Islet transplantation has now become a promising treatment for insulin-deficient diabetes mellitus.Compared to traditional diabetes treatments,cell therapy can restore endogenous insulin supplementation,but its large-...Islet transplantation has now become a promising treatment for insulin-deficient diabetes mellitus.Compared to traditional diabetes treatments,cell therapy can restore endogenous insulin supplementation,but its large-scale clinical application is impeded by donor shortages,immune rejection,and unsuitable transplantation sites.To overcome these challenges,an increasing number of studies have attempted to transplant hydrogel-encapsulated islet cells to treat diabetes.This review mainly focuses on the strategy of hydrogel-encapsulated pancreatic islet cells for diabetic cell therapy,including different cell sources encapsulated in hydrogels,encapsulation methods,hydrogel types,and a series of accessorial manners to improve transplantation outcomes.In addition,the formation and application challenges as well as prospects are also presented.展开更多
Islets transplantation is a promising treatment for type 1 diabetes mellitus. However, severe host immune rejection and poor oxygen/nutrients supply due to the lack of surrounding capillary network often lead to trans...Islets transplantation is a promising treatment for type 1 diabetes mellitus. However, severe host immune rejection and poor oxygen/nutrients supply due to the lack of surrounding capillary network often lead to transplantation failure. Herein, a novel bioartificial pancreas is constructed via islets microencapsulation in core-shell microgels and macroencapsulation in a hydrogel scaffold prevascularized in vivo. Specifically, a hydrogel scaffold containing methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and vascular endothelial growth factor (VEGF) is fabricated, which can delivery VEGF in a sustained style and thus induce subcutaneous angiogenesis. In addition, islets-laden core-shell microgels using methacrylated hyaluronic acid (HAMA) as microgel core and poly(ethylene glycol) diacrylate (PEGDA)/carboxybetaine methacrylate (CBMA) as shell layer are prepared, which provide a favorable microenvironment for islets and simultaneously the inhibition of host immune rejection via anti-adhesion of proteins and immunocytes. As a result of the synergistic effect between anti-adhesive core-shell microgels and prevascularized hydrogel scaffold, the bioartificial pancreas can reverse the blood glucose levels of diabetic mice from hyperglycemia to normoglycemia for at least 90 days. We believe this bioartificial pancreas and relevant fabrication method provide a new strategy to treat type 1 diabetes, and also has broad potential applications in other cell therapies.展开更多
基金supported by the National Natural Science Foundation Major International(Regional)Joint Research Program(grant number 82320108003)the National Natural Science Foundation of China(grant numbers 81970717 and 82170845)+2 种基金the National Key Research and Development Program of China(grant number 2021YFA1101800)the Key Research&Development Program of Jiangsu Province(grant number BE2022853)the Research Talent Cultivation Program of Zhongda Hospital Affiliated to Southeast University(grant number CZXM-GSP-RC28).
文摘Islet transplantation has now become a promising treatment for insulin-deficient diabetes mellitus.Compared to traditional diabetes treatments,cell therapy can restore endogenous insulin supplementation,but its large-scale clinical application is impeded by donor shortages,immune rejection,and unsuitable transplantation sites.To overcome these challenges,an increasing number of studies have attempted to transplant hydrogel-encapsulated islet cells to treat diabetes.This review mainly focuses on the strategy of hydrogel-encapsulated pancreatic islet cells for diabetic cell therapy,including different cell sources encapsulated in hydrogels,encapsulation methods,hydrogel types,and a series of accessorial manners to improve transplantation outcomes.In addition,the formation and application challenges as well as prospects are also presented.
基金sponsored by the National Natural Science Foundation of China(Grant Nos.51873071,32071321)the National Key Research and Development Program of China(2018YFC1106300).
文摘Islets transplantation is a promising treatment for type 1 diabetes mellitus. However, severe host immune rejection and poor oxygen/nutrients supply due to the lack of surrounding capillary network often lead to transplantation failure. Herein, a novel bioartificial pancreas is constructed via islets microencapsulation in core-shell microgels and macroencapsulation in a hydrogel scaffold prevascularized in vivo. Specifically, a hydrogel scaffold containing methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and vascular endothelial growth factor (VEGF) is fabricated, which can delivery VEGF in a sustained style and thus induce subcutaneous angiogenesis. In addition, islets-laden core-shell microgels using methacrylated hyaluronic acid (HAMA) as microgel core and poly(ethylene glycol) diacrylate (PEGDA)/carboxybetaine methacrylate (CBMA) as shell layer are prepared, which provide a favorable microenvironment for islets and simultaneously the inhibition of host immune rejection via anti-adhesion of proteins and immunocytes. As a result of the synergistic effect between anti-adhesive core-shell microgels and prevascularized hydrogel scaffold, the bioartificial pancreas can reverse the blood glucose levels of diabetic mice from hyperglycemia to normoglycemia for at least 90 days. We believe this bioartificial pancreas and relevant fabrication method provide a new strategy to treat type 1 diabetes, and also has broad potential applications in other cell therapies.
