Improvement of human islet cryopreservation by a p38 MAPK inhibitor

Am J Transplant. 2007 May;7(5):1224-32. doi: 10.1111/j.1600-6143.2007.01741.x. Epub 2007 Feb 27.


The activation of p38 mitogen-activated protein kinase (MAPK) has been shown to cause ischemia/reperfusion injury of several organs used for transplantation and also to play a significant role in primary islet graft nonfunction. Activation of p38 MAPK may also occur during islet cryopreservation and thawing. In this study, a p38 MAPK inhibitor (p38IH) was applied to human islet cryopreservation to improve islet yield and quality after thawing. Under serum-free conditions, human islets were cryopreserved, thawed and cultured using our standard procedures. Three types of solutions were tested: conventional RPMI1640 medium (RPMI), a newly developed islet cryopreservation solution (ICS), and ICS supplemented with a p38IH, SD-282 (ICS-p38IH). Activation or inhibition of p38 MAPK was demonstrated by the diminished phosphorylation of HSP27 substrate. Islet recovery on day 2 after thawing was highest with ICS-p38IH and islet viability was not significantly different in the three groups. beta Cell numbers and function were the highest in islets cryopreserved with ICS-p38IH. Glucose-stimulated human C-peptide levels were 86% of that of the nonfrozen islets when measured 4 weeks after transplantation into NODscid mice. This improvement may provide an opportunity to establish islet banks and allow the use of cryopreserved islets for clinical transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Peptide / metabolism
  • Cell Count
  • Cell Survival
  • Cells, Cultured
  • Cryopreservation / methods*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / surgery
  • Enzyme Inhibitors / pharmacology*
  • Glucose / pharmacology
  • Humans
  • Indoles / pharmacology*
  • Insulin / metabolism
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans Transplantation / methods
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Organ Preservation / methods*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • C-Peptide
  • Enzyme Inhibitors
  • Indoles
  • Insulin
  • indole-5-carboxamide
  • p38 Mitogen-Activated Protein Kinases
  • Glucose