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

Research output: Contribution to journalArticle

76 Citations (Scopus)

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

Fingerprint

Islets of Langerhans Transplantation
Insulin
Interleukin-1
Purification
Immunosuppression
Sirolimus
Tacrolimus
Transplants
Transplantation
Tissue Donors
Interleukin 1 Receptor Antagonist Protein
Pancreas
Anti-Inflammatory Agents
iodixanol
thymoglobulin
Inflammation
Pharmaceutical Preparations

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

Improving efficacy of clinical islet transplantation with iodixanol-based islet purification, thymoglobulin induction, and blockage of IL-1β and TNF-α. / Matsumoto, Shinichi; Takita, Morihito; Chaussabel, Damien J.; Noguchi, Hirofumi; Shimoda, Masayuki; Sugimoto, Koji; Itoh, Takeshi; Chujo, Daisuke; Sorelle, Jeff; Onaca, Nicholas; Naziruddin, Bashoo; Levy, Marlon F.

In: Cell Transplantation, Vol. 20, No. 10, 2011, p. 1641-1647.

Research output: Contribution to journalArticle

Matsumoto, S, Takita, M, Chaussabel, DJ, Noguchi, H, Shimoda, M, Sugimoto, K, Itoh, T, Chujo, D, Sorelle, J, Onaca, N, Naziruddin, B & Levy, MF 2011, 'Improving efficacy of clinical islet transplantation with iodixanol-based islet purification, thymoglobulin induction, and blockage of IL-1β and TNF-α', Cell Transplantation, vol. 20, no. 10, pp. 1641-1647.
Matsumoto, Shinichi ; Takita, Morihito ; Chaussabel, Damien J. ; Noguchi, Hirofumi ; Shimoda, Masayuki ; Sugimoto, Koji ; Itoh, Takeshi ; Chujo, Daisuke ; Sorelle, Jeff ; Onaca, Nicholas ; Naziruddin, Bashoo ; Levy, Marlon F. / Improving efficacy of clinical islet transplantation with iodixanol-based islet purification, thymoglobulin induction, and blockage of IL-1β and TNF-α. In: Cell Transplantation. 2011 ; Vol. 20, No. 10. pp. 1641-1647.
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