Skip to main content
SpringerLink
Log in

In-vitro- und In-vivo-Studien zur Isolierung, Transplantation und Funktion von Langerhans-Inseln am Schwein

In vitro and in vivo studies for isolation, transplantation and function of islets of Langerhans in pigs

  • Originalarbeiten
  • Published:
Langenbecks Archiv für Chirurgie Aims and scope Submit manuscript

Summary

Limits and possibilities of the transplantation of islets of Langerhans in pigs were studied. 6 × 104 to 3 × 106 islets and insulin producing fragments per pancreas were obtained by intraductal collagenase digestion of the pancreatic gland following total pancreatectomy. Islets grafted into the spleen or liver rendered normoglycemia to the pancreatectomized animals as demonstrated by normal fasting blood sugars and normal intravenous glucose tolerance tests as compared to not operated animals permitting a survival time of up to one year. Apancreatic controls died of ketoacidosis and diabetic coma 10 to 12 days posttransplant. The number of isolated and transplanted islets correlated well to the normoglycemic state of the animal. Beyond that the in vitro challenge of the islets with glucose and resulting insulin secretion was a very important indicator for the functional status and integrity of the islets after transplantation. Thus the pig appears to be a suitable model for the preclinical studying of islet transplantation especially since immunologic, physiologic and anatomic features of the pig are similar to those in the human regarding pancreas and nutrition.

Zusammenfassung

Grenzen und Möglichkeiten der Transplantation von Langerhans-Inseln wurden am Schwein erprobt. Nach totaler Pankreatektomie wurden durch intraduktale Kollagenaseandauung zwischen 6mal 104 and 3mal 106 Inseln and inseltragende Fragmente pro Pankreas gewonnen. Nach Injektion des Transplantates in die Milz oder wahlweise in die Leber konnte bei den Tieren ein normoglykämischer Zustand mit normalen intravenösen Glukosetoleranztesten und ein Überleben bis zu 1 Jahr erreicht werden. Apankreatische Kontrollen verstarben im diabetischen Koma 10–12 Tage postoperativ. Eine gute Korrelation zwischen der Anzahl transplantierter Inseln und Normoglykämie nach Transplantation konnte demonstriert werden. Darüber hinaus war die synchrone In-vitro-Stimulation der Inseln mit Glukose und die daraus resultierende Inselsekretion ein wichtiger Indikator für die funktionelle Integrität der Inseln nach der Transplantation. Das Schwein bietet somit auch aufgrund der dem Menschen sehr ähnlichen immunologischen, physiologischen und anatomischen Eigenschaften bezüglich des Pankreas und der Ernährung ein gutes Modell zur weiteren präklinischen Erforschung der Inseltransplantation als Therapie des Diabetes mellitus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Literatur

  1. Alejandro R, Shienvold FL, Hagek SV, Ryan U, Miller J, Mintz DH (1982) Immunocytochemical localization of HLA-DR in human islets of Langerhans. Diabetes 31 [Suppl 4]:17–22

    Article  PubMed  Google Scholar 

  2. Bustad LK, McClellan RD (1966) Swine in biomedical research. Pacific Northwest Laboratory, Richland

    Google Scholar 

  3. Cobb LF, Merrell RC (1984) Total pancreatectomy in dogs. J Surg Res 37:235

    Article  CAS  PubMed  Google Scholar 

  4. Faustman D, Hauptfeld V, Lacy P, Davie J (1981) Prolongation of marine islet allograft survival by pretreatment of islet with antibody directed to la determinants. Proc Natl Acad Sci USA 78:5156–5159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gäbel H, Bitter-Suermann H, Heniksen C, Säve-Söderberg J, Lundholm K, Brynger H (1985) Streptozotocin diabetes in juvenile pigs. Evaluation of an experimental model. Horm Metab Res 17:275–280

    Article  PubMed  Google Scholar 

  6. Getty R (1975) The anatomy of domestic animals. Saunders, Philadelphia

    Google Scholar 

  7. Gores PF, Mayoral H, Field MJ, Sutherland DER (1986) Comparison of immunogenicity of purified and unpurified murine islet allografts. Transplantation 41:529–531

    Article  CAS  PubMed  Google Scholar 

  8. Grace DM, Feindel CMS, Harris KA, Inculet RI, Wallace AC, Stiller CR (1982) Immune response to transplanted pancreas in pig. Transplant Proc 14:649–655

    CAS  PubMed  Google Scholar 

  9. Gray DWR, Millard PR, McShane P, Morris PJ (1983) The use of the dye neural red as a specific, non-toxic, intra-vital stain of islets of Langerhans. Br J Exp Pathol 64:553–558

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Gray DWR, Morris PJ (1987) Developments in isolated pancreatic islet transplantation. Transplantation 43:321–331

    Article  CAS  PubMed  Google Scholar 

  11. Hansen WA, Christie MR, Kahn R et al. (1989) Supravital dithizone staining in the isolation of human and rat pancreatic islets. Diabetes Res 10:53–57

    CAS  PubMed  Google Scholar 

  12. Hesse UJ, Sutherland DER, Florack G, Field J, Ward S, Najarian JS (1986) Comparison of two methods of islet preparation and transplantation in dogs. Diabetes 35:1109–1118

