title: The influence of immune system stimulation on encapsulated islet graft survival.
abstract: BACKGROUND
  The aim of this study was to determine the influence activating of the recipient immune system on the function of microencapsulated islet xenografts.
  
  
  METHODS
  The skin of WAG or Fisher rats and WAG free or encapsulated (APA) Langerhans islets were transplanted to healthy or to streptozotocin diabetic BALB/c mice. Skin grafts were performed following the method of Billingham and Medawar. Rat islets were isolated from pancreas by the Lacy and Kostianovsy method and encapsulated with calcium alginate-poly-L-lysine-alginate according to the 3-step coating method of Sun.
  
  
  RESULTS
  The transplantation of encapsulated WAG islets, despite activation of the host immune system, restored euglycemia for over 180 +/-100 days. A subsequent skin graft taken from the same donor was rejected in the second set mode, but euglycemia persisted. In diabetic recipients, impaired immune response was corrected by successful encapsulated islet transplantation. In diabetic mice, strong stimulation with 2-fold skin transplantation induced primary non-function of grafted islets despite their encapsulation.
  
  
  CONCLUSIONS
  The survival of an islet xenograft depends on the level of activation of the recipient immune system. The immune response of diabetic mice was impaired, but increased after post-transplant restitution of euglycemia. Microencapsulation sufficiently protected grafted islets, and remission of diabetes was preserved. However, after strong specific or non-specific stimulation of the host immune system, non-function of xenografted islets developed despite their encapsulation. Therefore, islet graft recipients should avoid procedures which could stimulate their immune systems. If absolutely necessary, the graft should be protected by exogenous insulin therapy at that time.
authors.affiliation: Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland. torlowski@mediclub.pl
authors.forename: Tadeusz M
authors.initials: TM
authors.lastname: Orłowski
authors.forename: Ewa
authors.initials: E
authors.lastname: Godlewska
authors.forename: Magda
authors.initials: M
authors.lastname: Tarchalska
authors.forename: Joanna
authors.initials: J
authors.lastname: Kinasiewicz
authors.forename: Magda
authors.initials: M
authors.lastname: Antosiak
authors.forename: Marek
authors.initials: M
authors.lastname: Sabat
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology / Q000601:surgery; D004339:Drug Compounding; D006085:Graft Survival / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D016038:Skin Transplantation / Q000276:immunology; D014183:Transplantation, Heterologous
chemical_list: D001786:Blood Glucose