Improvement of islet function and survival by integration of perfluorodecalin into microcapsules in vivo and in vitro

Abstract

Hypoxic injury of islets is a major obstacle for encapsulated islet transplantation into the peritoneal cavity. To improve oxygen delivery to encapsulated islets, we integrated 20% of the oxygen carrier material, perfluorodecalin (PFD), in alginate capsules mixed with islets (PFD-alginate). Integration of PFD clearly improved islet viability and decreased reactive oxygen species production compared to islets encapsulated with alginate only (alginate) and naked islets exposed to hypoxia in vitro. In PFD-alginate capsules, HIF-1α expression was minimal, and insulin expression was well maintained. Furthermore, the best islet function represented by glucose-stimulated insulin secretion was observed for the PFD-alginate capsules in hypoxic condition. For the in vivo study, the same number of naked islets and encapsulated islets (alginate and PFD-alginate) was transplanted into streptozotocin-induced diabetic mice. Nonfasting blood glucose levels and the area under the curve for glucose based on intraperitoneal glucose tolerance tests in the PFD-alginate group were lower than in the alginate group. The harvested islets stained positive for insulin in all groups, but the ratio of dead cell area was 4 times higher in the alginate group than in the PFD-alginate group. In conclusion, integration of PFD in alginate microcapsules improved islet function and survival by minimizing the hypoxic damage of islets after intraperitoneal transplantation.

Bilirubin Improves the Quality and Function of Hypothermic Preserved Islets by Its Antioxidative and Anti-inflammatory Effect

“…The mice transplanted with islets without bilirubin protection showed a large fluctuation of blood glucose within 5 days, which could be explained by the hypoxia and initial stage inflammation impaired islets. 31 On the contrary, islets treated with bilirubin suffered from less hypoxia-induced damage and could recover better in shorter time, leading to the stabilization of blood glucose in the transplanted mice within 5 days. It is worth mention that abdominal bilirubin injection (2 mg/kg) did not affect the blood glucose levels, but these mice all died after 10 days.…”

Perftoran® Inhibits Hypoxia-Associated Resistance in Lung Cancer Cells to Carboplatin

“…Cells were seeded in complete RPMI-1640 medium (10% (v/v) fetal bovine serum, 2 mM l-glutamine, and 1% (v/v) 1002 U/ml penicillin/streptomycin). All cell experiments were performed under “hypoxic conditions” (1% O 2 , 5% CO 2 , 85% N 2 , and 37°C) and compared with the control “normoxic conditions” (20% O 2 , 5% CO 2 , 75% N 2 , and 37°C) ( Lee et al, 2018 ). Unless otherwise noted, chemicals and supplements were purchased from Sigma/Aldrich, VA, United States.…”

Design Considerations for Macroencapsulation Devices for Stem Cell Derived Islets for the Treatment of Type 1 Diabetes

“…[ 134 , 135 ] Owing to their unique characteristics, PFCs have been used in different applications, including organ preservation, [ 136 , 137 ] artificial blood substitutes, [ 138 ] or oxygen delivery to cells. PFC‐based oxygenated scaffolds (perfluorodecalin (PFD) emulsions, [ 139 ] PFD‐alginate capsules [ 140 ] ) reduced hypoxia and cell death (reducing ROS generation) in encapsulated stem cells, [ 141 ] β ‐cells, [ 139 ] and pancreatic islets, both in culture [ 139 , 142 , 143 ] and implanted in mice. [ 140 ] PFCs can be pre‐loaded with oxygen prior cell encapsulation, proving an additional initial oxygen supply.…”

“…PFC‐based oxygenated scaffolds (perfluorodecalin (PFD) emulsions, [ 139 ] PFD‐alginate capsules [ 140 ] ) reduced hypoxia and cell death (reducing ROS generation) in encapsulated stem cells, [ 141 ] β ‐cells, [ 139 ] and pancreatic islets, both in culture [ 139 , 142 , 143 ] and implanted in mice. [ 140 ] PFCs can be pre‐loaded with oxygen prior cell encapsulation, proving an additional initial oxygen supply. Additionally, once the initial oxygen payload has been delivered, the remaining PFCs could effectively increase the oxygen permeability inside the macroencapsulation device, improving cell nutrition.…”