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

Autor: Burke JA; Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.; Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL 60208, USA., Zhu Y; Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.; Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL 60208, USA., Zhang X; Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL 60208, USA.; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Rios PD; CellTrans Inc., Chicago, IL 60612, USA., Joshi I; CellTrans Inc., Chicago, IL 60612, USA., Lopez D; CellTrans Inc., Chicago, IL 60612, USA., Nasir H; CellTrans Inc., Chicago, IL 60612, USA., Roberts S; CellTrans Inc., Chicago, IL 60612, USA., Rodriguez Q; CellTrans Inc., Chicago, IL 60612, USA., McGarrigle J; CellTrans Inc., Chicago, IL 60612, USA., Cook D; CellTrans Inc., Chicago, IL 60612, USA., Oberholzer J; CellTrans Inc., Chicago, IL 60612, USA., Luo X; Duke Transplant Center, Duke University School of Medicine, Durham, NC 27710, USA., Ameer GA; Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.; Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL 60208, USA.; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.; Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208 USA.; Simpson Querrey Institute, Northwestern University, Chicago, IL 60611, USA.; International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Jun 07; Vol. 10 (23), pp. eadk3081. Date of Electronic Publication: 2024 Jun 07.
DOI: 10.1126/sciadv.adk3081
Abstrakt: 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.
Databáze: MEDLINE
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