    Article  CAS  PubMed  Google Scholar 

  13. Horaguchi A, Merrel RC (1981) Preparation of viable islet cells from dogs by a new method. Diabetes 30:455–458

    Article  CAS  PubMed  Google Scholar 

  14. Kanai T, Gotoh M, Porter J, Monaco AP, Maki T (1988) Multiple donor composite and sequential allografts: a new approach to pancreatic islet transplantation. Transplant Proc 20(1):891–893

    Google Scholar 

  15. Kiviluoto T (1985) Transplantation of pancreatic microfragments in totally pancreatectomized pigs. Eur Surg Res 17:119–127

    Article  CAS  PubMed  Google Scholar 

  16. Kryiakides GK, Nutial FQ, Miller J (1979) Segmental pancreatic transplantation in pigs. Surgery 85:151–158

    Google Scholar 

  17. Merrell RC, Maeda M, Basadonna G, Marincola F, Cobb L (1985) Suppression, stress and accomodation of transplanted islets of Langerhans. Diabetes 34:667–670

    Article  CAS  PubMed  Google Scholar 

  18. Moorehouse JA, Grahame GR, Rosen NJ (1964) Relationship between intravenous glucose tolerance and fasting blood glucose level in healthy and diabetic subjects. J Clin Endocrinol 24:145–159

    Article  Google Scholar 

  19. Munn SR, Kaufmann DB, Field MJ, Viste AB, Sutherland DER (1989) Cold storage preservation of the canine and rat pancreas prior to islet isolation. Transplantation 47:28–31

    Article  CAS  PubMed  Google Scholar 

  20. Munn SR, Kaufmann DB, Meloche RM, Field MJ, Viste AB, von der Hem LG, Sutherland DER (1989) Outcome of intrahepatic canine islet autotransplantation predicted by weight corrected islet count. Diabetes 38 [Suppl 1]:306

    Google Scholar 

  21. Needham JM, Godwin KL, Miller BHR, Bewick M, Compton FJ, Winter M (1984) Disseminated intravascular coagulation after dispersed pancreas transplantation in dogs: causative agents. Transplantation 36:348–349

    Google Scholar 

  22. Pond WG, Haupt KA (1978) The biology of the pig. Constock, Ithaen

    Google Scholar 

  23. Ricordi C, Finke EH, Lacy PE (1986) A method for the mass isolation of islets from the adult pig pancreas. Diabetes 35:649–653

    Article  CAS  PubMed  Google Scholar 

  24. Sachs DH, Leight G, Cone J, Schwarz S, Stuart L, Rosenberg S (1976) Transplantation in miniature swine. I. Fixation of the major histocompatibility complex. Transplantation 22:559–567

    Article  CAS  PubMed  Google Scholar 

  25. Sack WO (1982) Essential of pig anatomy. Veterinary Textbook, Ithaca

    Google Scholar 

  26. Shienvold FL, Alejandro R, Mintz H (1986) Ia bearing cells in islets of Langerhans. Transplantation 41:364–472

    Article  CAS  PubMed  Google Scholar 

  27. Sutherland DER, Steffes MW, Bauer GE, McManus D, Noe BD, Najarian JS (1974) Isolation of human and porcine islet of Langerhans and islet transplantation in pigs. J Surg Res 16:102–111

    Article  CAS  PubMed  Google Scholar 

  28. Swindle MM (1984) Swine as replacements for dogs in the surgical teaching and research laboratory. Lab Anim Sci 34:383–385

    CAS  PubMed  Google Scholar 

  29. Traverso LW, Richard R, Gomez BS (1982) Hemodynamic measurements after administration of aprotinin and/or heparin during pancreatic cell autotransplantation in the dog, pig and monkey. Ann Surg 195:479–485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Van der Vliet JA, Meloche RM, Field MJ, Chen D, Kaufman DB, Sutherland DER (1988) Pancreatic islet isolation in rats with ductal collagenase distension, stationary digestion, and dextran separation. Transplantation 45:493–495

    Article  PubMed  Google Scholar 

  31. Van Hoorn WA, Vinik AI, van Hoorn-Hickmann R (1978) A comparison of two methods of orthotopic pancreas transplantation in the pig. Transplantation 26:287–291

    Article  PubMed  Google Scholar 

  32. Warnock GL, Majotte RV (1988) Critical mass of purified islets that induce normoglycemia after implantation into dogs. Diabetes 37:467–470

    Article  CAS  PubMed  Google Scholar 

  33. Wilson D, Phal Dhull D, Simeonovic CJ, Lafferty KJ (1986) Introduction and management of diabetes mellitus in pig. Aust J Exp Biol Med Sci 64:489–500

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chirurgische Universitätsklinik Köln-Lindenthal, Joseph-Stelzmann-Straße 9, D-5000, Köln 41

    U. J. Hesse, J. Danis, J. Weyer & G. Meyer

  2. Stipendiat der Alexander-von-Humboldt-Stiftung, Humboldt, Germany

    J. Danis

  3. Institut für Experimentelle Medizin, Universität zu Köln, Köln, Germany

    S. Saad

Authors
  1. U. J. Hesse
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Danis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Weyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Saad
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Unterstützt durch die Deutsche Forschungsgemeinschaft He1390/2

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hesse, U.J., Danis, J., Weyer, J. et al. In-vitro- und In-vivo-Studien zur Isolierung, Transplantation und Funktion von Langerhans-Inseln am Schwein. Langenbecks Arch Chir 375, 259–265 (1990). https://doi.org/10.1007/BF00184165

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00184165

Key words

Search

Navigation