Format

Send to

Choose Destination
JCI Insight. 2019 Nov 1;4(21). pii: 124644. doi: 10.1172/jci.insight.124644.

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

Author information

1
Gastroenterology Division, Department of Medicine.
2
Department of Cell and Developmental Biology, and.
3
Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
4
Genetic Resource Science, The Jackson Laboratory, Bar Harbor, Maine, USA.
5
Center for Cellular and Molecular Therapeutics, Department of Pathology and Laboratory Medicine.
6
Division of Endocrinology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
7
Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

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.

KEYWORDS:

Diabetes; Endocrinology; Islet cells

PMID:
31672937
DOI:
10.1172/jci.insight.124644
Free full text

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation
Loading ...
Support Center