A therapeutic convection-enhanced macroencapsulation device for enhancing beta cell viability and insulin secretion
UMass Chan AffiliationsProgram in Molecular Medicine, Diabetes Center of Excellence
Document TypeJournal Article
stem cell–derived β cells
type 1 diabetes
Endocrine System Diseases
Endocrinology, Diabetes, and Metabolism
Hormones, Hormone Substitutes, and Hormone Antagonists
MetadataShow full item record
AbstractIslet 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 three-dimensional 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.
Yang K, O'Cearbhaill ED, Liu SS, Zhou A, Chitnis GD, Hamilos AE, Xu J, Verma MKS, Giraldo JA, Kudo Y, Lee EA, Lee Y, Pop R, Langer R, Melton DA, Greiner DL, Karp JM. A therapeutic convection-enhanced macroencapsulation device for enhancing β cell viability and insulin secretion. Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):e2101258118. doi: 10.1073/pnas.2101258118. PMID: 34504013; PMCID: PMC8449352. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/42732
Full author list omitted for brevity. For the full list of authors, see article.
RightsCopyright © 2021 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Except where otherwise noted, this item's license is described as Copyright © 2021 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).