1 diabetes mellitus is an autoimmune disease,which results in the permanent destruction of β-cells of the pancreatic islets of Langerhans.While exogenous insulin therapy has dramatically improved the quality of ...Type 1 diabetes mellitus is an autoimmune disease,which results in the permanent destruction of β-cells of the pancreatic islets of Langerhans.While exogenous insulin therapy has dramatically improved the quality of life,chronic diabetic complications develop in a substantial proportion of subjects and these complications generally progress and worsen over time.Although intensive insulin therapy has proven effective to delay and sometimes prevent the progression of complications such as nephropathy,neuropathy or retinopathy,it is difficult to achieve and maintain long term in most subjects.Reasons for this diff iculty include compliance issues and the increased risk of severe hypoglycemic episodes,which are generally associated with intensification of exogenous insulin therapy.Clinical studies have shown that transplantation of pancreas or purified pancreatic islets can support glucose homeostasis in type 1 diabetic patients.Islet transplantation carries the special advantages of being less invasive and resulting in fewer complications compared with the traditional pancreas or pancreas-kidney transplantation.However,islet transplantation efforts have limitations including the short supply of donor pancreata,the paucity of experienced islet isolation teams,side effects of immunosuppressants and poor long-term results.The purpose of this article is to review recent progress in clinical islet transplantation for the treatment of diabetes.展开更多
通过对68例2型糖尿病患者进行精氨酸刺激试验(AST)和胰高血糖素刺激试验(GST),比较其对胰岛β细胞功能的评价,发现精氨酸刺激后C肽于3min达高峰,此峰值与胰高血糖素刺激后6minC肽差异无统计学意义,而且以精氨酸刺激试验3 min C肽是否大...通过对68例2型糖尿病患者进行精氨酸刺激试验(AST)和胰高血糖素刺激试验(GST),比较其对胰岛β细胞功能的评价,发现精氨酸刺激后C肽于3min达高峰,此峰值与胰高血糖素刺激后6minC肽差异无统计学意义,而且以精氨酸刺激试验3 min C肽是否大于0.6 nmol/L作为选择治疗方案的参考(与GST结果接近),与临床符合情况较好。展开更多
Objective To explore the mechanisms of differentiation and development of pancreatic endocrine cells as well as pancreatic regeneration.Methods Human embryonic pancreatic tissue at 7-14 weeks of gestation was collecte...Objective To explore the mechanisms of differentiation and development of pancreatic endocrine cells as well as pancreatic regeneration.Methods Human 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.Results At 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.Conclusion In 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.展开更多
Currently, there does not exist a strategy that can reduce diabetes and scientists are working towards a cure and innovative approaches by employing stem cellbased therapies. On the other hand, bioprinting technology ...Currently, there does not exist a strategy that can reduce diabetes and scientists are working towards a cure and innovative approaches by employing stem cellbased therapies. On the other hand, bioprinting technology is a novel therapeutic approach that aims to replace the diseased or lost β-cells, insulin-secreting cells in the pancreas, which can potentially regenerate damaged organs such as the pancreas. Stem cells have the ability to differentiate into various cell lines including insulinproducing cells. However, there are still barriers that hamper the successful differentiation of stem cells into β-cells. In this review, we focus on the potential applications of stem cell research and bioprinting that may be targeted towards replacing the β-cells in the pancreas and may offer approaches towards treatment of diabetes. This review emphasizes on the applicability of employing both stem cells and other cells in 3 D bioprinting to generate substitutes for diseased β-cells and recover lost pancreatic functions. The article then proceeds to discuss the overall research done in the field of stem cell-based bioprinting and provides future directions for improving the same for potential applications in diabetic research.展开更多
基金Supported by The All Saints Health Foundation (in part)
文摘Type 1 diabetes mellitus is an autoimmune disease,which results in the permanent destruction of β-cells of the pancreatic islets of Langerhans.While exogenous insulin therapy has dramatically improved the quality of life,chronic diabetic complications develop in a substantial proportion of subjects and these complications generally progress and worsen over time.Although intensive insulin therapy has proven effective to delay and sometimes prevent the progression of complications such as nephropathy,neuropathy or retinopathy,it is difficult to achieve and maintain long term in most subjects.Reasons for this diff iculty include compliance issues and the increased risk of severe hypoglycemic episodes,which are generally associated with intensification of exogenous insulin therapy.Clinical studies have shown that transplantation of pancreas or purified pancreatic islets can support glucose homeostasis in type 1 diabetic patients.Islet transplantation carries the special advantages of being less invasive and resulting in fewer complications compared with the traditional pancreas or pancreas-kidney transplantation.However,islet transplantation efforts have limitations including the short supply of donor pancreata,the paucity of experienced islet isolation teams,side effects of immunosuppressants and poor long-term results.The purpose of this article is to review recent progress in clinical islet transplantation for the treatment of diabetes.
文摘通过对68例2型糖尿病患者进行精氨酸刺激试验(AST)和胰高血糖素刺激试验(GST),比较其对胰岛β细胞功能的评价,发现精氨酸刺激后C肽于3min达高峰,此峰值与胰高血糖素刺激后6minC肽差异无统计学意义,而且以精氨酸刺激试验3 min C肽是否大于0.6 nmol/L作为选择治疗方案的参考(与GST结果接近),与临床符合情况较好。
文摘Objective To explore the mechanisms of differentiation and development of pancreatic endocrine cells as well as pancreatic regeneration.Methods Human 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.Results At 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.Conclusion In 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.
基金Supported by the National Institutes of Health,No.NIH BUILD Pilot 8UL1GM118970-02,NIH 1SC2HL134642-01the National Science Foundation,NSFPREM program,No.DMR:1205302the PREM Center for Energy and Biomaterials,No.DMR:1827745
文摘Currently, there does not exist a strategy that can reduce diabetes and scientists are working towards a cure and innovative approaches by employing stem cellbased therapies. On the other hand, bioprinting technology is a novel therapeutic approach that aims to replace the diseased or lost β-cells, insulin-secreting cells in the pancreas, which can potentially regenerate damaged organs such as the pancreas. Stem cells have the ability to differentiate into various cell lines including insulinproducing cells. However, there are still barriers that hamper the successful differentiation of stem cells into β-cells. In this review, we focus on the potential applications of stem cell research and bioprinting that may be targeted towards replacing the β-cells in the pancreas and may offer approaches towards treatment of diabetes. This review emphasizes on the applicability of employing both stem cells and other cells in 3 D bioprinting to generate substitutes for diseased β-cells and recover lost pancreatic functions. The article then proceeds to discuss the overall research done in the field of stem cell-based bioprinting and provides future directions for improving the same for potential applications in diabetic research.