Skip to main content
SpringerLink
Log in

Lymphoid activation by micro-and macroencapsulated islets during mixed lymphocyte islet culture

  • Originals
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

We have recently demonstrated long-lasting normoglycaemia after transplantation of barium alginate microencapsulated rat and porcine islets. Nevertheless the transplantation results obtained with different microencapsulation techniques have been controversial. Little is known about possible immune interactions between host and encapsulated islet. This study demonstrates in vitro stimulation of lymphoid cells by encapsulated islets that is similar to that of unencapsulated islets. This stimulation was reduced by a 4-day culture with unencapsulated islets only. After macroencapsulation of islets in hollow fibres a stimulatory effect was also observed, but this was less pronounced than after microencapsulation. Empty microcapsules as well as macrocapsules induced lymphoid proliferation as a result of mitogenic impurities in the encapsulation materials themselves. In the same donor-recipient combination in which we have shown successful transplantation, we found activation of the sensibilization arm of the immune system. This suggests that microencapsulation results in protection of the transplanted islets from the action of the effector arm. This lymphoid activation could be triggered by the mitogeniticity of the encapsulation material itself. In the case of alginates these mitogenic factors could not be abolished by culture (i.e. dialysis).

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

References

  1. Zekorn T, Horcher A, Siebers U, Schnettler R, Klöck G, Hering B, Zimmermann U, Bretzel RG, Federlin K, Barium-cross-linked alginate beads: a simple, one-step method for successful immunoisolated transplantation of islets of Langerhans. Acta Diabetol 29:99–106, 1992

    Google Scholar 

  2. Kröncke K-D, Funda J, Berschick B, Kolb H, Kolb-Bachofen V, Macrophage cytotoxicity towards isolated rat islet cells: neither lysis nor its protection by nicotinamide are beta-cell specific. Diabetologia 34:232–238, 1991

    Google Scholar 

  3. Gotoh M, Maki T, Kiyoizumi T, Satomi S, Monaco AP, An improved method for isolation of mouse pancreatic islets. Transplantation 40:437–438, 1985

    Google Scholar 

  4. Flesch B, Entenmann H, Milde K, Bretzel RG, Federlin K, Islet transplantation in experimental diabetes of the rat. XIII. Cryopreservation reduces MHC class II but not class I antigens of rat pancreatic islets. Horm Metab Res 23:1–6, 1991

    Google Scholar 

  5. Zekorn T, Renardy M, Planck H, Zschocke P, Bretzel RG, Siebers U, Federlin K, Experiments on a new hollow fiber membrane for immunoisolated transplantation of islets of Langerhans. Horm Metab Res [Suppl 25]: 202–206, 1990

  6. London NJM, Contractor H, Lake SP, Aucott GC, Bell PRF, James RFL, A fluorometric viability assay for single human and rat islets. Horm Metab Res [Suppl 25]:82–87, 1990

    Google Scholar 

  7. Altman JJ, Houlbert D, Callard P, McMillan P, Solomon BA, Rosen J, Galletti PM, Long-term plasma glucose normalization in experimental diabetic rats with macroencapsulated implants of benign human insulomas. Diabetes 35:625–633, 1986

    Google Scholar 

  8. Darqui S, Chicheportiche D, Cappron F, Boitard C, Reach G, Comparative study of microencapsulated rat islets implanted in different diabetic models in mice. Horm Metab Res [Suppl 25]: 209–213, 1990

  9. Fritschy WM, Strubbe JH, Wolters GHJ, Schilfgaarde R van, Glucose tolerance and plasma insulin response to intravenous glucose infusion and test meal in rats with microencapsulated islets allografts. Diabetologia 34:542–547, 1991

    Google Scholar 

  10. Maki T, Uhbi C, Sanchez-Farpon H, Sullivan SJ, Borland K, Muller TE, Solomon BA, Chick WL, Monaco AP, Successful treatment of diabetes with the biohybrid artificial pancreas in dogs. Transplantation 51:43–51, 1991

    Google Scholar 

  11. Mazaheri R, Atkinson P, Stiller C, Dupre J, Vose J, O'Shea G, Transplantation of encapsulated allogeneic islets into diabetic BB/W rats. Transplantation 51:750–754, 1991

    Google Scholar 

  12. Lacy PE, Hegre O, Gerasimidi-Vazeou A, Gentile FT, Dionne K, Maintenance of normoglycemia in diabetic mice by subcutaneous xenografts of encapsulated islets. Science 254:1782–1784, 1991

