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Adult pancreatic tissue fate after pancreatic fragment autotransplantation into the spleen of the pancreatectomized dog

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Abstract

As far as we know, after adult enzyme-digested pancreatic fragment autotransplantation, the fate of the inoculated pancreatic tissue has never been reported and the hypothetic engrafted islet mass growth by mitotic division or by a true islet neogenesis from ductular precursor cells has never been demonstrated. In dogs with total or near-total (90%) pancreatectomy that preserves the duodenum and the common bile duct, morphologic study of the pancreatic tissue inoculated into the spleen has demonstrated an exuberant ductular-acinar-islet regenerative process, with progressive cystic degeneration of the newly formed ductular-acinar structures occurring simultaneously with the selective survival and growing predominance of extraductal tissue scattered as distinct islets, clusters of islet cells, or single islet cells. In addition to the B, A2, and D cell types of the normal adult dog islet, we have also seen a peculiar ultrastructural pleomorphism of the insular B cells, frequently combined with their ductular or glandular arrangement in maturing islets. Rare or never before reported islet cell types in the adult dog's islets (G cells, mixed endocrine cells of the A2-D, D-B, and A2-B types, and mixed acinar-islet cells of the D-acinar type) were also putatively identified. Using light microscopy we have identified many mitotic figures on ductular and centroacinar cells in ductules and ductular-acinar structures. Moreover, we have ultrastructurally characterized a pluriendocrine nesidioblastic process identified in the most common islet cell types (B, A2, D) and in G cells and mixed acinar islet cells of the B-ac, A2-ac, D-ac, F-ac, and G-ac types as well as “intermediary” or “transitional” cells of incipient ductular-acinar, ductular-islet, and ductular-acinar-islet differentiation. The characteristics of the extraductal islet tissue and the exuberant nesidioblastic process have demonstrated neogenesis of islets and islet cells from precursor ductular cells at several points after the autotransplant, and we suggest that this mechanism may be of fundamental importance for the engrafted islet mass growth—keeping in mind the age of the pancreatic tissue donors and the life-span of the juvenile diabetic recipient receiving the transplant. This evolution has taken place simultaneously with the progressive rarefaction of the regenerated ductular-acinar structures definitively deprived of an intestinal drainage route by virtue of their heterotopic location.

Resumen

Hasta donde sabemos, después del autotrasplante de fragmentos pancreáticos enzimáticamente digeridos, no se ha reportado la evolución final del tejido pancreático inoculado; y el crecimiento de la hipotética masa del tejido insular trasplantado, por división mitótica a por verdadera neogénesis de islotes a partir de células ductales precursoras, nunca ha sido demostrado.

En el perro sometido a pancreatectomía total o casi total (90%) con preservación del duodeno y del colédoco, el estudio morfológico del tejido pancreático inoculado en el bazo ha demostrado un exuberante proceso regenerativo de células dactulares-acinares-insulares-, con progresiva degeneración quística de las neoformadas estructuras ductulares-acinares simultánea con la sobrevida selectiva y el crecimiento predominante del tejido insular a partir de ductos, y de células insulares aisladas o en grupos. Además de los tipos B, A2 y D de las células insulares del perro, también hemos podido identificar un peculiar pleomorfismo ultraestructural de las células insulares B, con frecuencia combinado con su ordenación ductular o glandular en los islotes en vía de maduración. También fueron putativamente identificados tipos celulares muy raros o nunca reportados en los islotes caninos (células G, células endocrinas mixtas de los tipos A2/D, D/B, Y A2/B, y células mixtas acinares e insulares del tipo D-acinar). En las estructuras ductulares y ductular-acinares hemos podido reconocer muchas figuras mitóticas en células ductulares y centroacinares mediante microscopia de luz y un proceso pluriendocrino nesidio-blástico con la identificación netraestructural de los tipos más comunes de células insulares (B, A2, D), pero también células G y células mixtas acinar-insulares de los tipos B-ac, A2-ac, D-ac, F-ac y G-ac, así como células “intermedias” o “transicionales” de la incipiente diferenciación ductular-acinar, ductular-insular, y ductular-acinar-insular. Las caracteristicas del tejido insular originado en ductos y el exuberante proceso nesidioblástico han demostrado la neogénesis de células insulares y de islotes a partir de células precursoras en diferentes períodos después del autotrasplante; nosotros sugerimos que este mecanismo puede ser de importancia fundamental para el crecimiento de la masa insular trasplantada, teniendo en cuenta la edad de los donantes de tejido pancreático y la duración de la vida de los recipientes diabéticos y juveniles. Esta evolución ha cursado con una progresiva rarefacción de las estructuras ductulares-acinares, definitivamente desprovista de una vía de drenaje intestinal debido a su ubicación heterotópica.

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Authors and Affiliations

  1. Department of Surgery, University of Oporto School of Medicine, Apartado 2282, 4204, Porto Codex, Portugal

    Mário L. C. Madureira M.D., Ph.D.

  2. Department of Pathology, University of Oporto School of Medicine, Apartado 2282, 4204, Porto Codex, Portugal

    Mário L. C. Madureira M.D., Ph.D.

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Madureira, M.L.C. Adult pancreatic tissue fate after pancreatic fragment autotransplantation into the spleen of the pancreatectomized dog. World J. Surg. 18, 259–265 (1994). https://doi.org/10.1007/BF00294411

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