期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2101258118
关键词
type 1 diabetes; convection; macroencapsulation; stem cell-derived beta cells
资金
- NIH [HL095722, U01DK104218]
- Juvenile Diabetes Research Foundation [3-SRA-2013-282]
- Incheon National University
Traditional islet transplantation for type 1 diabetes treatment has been hindered by lifelong immunosuppression, however, new convective nutrient transport technology shows potential to increase loading capacity, promote cell viability, and improve insulin secretion and fibrosis reduction for diabetic patients.
Islet transplantation for type 1 diabetes treatment has been limited by the need for lifelong immunosuppression regimens. This challenge has prompted the development of macroencapsulation devices (MEDs) to immunoprotect the transplanted islets. While promising, conventional MEDs are faced with insufficient transport of oxygen, glucose, and insulin because of the reliance on passive diffusion. Hence, these devices are constrained to two-dimensional, wafer-like geometries with limited loading capacity to maintain cells within a distance of passive diffusion. We hypothesized that convective nutrient transport could extend the loading capacity while also promoting cell viability, rapid glucose equilibration, and the physiological levels of insulin secretion. Here, we showed that convective transport improves nutrient delivery throughout the device and affords a threedimensional capsule geometry that encapsulates 9.7-fold-more cells than conventional MEDs. Transplantation of a convection-enhanced MED (ceMED) containing insulin-secreting beta cells into immunocompetent, hyperglycemic rats demonstrated a rapid, vascular-independent, and glucose-stimulated insulin response, resulting in early amelioration of hyperglycemia, improved glucose tolerance, and reduced fibrosis. Finally, to address potential translational barriers, we outlined future steps necessary to optimize the ceMED design for long-term efficacy and clinical utility.
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