Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience

Tatiana Froud, Camillo Ricordi, David Baidal, Muhammad M. Hafiz, Gaston Ponte, Pablo Cure, Antonello Pileggi, Raffaella Poggioli, Hirohito Ichii, Aisha Khan, Jacqueline V. Ferreira, Alberto Pugliese, Violet V. Esquenazi, Norma S Kenyon, Rodolfo Alejandro

Research output: Contribution to journalArticle

273 Citations (Scopus)

Abstract

Following the success obtained with transplantation of fresh human islets under steroid-free immunosuppression, this trial evaluated the transplantation of islets that had undergone a period of in vitro culture and the potential of tumor necrosis factor (TNF-α) blockade to improve islet engraftment. Subjects included 16 patients with type 1 diabetes mellitus (T1DM); half were randomly assigned to receive Infliximab immediately preceding initial infusion. Immunosuppression consisted of daclizumab induction and sirolimus/tacrolimus maintenance. Out of 16 subjects 14 achieved insulin independence with one or two islet infusions; adverse events precluded completion in two. Without supplemental infusions, 11/14 (79%) subjects were insulin independent at 1 year, 6/14 (43%) at 18 months; these same subjects remain insulin independent at 33 ± 6 months. While on immunosuppression, all patients maintained graft function. Out of 14 patients, 8 suffered chronic partial graft loss, likely immunological in nature, 5 of these received supplemental infusions. Currently, 11 subjects remain on immunosuppression, 8 (73%) are insulin independent, two with supplemental infusions. Insulin independent subjects demonstrated normalization of HbA1c, fructosamine and Mean Amplitude of Glycemic Excursions (MAGE) values. No clinical benefit of infliximab was identified. These results demonstrate that transplantation of cultured human islet allografts results in reproducible insulin independence in all subjects under this immunosuppressive regimen, comparable to that of freshly transplanted islets (Edmonton protocol).

Original languageEnglish
Pages (from-to)2037-2046
Number of pages10
JournalAmerican Journal of Transplantation
Volume5
Issue number8
DOIs
StatePublished - Aug 1 2005

Fingerprint

Islets of Langerhans Transplantation
Type 1 Diabetes Mellitus
Immunosuppression
Steroids
Insulin
Transplantation
Fructosamine
Transplants
Tacrolimus
Sirolimus
Immunosuppressive Agents
Allografts
Tumor Necrosis Factor-alpha
Maintenance

Keywords

  • Autoimmunity
  • Engraftment
  • FK506
  • Graft function
  • Graft survival
  • Humanized antibodies
  • Immunosuppression
  • Insulin
  • Islets
  • Preservation solutions
  • Sirolimus (SLR)
  • Transplantation
  • Tumor necrosis factor (TNF)

ASJC Scopus subject areas

  • Immunology

Cite this

Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression : Miami experience. / Froud, Tatiana; Ricordi, Camillo; Baidal, David; Hafiz, Muhammad M.; Ponte, Gaston; Cure, Pablo; Pileggi, Antonello; Poggioli, Raffaella; Ichii, Hirohito; Khan, Aisha; Ferreira, Jacqueline V.; Pugliese, Alberto; Esquenazi, Violet V.; Kenyon, Norma S; Alejandro, Rodolfo.

In: American Journal of Transplantation, Vol. 5, No. 8, 01.08.2005, p. 2037-2046.

Research output: Contribution to journalArticle

Froud, Tatiana ; Ricordi, Camillo ; Baidal, David ; Hafiz, Muhammad M. ; Ponte, Gaston ; Cure, Pablo ; Pileggi, Antonello ; Poggioli, Raffaella ; Ichii, Hirohito ; Khan, Aisha ; Ferreira, Jacqueline V. ; Pugliese, Alberto ; Esquenazi, Violet V. ; Kenyon, Norma S ; Alejandro, Rodolfo. / Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression : Miami experience. In: American Journal of Transplantation. 2005 ; Vol. 5, No. 8. pp. 2037-2046.
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AU - Ponte, Gaston

AU - Cure, Pablo

AU - Pileggi, Antonello

AU - Poggioli, Raffaella

AU - Ichii, Hirohito

AU - Khan, Aisha

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