Vascularized islet cell transplantation in miniature swine: Islet-kidney allografts correct the diabetic hyperglycemia induced by total pancreatectomy

Naoki Kumagai, John C. LaMattina, Chisako Kamano, Parsia A. Vagefi, Rolf N. Barth, John J. O'Neil, Shin Yamamoto, Shannon G. Moran, Ryu Utsugi, David H. Sachs, Kazuhiko Yamada

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We have previously reported the preparation of vascularized islet-kidneys (IKs) by transplantation of islets under the autologous kidney capsule. Here, we compare the efficacy of transplanting vascularized versus nonvascularized islets into diabetic allogeneic swine recipients. In the vascularized islet transplantation (5,000 islet equivalents [IE]/kg), recipients received minor-mismatched (n = 4) or fully-mismatched (n = 2) IKs after pancreatectomy, with a 12-day course of cyclosporine A (CyA) or FK506, respectively. For the nonvascularized islet transplantation (7,000 IE/kg), three recipients received minor-mismatched islets alone and two recipients received minor-mismatched donor islets placed in a donor kidney on the day of transplantation. All recipients of nonvascularized islets were treated with a 12-day course of CyA. With vascularized islet transplantation, pancreatectomized recipients were markedly hyperglycemic pretransplant (fasting blood glucose >300 mg/dl). After composite IK transplantation, all recipients developed and maintained normoglycemia (<120 mg/dl) and stable renal function indefinitely (>3 months), and insulin therapy was not required. Major histocompatibility complex-mismatched recipients demonstrated in vitro donor-specific unresponsiveness. In contrast, recipients of nonvascularized islets remained hyperglycemic. In conclusion, IK allografts cured surgically induced diabetes across allogeneic barriers, whereas nonvascularized islet transplants did not. These data indicate that prevascularization of islet allografts is crucial for their subsequent engraftment and that composite IKs may provide a strategy for successful islet transplantation.

Original languageEnglish (US)
Pages (from-to)3220-3228
Number of pages9
JournalDiabetes
Volume51
Issue number11
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

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Miniature Swine
Islets of Langerhans Transplantation
Pancreatectomy
Cell Transplantation
Islets of Langerhans
Hyperglycemia
Allografts
Kidney
Kidney Transplantation
Cyclosporine
Tacrolimus
Major Histocompatibility Complex
Capsules
Blood Glucose
Fasting
Swine
Transplantation
Insulin
Transplants

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Vascularized islet cell transplantation in miniature swine : Islet-kidney allografts correct the diabetic hyperglycemia induced by total pancreatectomy. / Kumagai, Naoki; LaMattina, John C.; Kamano, Chisako; Vagefi, Parsia A.; Barth, Rolf N.; O'Neil, John J.; Yamamoto, Shin; Moran, Shannon G.; Utsugi, Ryu; Sachs, David H.; Yamada, Kazuhiko.

In: Diabetes, Vol. 51, No. 11, 01.11.2002, p. 3220-3228.

Research output: Contribution to journalArticle

Kumagai, N, LaMattina, JC, Kamano, C, Vagefi, PA, Barth, RN, O'Neil, JJ, Yamamoto, S, Moran, SG, Utsugi, R, Sachs, DH & Yamada, K 2002, 'Vascularized islet cell transplantation in miniature swine: Islet-kidney allografts correct the diabetic hyperglycemia induced by total pancreatectomy', Diabetes, vol. 51, no. 11, pp. 3220-3228. https://doi.org/10.2337/diabetes.51.11.3220
Kumagai, Naoki ; LaMattina, John C. ; Kamano, Chisako ; Vagefi, Parsia A. ; Barth, Rolf N. ; O'Neil, John J. ; Yamamoto, Shin ; Moran, Shannon G. ; Utsugi, Ryu ; Sachs, David H. ; Yamada, Kazuhiko. / Vascularized islet cell transplantation in miniature swine : Islet-kidney allografts correct the diabetic hyperglycemia induced by total pancreatectomy. In: Diabetes. 2002 ; Vol. 51, No. 11. pp. 3220-3228.
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AU - Yamamoto, Shin

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AU - Sachs, David H.

AU - Yamada, Kazuhiko

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