Effect of an oxygen-generating scaffold on the viability and insulin secretion function of porcine neonatal pancreatic cell clusters

Xenotransplantation. 2018 Mar;25(2):e12378. doi: 10.1111/xen.12378. Epub 2018 Jan 10.

Abstract

Background: Islet encapsulation techniques have shown limited success in maintaining islet survival and function because encapsulation decreases oxygen supply. In this study, an oxygen-generating scaffold was fabricated to prevent hypoxic cell damage and improve the viability and insulin secretion of islets.

Methods: We fabricated an oxygen-generating scaffold by mixing calcium peroxide (CaO2 ) with polydimethylsiloxane (PDMS). We evaluated the effects of the oxygen-generating PDMS + CaO2 scaffold on viability, caspase-3 and caspase-7 activity, oxygen consumption rate (OCR), glucose-stimulated insulin secretion (GSIS), hypoxic cell marker expression, and reactive oxygen species (ROS) levels in porcine neonatal pancreatic cell clusters (NPCCs). We also fabricated a microfluidic device that allowed measuring the effects of the oxygen-generating scaffold on viability.

Results: Oxygen generation by the PDMS + CaO2 scaffold was sustained for more than 24 hours in vitro. NPCCs encapsulated in PDMS + CaO2 showed higher viability than NPCCs in PDMS scaffolds and control NPCCs grown without a scaffold. PDMS + CaO2 -encapsulated NPCCs showed lower caspase-3 and caspase-7 activity, hypoxic cell expression, and ROS levels, and higher OCR and GSIS than those in PDMS or control cells. Using the microfluidic device, we observed that the viability of PDMS + CaO2 -encapsulated NPCCs was higher than that of PDMS-encapsulated NPCCs.

Conclusions: NPCCs in PDMS + CaO2 scaffolds show higher viability and insulin secretion than do NPCCs in PDMS scaffolds and control cells. Therefore, this oxygen-generating scaffold has potential for application in future islet transplantation studies.

Keywords: insulin secretion; macro-encapsulation; microfluidic system; neonatal pancreatic cell clusters; oxygen-generating scaffold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blood Glucose / metabolism
  • Cell Survival / physiology*
  • Diabetes Mellitus, Experimental
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans Transplantation* / methods
  • Oxygen / metabolism*
  • Pancreas / metabolism
  • Swine
  • Transplantation, Heterologous / methods

Substances

  • Blood Glucose
  • Insulin
  • Oxygen