Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum

Jacqueline A. Burke, Yunxiao Zhu, Xiaomin Zhang, Peter D. Rios, Ira Joshi, Daisy Lopez, Hafsa Nasir, Sharon Roberts, Quetzalli Rodriguez, James McGarrigle, David Cook, Jose Oberholzer, Xunrong Luo, Guillermo A. Ameer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Clinical outcomes for total-pancreatectomy followed by intraportal islet autotransplantation (TP-IAT) to treat chronic pancreatitis (CP) are suboptimal due to pancreas inflammation, oxidative stress during islet isolation, and harsh engraftment conditions in the liver’s vasculature. We describe a thermoresponsive, antioxidant macromolecule poly(polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) to protect islet redox status and function and to enable extrahepatic omentum islet engraftment. PPCN solution transitions from a liquid to a hydrogel at body temperature. Islets entrapped in PPCN and exposed to oxidative stress remain functional and support long-term euglycemia, in contrast to islets entrapped in a plasma-thrombin biologic scaffold. In the nonhuman primate (NHP) omentum, PPCN is well-tolerated and mostly resorbed without fibrosis at 3 months after implantation. In NHPs, autologous omentum islet transplantation using PPCN restores normoglycemia with minimal exogenous insulin requirements for >100 days. This preclinical study supports TP-IAT with PPCN in patients with CP and highlights antioxidant properties as a mechanism for islet function preservation.

Original languageEnglish (US)
Article numbereadk3081
JournalScience Advances
Volume10
Issue number23
DOIs
StatePublished - Jun 7 2024

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum'. Together they form a unique fingerprint.

Cite this