Bckground Stem cells, which have the ability to differentiate into insulin-producing cells （IPCs）, would provide a potentially unlimited source of islet cells for transplantation and alleviate the major limitations ...Bckground Stem cells, which have the ability to differentiate into insulin-producing cells （IPCs）, would provide a potentially unlimited source of islet cells for transplantation and alleviate the major limitations of availability and allogeneic rejection. Therefore, the utilization of stem cells is becoming the most promising therapy for diabetes mellitus （DM）. Here, we studied the differentiation capacity of the diabetic patient＇s bone marrow-derived mesenchymal stem cells （MSCs） and tested the feasibility of using MSCs for β-cell replacement. Methods Bone marrow-derived MSCs were obtained from 10 DM patients （5 type 1 DM and 5 type 2 DM） and induced to IPCs under a three-stage protocol. Representative cell surface antigen expression profiles of MSCs were analysed by flow cytometric analysis. Reverse transcription-polymerase chain reaction （RT-PCR） was performed to detect multiple genes related to pancreatic β-cell development and function. The identity of the IPCs was illustrated by the analysis of morphology, ditizone staining and immunocytochemistry. Release of insulin by these cells was confirmed by immunoradioassay. Results Flow cytometric analysis of MSCs at passage 3 showed that these cells expressed high levels of CD29 （98.28%）, CD44 （99.56%） and CD106 （98.34%）. Typical islet-like cell clusters were observed at the end of the protocol （18 days）. Ditizone staining and immunohistochemistry for insulin were both positive. These differentiated cells at stage 2 （10 days） expressed nestin, pancreatic duodenal homeobox-1 （PDX-1）, Neurogenin3, Pax4, insulin, glucagon, but at stage 3 （18 days） we observed the high expression of PDX-1, insulin, glucagon. Insulin was secreted by these cells in response to different concentrations of glucose stimulation in a regulated manner （P〈0.05）. Conclusions Bone marrow-derived MSCs from DM patients can differentiate into functional IPCs under certain conditions in vitro. Using diabetic patient＇s own bone marrow-derived MSCs as a source of autologous IPCs for β-cell reDlacement would be feasible.展开更多
Background Diabetes mellitus has become epidemic in recent years in China. We investigated the prevalence of hyperglycaemia and inadequate glycaemic control among type 2 diabetic inpatients from ten university teachin...Background Diabetes mellitus has become epidemic in recent years in China. We investigated the prevalence of hyperglycaemia and inadequate glycaemic control among type 2 diabetic inpatients from ten university teaching hospitals in Guangdong Province, China. Methods Inadequate glycaemic control in diabetic patients was defined as HbA1c 〉 6.5%. Therapeutic regimens included no-intervention, lifestyle only, oral antiglycemic agents （OA）, insulin plus OA （insulin＋OA）, or insulin only. Antidiabetic managements included monotherapy, double therapy, triple or quadruple therapy. Results Among 493 diabetic inpatients with known history, 75% had HbA1c ≥ 6.5%. inadequate glucose control rates were more frequently seen in patients on insulin＋OA regimen （97%） ,than on OA regimen （71%） （P 〈0.001）, and more frequent in patients on combination therapy （81%-96%） than monotherapy （7,5%） （P 〈0.0,5）. Patients on insulin differed significantly from patients on OA by mean HbA1c, glycemic control rate, diabetes duration, microvascular complications, and BMI （P 〈0.01）. Conclusions This study showed that glycaemic control of type 2 diabetic patients deteriorated for patients who received insulin and initiation time of insulin was usually delayed, it is up to clinicians to move from the traditional stepwise therapy to a more active and early combination antidiabetic therapy to provide better glucose control.展开更多
文摘Bckground Stem cells, which have the ability to differentiate into insulin-producing cells （IPCs）, would provide a potentially unlimited source of islet cells for transplantation and alleviate the major limitations of availability and allogeneic rejection. Therefore, the utilization of stem cells is becoming the most promising therapy for diabetes mellitus （DM）. Here, we studied the differentiation capacity of the diabetic patient＇s bone marrow-derived mesenchymal stem cells （MSCs） and tested the feasibility of using MSCs for β-cell replacement. Methods Bone marrow-derived MSCs were obtained from 10 DM patients （5 type 1 DM and 5 type 2 DM） and induced to IPCs under a three-stage protocol. Representative cell surface antigen expression profiles of MSCs were analysed by flow cytometric analysis. Reverse transcription-polymerase chain reaction （RT-PCR） was performed to detect multiple genes related to pancreatic β-cell development and function. The identity of the IPCs was illustrated by the analysis of morphology, ditizone staining and immunocytochemistry. Release of insulin by these cells was confirmed by immunoradioassay. Results Flow cytometric analysis of MSCs at passage 3 showed that these cells expressed high levels of CD29 （98.28%）, CD44 （99.56%） and CD106 （98.34%）. Typical islet-like cell clusters were observed at the end of the protocol （18 days）. Ditizone staining and immunohistochemistry for insulin were both positive. These differentiated cells at stage 2 （10 days） expressed nestin, pancreatic duodenal homeobox-1 （PDX-1）, Neurogenin3, Pax4, insulin, glucagon, but at stage 3 （18 days） we observed the high expression of PDX-1, insulin, glucagon. Insulin was secreted by these cells in response to different concentrations of glucose stimulation in a regulated manner （P〈0.05）. Conclusions Bone marrow-derived MSCs from DM patients can differentiate into functional IPCs under certain conditions in vitro. Using diabetic patient＇s own bone marrow-derived MSCs as a source of autologous IPCs for β-cell reDlacement would be feasible.
文摘Background Diabetes mellitus has become epidemic in recent years in China. We investigated the prevalence of hyperglycaemia and inadequate glycaemic control among type 2 diabetic inpatients from ten university teaching hospitals in Guangdong Province, China. Methods Inadequate glycaemic control in diabetic patients was defined as HbA1c 〉 6.5%. Therapeutic regimens included no-intervention, lifestyle only, oral antiglycemic agents （OA）, insulin plus OA （insulin＋OA）, or insulin only. Antidiabetic managements included monotherapy, double therapy, triple or quadruple therapy. Results Among 493 diabetic inpatients with known history, 75% had HbA1c ≥ 6.5%. inadequate glucose control rates were more frequently seen in patients on insulin＋OA regimen （97%） ,than on OA regimen （71%） （P 〈0.001）, and more frequent in patients on combination therapy （81%-96%） than monotherapy （7,5%） （P 〈0.0,5）. Patients on insulin differed significantly from patients on OA by mean HbA1c, glycemic control rate, diabetes duration, microvascular complications, and BMI （P 〈0.01）. Conclusions This study showed that glycaemic control of type 2 diabetic patients deteriorated for patients who received insulin and initiation time of insulin was usually delayed, it is up to clinicians to move from the traditional stepwise therapy to a more active and early combination antidiabetic therapy to provide better glucose control.
