Abstract
Transplantation of frozen-thawed islets of Langerhans normalized urine volume, urine glucose, plasma glucose, and weight gain in diabetic rats. However, these animals had abnormal intravenous glucose tolerance tests (ivGTT) at 3 mo post-transplant. Modified cryopreservation protocols were extended to canine islet-containing tissue: a higher temperature was used during equilibration in the 2 M dimethyl sulfoxide. Recipients of frozen-thawed isografts had prolonged normoglycemia with plasma glucose <105 mg/100 ml for up to 18 mo. During ivGTT at 6 mo post-transplant, K values (decline in glucose concentration, %/min) were similar in dogs autotransplanted with fresh (K=1.22±0.37) or cryopreserved tissue (K=1.8±0.4). Because of the similar compactness of the pancreas in humans and dogs, this canine model should be useful for formulating an optimal cryopreservation technique for human islets.
Résumé
La transplantation d'îlots de Langerhans conservés par congélation normalise la diurèse, la glycosurie, la glycémie et la croissance pondérale des rats diabétiques. Cependant ces animaux ont une courbe d'hyperglycémie provoquée par voie veineuse (HGPV) anormale 3 mois après la greffe. Des modifications ont été apportées aux procédés de conservation pour leur adaptation aux îlots de chien: une température plus élevée est utilisée pour l'équilibration dans le diméthylsulfoxide 2M. Les receveurs de greffons isogéniques conservés congelés ont une normoglycémie prolongée avec une glycémie inférieure à 105 mg/100 ml pendant un temps allant jusqu'à 18 mois. Les tests d'hyperglycémie provoquée intraveineuse 6 mois après la greffe donnent des valeurs de K (baisse de la glycémie, en % par min.) similaires chez les chiens autotransplantés avec des îlots frais (K=1.22±0.37) ou conservés congelés (K=1.8±0.4). Le tissu pancréatique du chien étant aussi compact que celui de l'homme, ce modèle canin devrait aider à la mise au point d'une méthode optimale pour la conservation des îlots humains.
Resumen
El transplante de islotes de Langerhans congelados-descongelados resulta en la normalización del volumen urinario, de la glucosa urinaria, de la glucosa plasmática y de la ganancia de peso en ratas diabéticas. Sin embargo, estos animales exhiben resultados anormales en las pruebas intravenosas de tolerancia a la glucosa 3 meses después del transplante. Protocolos de criopreservación modificados han sido utilizados con tejido insular canino, usando una mayor temperatura durante el equilibrio en el 2M dimetilsulfóxido. Los animales recipientes de isotransplantes congelados-descongelados exhibieron normoglicemia prolongada, con valores de glucosa plasmática <105 mg/100 ml hasta por 18 meses. En las pruebas intravenosas de tolerancia a la glucosa realizadas 6 meses después del transplante, los valores K (declinación de la concentración de glucosa, %/min) fueron similares autotrans-plantados con tejido fresco (K=1.22±0.37) o con tejido criopreservado (K=1.8±0.4). En razón de la similitud en la densidad del páncreas humano y del páncreas canino, este modelo canino puede ser útil en la formulación de la técnica óptima de criopreservación de islotes humanos.
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Supported by grants from the Edmonton Civic Employees' Charitable Assistance Fund, The Juvenile Diabetes Research Foundation, The Alberta Heritage Foundation for Medical Research, The Medical Research Council of Canada, and The Muttart Diabetes Research and Training Centre.
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Rajotte, R.V., Warnock, G.L. & Kneteman, N.N. Cryopreservation of insulin-producing tissue in rats and dogs. World J. Surg. 8, 179–186 (1984). https://doi.org/10.1007/BF01655133
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DOI: https://doi.org/10.1007/BF01655133