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iPreP is a three-dimensional nanofibrillar cellulose hydrogel platform for long-term ex vivo preservation of human islets
Yi-Ju Chen, … , Paul Gadue, Ben Z. Stanger
Yi-Ju Chen, … , Paul Gadue, Ben Z. Stanger
Published November 1, 2019
Citation Information: JCI Insight. 2019;4(21):e124644. https://doi.org/10.1172/jci.insight.124644.
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Resource and Technical Advance Endocrinology

iPreP is a three-dimensional nanofibrillar cellulose hydrogel platform for long-term ex vivo preservation of human islets

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Abstract

Islet transplantation is an effective therapy for achieving and maintaining normoglycemia in patients with type 1 diabetes mellitus. However, the supply of transplantable human islets is limited. Upon removal from the pancreas, islets rapidly disintegrate and lose function, resulting in a short interval for studies of islet biology and pretransplantation assessment. Here, we developed a biomimetic platform that can sustain human islet physiology for a prolonged period ex vivo. Our approach involved the creation of a multichannel perifusion system to monitor dynamic insulin secretion and intracellular calcium flux simultaneously, enabling the systematic evaluation of glucose-stimulated insulin secretion under multiple conditions. Using this tool, we developed a nanofibrillar cellulose hydrogel–based islet-preserving platform (iPreP) that can preserve islet viability, morphology, and function for nearly 12 weeks ex vivo, and with the ability to ameliorate glucose levels upon transplantation into diabetic hosts. Our platform has potential applications in the prolonged maintenance of human islets, providing an expanded time window for pretransplantation assessment and islet studies.

Authors

Yi-Ju Chen, Taiji Yamazoe, Karla F. Leavens, Fabian L. Cardenas-Diaz, Andrei Georgescu, Dongeun Huh, Paul Gadue, Ben Z. Stanger

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Figure 4

In vivo functional assessment of human islets following long-term 3D NFC hydrogel culture.

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In vivo functional assessment of human islets following long-term 3D NFC...
(A) Blood glucose levels in diabetic mice after transplantation of human islets cultured ex vivo for 31 days. Transwell- or hydrogel-cultured human islets from the same donor (200 islets per mouse, counted on day 0) were retrieved on day 31 and transplanted under the kidney capsule of STZ-induced diabetic NOD/SCID mice. Three mice were transplanted with Transwell cultured islets, and 2 mice were transplanted with hydrogel-cultured islets. Values are shown as mean ± SEM. Yellow indicates hyperglycemia; green, normoglycemia. Two-tailed t test; *P < 0.05, **P < 0.01. (B) Human C-peptide levels in diabetic mice after transplantation. Hydrogel-cultured human islets from the same donor (400 islets per mouse, counted on day 0) were retrieved on day 31 and transplanted into 2 STZ-induced diabetic NOD/SCID mice. Blood samples were collected from mouse tail vein at the indicated time points after transplantation, and human C-peptide levels were measured from serum. Data are shown as mean ± SEM.

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