title: Inhibition of p38 mitogen-activated protein kinase protects human islets from cryoinjury and improves the yield, viability, and quality of frozen-thawed islets.
abstract: The development of an optimal islet cryopreservation method will permit transplantation of islets from multiple donors in a single procedure and contribute to alleviation of the islet shortage. In this study, we have improved human islet cryopreservation methods under serum-free conditions using an intracellular-based islet cryopreservation solution (ICS), especially supplemented with a p38 pathway inhibitor (p38IH) to suppress p38 mitogen-activated protein kinase (MAPK) activation. Three different solutions were compared for freezing and thawing of human islets (1) conventional RPMI1640 medium, (2) ICS, and (3) ICS supplemented with a p38IH, SD-282 (ICS-p38IH). Islet cryopreservation with ICS-p38IH significantly improved islet recovery, viability, and quality after thawing of cryopreserved islets. This improvement may allow the use of cryopreserved islets in clinical islet transplantation.
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center/Beckman Research Institute, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: K
authors.initials: K
authors.lastname: Omori
authors.forename: L
authors.initials: L
authors.lastname: Valiente
authors.forename: C
authors.initials: C
authors.lastname: Orr
authors.forename: J
authors.initials: J
authors.lastname: Rawson
authors.forename: K
authors.initials: K
authors.lastname: Ferreri
authors.forename: I
authors.initials: I
authors.lastname: Todorov
authors.forename: S
authors.initials: S
authors.lastname: Medicherla
authors.forename: A A
authors.initials: AA
authors.lastname: Protter
authors.forename: G F
authors.initials: GF
authors.lastname: Schreiner
authors.forename: A D
authors.initials: AD
authors.lastname: Riggs
authors.forename: F
authors.initials: F
authors.lastname: Kandeel
authors.forename: Y
authors.initials: Y
authors.lastname: Mullen
mesh_terms: D018929:Cell Culture Techniques; D002470:Cell Survival; D015925:Cryopreservation / Q000379:methods*; D004789:Enzyme Activation; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases