Type 1 diabetes is caused by insulin deficiency due to the loss of beta cells in the islets of Langerhans.In severe cases,islet transplantation into the portal vein is performed.However,due to the loss of transplanted...Type 1 diabetes is caused by insulin deficiency due to the loss of beta cells in the islets of Langerhans.In severe cases,islet transplantation into the portal vein is performed.However,due to the loss of transplanted islets and the failure of islet function,the 5-year insulin independence rate of these patients is<50%.In this study,we developed a long-term,insulin-secreting,3 Dbioprinted construct implanted subcutaneously with the aim of preventing islet loss.The bioprinted construct was fabricated by the multi-layer bioprinting of beta-cell(mouse insulinoma-6:MIN-6)-encapsulated alginate bioink and poly(caprolactone)biodegradable polymer.A glucose response assay revealed that the bioprinted constructs proliferated and released insulin normally during the 4-week in vitro period.Bioprinted MIN-6 generated clusters with a diameter of 100-200μm,similar to the original pancreatic islets in the construct.In an in vivo study using type 1 diabetes mice,animals implanted with bioprinted constructs showed three times higher insulin secretion and controlled glucose levels at 8 weeks after implantation.Because the implanted,bioprinted constructs had a positive effect on insulin secretion in the experimental animals,the survival rate of the implanted group(75%)was three times higher than that of the non-implanted group(25%).The results suggest that the proposed,3 D-bioprinted,subcutaneous construct can be a better alternative to portal vein islet transplantation.展开更多
基金supported by the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(No.HH21C0011)Gachon University Gil Medical Center(No.FRD 2021-02)。
文摘Type 1 diabetes is caused by insulin deficiency due to the loss of beta cells in the islets of Langerhans.In severe cases,islet transplantation into the portal vein is performed.However,due to the loss of transplanted islets and the failure of islet function,the 5-year insulin independence rate of these patients is<50%.In this study,we developed a long-term,insulin-secreting,3 Dbioprinted construct implanted subcutaneously with the aim of preventing islet loss.The bioprinted construct was fabricated by the multi-layer bioprinting of beta-cell(mouse insulinoma-6:MIN-6)-encapsulated alginate bioink and poly(caprolactone)biodegradable polymer.A glucose response assay revealed that the bioprinted constructs proliferated and released insulin normally during the 4-week in vitro period.Bioprinted MIN-6 generated clusters with a diameter of 100-200μm,similar to the original pancreatic islets in the construct.In an in vivo study using type 1 diabetes mice,animals implanted with bioprinted constructs showed three times higher insulin secretion and controlled glucose levels at 8 weeks after implantation.Because the implanted,bioprinted constructs had a positive effect on insulin secretion in the experimental animals,the survival rate of the implanted group(75%)was three times higher than that of the non-implanted group(25%).The results suggest that the proposed,3 D-bioprinted,subcutaneous construct can be a better alternative to portal vein islet transplantation.
