Improvement of short-term hypothermic preservation of microencapsulated hepatocytes

Biotechnol Lett. 2016 Jun;38(6):909-17. doi: 10.1007/s10529-016-2063-x. Epub 2016 Mar 4.

Abstract

Objectives: To determine the optimal storage solution containing suitable protective agents for the preservation of microencapsulated hepatocytes at 4 °C as well as the optimum incubation time after hypothermic preservation.

Results: L15 was the optimum solution for both maintaining microcapsule integrity and cell viability. Furthermore, 5 %(v/v) PEG (20 or 35 kDa) added to Leibovitz-15 medium was optimal for microencapsulated C3A cells, enhancing cell viability and liver-specific functions, including albumin and urea synthesis as well as CYP1A2 and CYP3A4 activities. The transcription levels of several CYP450-related genes were also dramatically increased in cells incubated in the optimal solution. Pre-incubation for 2 h was the optimal time for restoring favorable levels of CYP1A2 and CYP3A4 activities in microencapsulated C3A cells for short term, 2 day storage.

Conclusions: Leibovitz-15 medium supplemented with 5 % (v/v) PEG is a promising cold solution for microencapsulated hepatocytes at 4 °C, with an incubation of 2 h at 37 °C after hypothermic preservation being the best incubation duration for further cell application.

Keywords: Cell function; Cell viability; Hepatocytes; Hypothermic preservation; Microcapsule integrity; Microencapsulated hepatocytes.

MeSH terms

  • Cell Survival
  • Cryopreservation / methods*
  • Cryoprotective Agents / pharmacology
  • Culture Media* / chemistry
  • Culture Media* / pharmacology
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP3A
  • Drug Compounding
  • Gene Expression Regulation
  • Hepatocytes / drug effects
  • Hepatocytes / physiology*
  • Humans
  • Polyethylene Glycols / pharmacology

Substances

  • Cryoprotective Agents
  • Culture Media
  • Polyethylene Glycols
  • CYP1A2 protein, human
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human