Comparison of ulinastatin, gabexate mesilate, and nafamostat mesilate in preservation solution for islet isolation.
For islet transplantation, maintaining organ viability after pancreas procurement is critically important for optimal graft function and survival. We recently reported that islet yield was significantly higher in the modified ET-Kyoto (MK) solution, which includes a trypsin inhibitor  (ulinastatin), compared with the UW solution, and that the advantages of MK solution are trypsin inhibition and less collagenase inhibition. In this study, we compared ulinastatin with other trypsin inhibitors, gabexate mesilate, and nafamostat mesilate, in preservation solution for islet  isolation. Ulinastatin was easily dissolved in ET-Kyoto solution, while ET-Kyoto with gabexate mesilate and nafamostat mesilate became cloudy immediately after addition. Although there were no significant differences in islet yield among the three groups, viability was significantly higher  for the MK group than for the GK group or the NK group. The stimulation index was significantly higher for the MK group than for the GK group. In summary, there are no other trypsin inhibitors that are more effective than ulinastatin. Based on these data, we now use ET-Kyoto solution with  ulinastatin for clinical islet transplantation.
Baylor All Saints Medical Center, Baylor Research Institute, Fort Worth, TX, USA. noguchih2006@yahoo.co.jp
Hirofumi
H
Noguchi
Bashoo
B
Naziruddin
Andrew
A
Jackson
Masayuki
M
Shimoda
Yasutaka
Y
Fujita
Daisuke
D
Chujo
Morihito
M
Takita
Han
H
Peng
Koji
K
Sugimoto
Takeshi
T
Itoh
Naoya
N
Kobayashi
Michiko
M
Ueda
Teru
T
Okitsu
Yasuhiro
Y
Iwanaga
Hideo
H
Nagata
Xiaoling
X
Liu
Hiroki
H
Kamiya
Nicholas
N
Onaca
Marlon F
MF
Levy
Shinichi
S
Matsumoto
D000818:Animals; D001550:Benzamidines; D002469:Cell Separation / Q000379:methods*; D002470:Cell Survival / Q000187:drug effects; D016670:Gabexate / Q000737:chemistry / Q000494:pharmacology*; D005942:Gluconates / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry / Q000494:pharmacology*; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology*; D006895:Hydroxyethyl Starch Derivatives / Q000737:chemistry; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects; D010710:Phosphates / Q000737:chemistry; D013552:Swine; D014199:Trehalose / Q000737:chemistry; D014357:Trypsin / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000494:pharmacology
D001550:Benzamidines; C087059:ET-Kyoto solution; D005942:Gluconates; D006023:Glycoproteins; D006146:Guanidines; D006895:Hydroxyethyl Starch Derivatives; D010710:Phosphates; D014361:Trypsin Inhibitors; D016670:Gabexate; D014199:Trehalose; D014357:Trypsin; C028665:urinastatin; C032855:nafamostat