    Google Scholar 

  13. Theodorou NA, Easterbrook, Tyhurst M, Howell SL, Islets of Langerhans in diffusion chambers do not initiate antibody production. Transplantation 31:90–91, 1979

    Google Scholar 

  14. Horcher A, Zekorn T, Siebers U, Bretzel RG, Zimmermann U, Federlin K, Insulin release from different models of a bioartificial pancreas (microencapsulation vs. macroencapsulation vs. alginate coating) (abstract). Cell Transplantation 1:175, 1992

    Google Scholar 

  15. Pueyo ME, Darqui S, Capron F, Reach G, In vitro activation of human macrophages by alginate-polylysine-microcapsules (abstract). Diabetologia 35 [Suppl 1]:188, 1992

    Google Scholar 

  16. Weber C, Zabinski S, Norton J, Koschitzki T, D'Agati V, Reemtsma K, The future role of microencapsulation in xenotransplantation. In: Hardy MA (ed) Xenograft 25. Excerpta Medica, Amsterdam, pp 297–308, 1989

    Google Scholar 

  17. Halle J-P, Leblond F-A, Landry D, Fournier A, Chevalier S, Arginine esterase release by microencapsulated prostatic cells as a measure of membrane permeability to proteins (abstract). Cell Transplantation 1:166, 1992

    Google Scholar 

  18. Soon-Shiong P, Lu Z-N, Grewal I, Lanza R, Clark W, Prevention of CTL and NK cell-mediated cytotoxicity by microencapsulation. Horm Metab Res [Suppl 25]:215–219, 1990

    Google Scholar 

  19. Cole DR, Waterfall M, McIntyre M, Baird JD, Microencapsulated islet grafts in the BB/E rat: a possible role for cytokines in graft failure. Diabetologia 35:231–237, 1992

    Google Scholar 

  20. Christenson L, Aebischer P, McMillan P, Galletti PM, Tissue reaction to intraperitoneal polymer implants: species difference and effects of corticoid and doxirubicin. J Biomed Mater Res 23:705–718, 1989

    Google Scholar 

  21. Miller KM, Rose-Caprara V, Anderson JM, Generation of IL-1-like activity in response to biomedical polymer implants: comparison of in vitro and in vivo models. J Biomed Mater Res 23:1007–1026, 1989

    Google Scholar 

  22. Zekorn T, Siebers U, Bretzel RG, Renardy M, Planck H, Zschocke P, Federlin K, Protection of islets of Langerhans from interleukin-1 toxicity by artificial membranes. Transplantation 50:391–394, 1990

    Google Scholar 

  23. Chicheportiche D, Walker R, Baird J, In vivo activation of peritoneal macrophages by implantation of alginate-polylysine-alginate microcapsules in the BB-rat (abstract). Diabetologia 34 [Suppl 2]:170, 1991

    Google Scholar 

  24. Zimmermann U, Klöck G, Federlin K, Hannig K, Kowalski M, Bretzel RG, Horcher A, Entenmann H, Siebers U, Zekorn T, Production of mitogen-contamination-free alginates with variable ratios of mannuronic acid to guluronic acid by free flow electrophoresis. Electrophoresis 13:269–274, 1992

    Google Scholar 

  25. Baier RE, The organization of blood components near interfaces. In: Vroman L, Leonard EF (eds) The behaviour of blood and its components at interfaces. Ann NY Acad Sci 283:17–36, 1977

  26. Ritz E, Andrassy K, Bommer J, Rauterberg E, Protein layer formation on artificial membranes. Contrib Nephrol 59:80–89, 1987

    Google Scholar 

  27. Darquy S, Reach G, Immunoisolation of pancreatic B cells by microencapsulation. Diabetologia 28:776–780, 1985

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Klinik III und Poliklinik, Justus-Liebig-Universität, Rodthohl 6, D-35385, Giessen, Germany

    T. Zekorn, H. Entenmann, A. Horcher, U. Siebers, K. Federlin & R. G. Bretzel

  2. Institut für Biotechnologie der Universität, Am Hubland, D-97074, Würzburg, Germany

    G. Klöck & U. Zimmermann

Authors
  1. T. Zekorn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Entenmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Horcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. U. Siebers
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Klöck
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. U. Zimmermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K. Federlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R. G. Bretzel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zekorn, T., Entenmann, H., Horcher, A. et al. Lymphoid activation by micro-and macroencapsulated islets during mixed lymphocyte islet culture. Acta Diabetol 30, 238–242 (1993). https://doi.org/10.1007/BF00569935

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00569935

Key words

Search

Navigation