Improving efficacy of clinical islet transplantation with iodixanol-based islet purification, thymoglobulin induction, and blockage of IL-1β and TNF-α

Shinichi Matsumoto, Morihito Takita, Damien J. Chaussabel, Hirofumi Noguchi, Masayuki Shimoda, Koji Sugimoto, Takeshi Itoh, Daisuke Chujo, Jeff Sorelle, Nicholas Onaca, Bashoo Naziruddin, Marlon F. Levy

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Abstract

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.

Original languageEnglish
Pages (from-to)1641-1647
Number of pages7
JournalCell Transplantation
Volume20
Issue number10
Publication statusPublished - 2011
Externally publishedYes

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Keywords

  • Interleukin-1β (IL-1β)
  • Islet transplantationl
  • Single donor
  • Thymoglobulin
  • Tumor necrosis factor-α (TNF-α)

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Matsumoto, S., Takita, M., Chaussabel, D. J., Noguchi, H., Shimoda, M., Sugimoto, K., Itoh, T., Chujo, D., Sorelle, J., Onaca, N., Naziruddin, B., & Levy, M. F. (2011). Improving efficacy of clinical islet transplantation with iodixanol-based islet purification, thymoglobulin induction, and blockage of IL-1β and TNF-α. Cell Transplantation, 20(10), 1641-1647.