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Transplantation of cryopreserved human pancreatic islets into diabetic nude mice

Abstract

If pancreatic islet transplantation becomes clinically applicable, cryogenic storage of human islet preparations could solve many problems related to transportation and banking of islets, HLA matching, recipient pretreatment, or the possible use of multiple donors. The diabetic nude mouse could offer a simple model to test in vivo the function of cryopreserved human islet preparations before transplantation into diabetic patients.

In this study, 6 nude mice made diabetic by an intravenous injection of streptozocin were transplanted with 400–600 cryopreserved human islets beneath the renal capsule. All the mice became normoglycemic within 3 weeks from transplantation. Nephrectomy of the kidneys bearing the grafts 45 days after transplantation resulted in an immediate return to the diabetic state, demonstrating that the only functional tissue was located in the excised kidneys. Histologic study of the renal subcapsular grafts demonstrated morphologic integrity of the islets with a normal degree of beta granulation.

The results demonstrated that cryopreserved human islets will function in diabetic nude mice. This model to test human islet preparations in vivo may be of assistance in the application of cryopreserved islet transplantation in diabetic patients.

Résumé

Si la transplantation des ilôts pancréatiques devient un jour applicable cliniquement, le stockage cryogénique des préparations d'ilôts humains pourrait résoudre bien des problèmes concernant le transport et la banque d'ilôts, l'appariement HLA, le prétraitaient du receveur ou la possibilité d'utiliser plusieurs donneurs. La souri nude diabétique est un modèlein vivo simple pour tester la fonction des préparation des ilôts humaines avant de pratiquer la transplantation chez le diabétique.

Dans cette étude, on a pratiqué la transplantation de 400–600 ilôts humains conservés au froid sous la capsule rénale chez 6 souris nude, rendues diabétiques par injection intraveineuse de Streptozotocine. Toutes les souris sont redevenues normoglycémiques en moins de 3 semaines. La néphrectomie des reins portant les greffons 45 jours après a provoqué immédiatement le retour à l'état diabétique, démontrant la qualité fonctionnelle des seuls ilôts transplantés. L'étude histologique des greffons sous capsulaires a montré l'intégrité morphologique des ilôts avec un taux normal de granulation bétâ.

Ces résultats prouvent que les ilôts humains conservés fonctionnent bien chez la souri-nude diabétique. Ce modèle pour tester les préparationsin vivo peut servir d'aide dans l'application de la transplantation d'ilôts conservés au froid chez le diabétique.

Resumen

Si el trasplante de islotes pancreáticos se hace clínicamente aplicable, la criopreservación de preparaciones de islotes pancreáticos humanos podría resolver muchos de los problemas relacionados con el transporte y almacenamiento de tales islotes, con la compatibilización HLA, con el pretratamiento del receptor, y con el posible uso de multiples donantes. El ratón atímico diabético puede representar un modelo sencillo para probarin vivo la función de preparaciones criopreservadas de islotes humanos antes de ser trasplantadas a pacientes diabéticos.

En el presente estudio 6 ratones atímicos hechos diabéticos mediante la inyección intravenosa de estreptozotocina, fueron trasplantados con 400–600 islotes humanos criopreservados al tejido subcapsular renal a través de una incisión en la cápsula del riñón. Todos los ratones convirtieron a normoglicemia dentro de las primeras 3 semanas después del trasplante. La nefrectomía del riñón portador de los islotes, realizada a los 45 días del trasplante, resultó en el retorno inmediato al estado diabéticos, demostrando así que el único tejido funcional estaba representado por los islotes trasplantados al riñón. El estudio histológico de los trasplantes renales subcapsulares demostró morfología normal de los islotes con grado normal de granulación de tipo beta.

Nuestros resultados demuestran que los islotes criopreservados funcionan en trasplantes al ratón atímico. Este modelo escogido para probar el funcionamiento de preparaciones de islotesin vivo puede ser de utilidad en la aplicación práctica del trasplante de islotes pancreáticos criopreservados en pacientes diabéticos.

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Author information

Correspondence to Dr. Paul E. Lacy M.D., Ph.D..

Additional information

Supported in part by NIH Training Program Grant No. 5T32A107163; Brown and Williamson Tobacco Corporation, Philip Morris Incorporated, R.J. Reynolds Tobacco Company and United States Tobacco Company; Project Transplant; The Humana Foundation; and the PJD Fund.

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Ricordi, C., Kneteman, N.M., Scharp, D.W. et al. Transplantation of cryopreserved human pancreatic islets into diabetic nude mice. World J. Surg. 12, 861–864 (1988). https://doi.org/10.1007/BF01655500

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Keywords

  • Pancreatic Islet
  • Streptozotocine
  • Human Islet
  • Islet Transplantation
  • Renal Capsule