TY - JOUR
T1 - Improving efficacy of clinical islet transplantation with iodixanol-based islet purification, thymoglobulin induction, and blockage of IL-1β and TNF-α
AU - Matsumoto, Shinichi
AU - Takita, Morihito
AU - Chaussabel, Damien
AU - Noguchi, Hirofumi
AU - Shimoda, Masayuki
AU - Sugimoto, Koji
AU - Itoh, Takeshi
AU - Chujo, Daisuke
AU - Sorelle, Jeff
AU - Onaca, Nicholas
AU - Naziruddin, Bashoo
AU - Levy, Marlon F.
PY - 2011
Y1 - 2011
N2 - Poor efficacy is one of the issues for clinical islet transplantation. Recently, we demonstrated that pancreatic ductal preservation significantly improved the success rate of islet isolation; however, two transplants were necessary to achieve insulin independence. In this study, we introduced iodixanol-based purification, thy-moglobulin induction, and double blockage of IL-1β and TNF-α as well as sirolimus-free immunosuppres-sion to improve the efficacy of clinical islet transplantation. Nine clinical-grade human pancreata were procured. Pancreatic ductal preservation was performed using ET-Kyoto solution in all cases. When the isolated islets met the clinical criteria, they were transplanted. We utilized two methods of immunosuppression and anti-inflammation. The first protocol prescribed daclizumab for induction, then sirolimus and tacrolimus to main-tain immunosuppression. The second protocol used thymoglobulin for induction and tacrolimus and mycophe-nolate mofetil to maintain immunosuppression. Eternacept and anakinra were administered as anti-inflammatory drugs. The total amount of insulin required, HbA1c, and the SUITO index were determined to analyze and compare the results of transplantation. All isolated islet preparations (9/9) met the criteria for clinical transplantation, and they were transplanted into six type 1 diabetic patients. All patients achieved insulin independence with normal HbA1c levels; however, the first protocol required two islet infusions (N = 3) and the second protocol only required a single infusion (N = 3). The average SUITO index, at 1 month after a single-donor islet transplantation, was significantly higher in the second protocol (49.6 ± 8.3 vs. 19.3 ± 6.3, p<0.05). Pancreatic ductalpreservation, iodixanol-based purification combinedwith thymoglobulin induc-tion, and blockage of IL-1β and TNF-α as well as sirolimus-free immunosuppression dramatically improved the efficacy of clinical islet transplantations. This protocol enabled us to perform successful single-donor islet transplantations. Further large-scale studies are necessary to confirm these results and clarify the mecha-nism of each component.
AB - Poor efficacy is one of the issues for clinical islet transplantation. Recently, we demonstrated that pancreatic ductal preservation significantly improved the success rate of islet isolation; however, two transplants were necessary to achieve insulin independence. In this study, we introduced iodixanol-based purification, thy-moglobulin induction, and double blockage of IL-1β and TNF-α as well as sirolimus-free immunosuppres-sion to improve the efficacy of clinical islet transplantation. Nine clinical-grade human pancreata were procured. Pancreatic ductal preservation was performed using ET-Kyoto solution in all cases. When the isolated islets met the clinical criteria, they were transplanted. We utilized two methods of immunosuppression and anti-inflammation. The first protocol prescribed daclizumab for induction, then sirolimus and tacrolimus to main-tain immunosuppression. The second protocol used thymoglobulin for induction and tacrolimus and mycophe-nolate mofetil to maintain immunosuppression. Eternacept and anakinra were administered as anti-inflammatory drugs. The total amount of insulin required, HbA1c, and the SUITO index were determined to analyze and compare the results of transplantation. All isolated islet preparations (9/9) met the criteria for clinical transplantation, and they were transplanted into six type 1 diabetic patients. All patients achieved insulin independence with normal HbA1c levels; however, the first protocol required two islet infusions (N = 3) and the second protocol only required a single infusion (N = 3). The average SUITO index, at 1 month after a single-donor islet transplantation, was significantly higher in the second protocol (49.6 ± 8.3 vs. 19.3 ± 6.3, p<0.05). Pancreatic ductalpreservation, iodixanol-based purification combinedwith thymoglobulin induc-tion, and blockage of IL-1β and TNF-α as well as sirolimus-free immunosuppression dramatically improved the efficacy of clinical islet transplantations. This protocol enabled us to perform successful single-donor islet transplantations. Further large-scale studies are necessary to confirm these results and clarify the mecha-nism of each component.
KW - Interleukin-1β (IL-1β)
KW - Islet transplantationl
KW - Single donor
KW - Thymoglobulin
KW - Tumor necrosis factor-α (TNF-α)
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U2 - 10.3727/096368910X564058
DO - 10.3727/096368910X564058
M3 - Article
C2 - 21396171
AN - SCOPUS:79957525661
SN - 0963-6897
VL - 20
SP - 1641
EP - 1647
JO - Cell Transplantation
JF - Cell Transplantation
IS - 10
ER -