Foetal rat pancreatic transplantation: posttransplantation development of foetal pancreatic iso- and allografts and suppression of rejection with mycophenolate mofetil (MMF) and cyclosporine based immunesuppression.
Provided engraftment can be ensured, vascularization promoted, and ischaemic damage due to storage prevented, foetal pancreatic transplantation (FPT) has the potential to ameliorate the endocrine and metabolic disturbances in diabetic animal models including hyperglycaemia. In a syngeneic Wistar rat substrain (WAG) model (WAG --> WAG), FPT was capable of restoring normoglycaemia in diabetic rats rendered diabetic by streptozotocin (STZ). Posttransplantation growth and development of the foetal tissue was characterised by acinar atrophy, preservation of islet tissue, and development and proliferation of fat accumulations at the site of engraftment. B- and A-cell staining and distribution on ICC appeared normal after 12 months. Mycophenolate mofetil (MMF) together with cyclosporine (CSA) was selected to suppress rejection of foetal rat pancreatic allografts in a strong responder allogeneic model (WAG --> Sprague-Dawley). MMF, a novel immunosuppressive agent that selectively inhibits de novo purine synthesis, was administered in combination with subtherapeutic doses of CSA (2 mg/kg/day) to prevent rejection after allogeneic foetal rat pancreatic transplantation. Although CSA monotherapy in this model can partially suppress rejection, the combination of CSA and MMF results in significant inhibition of acute allograft rejection and mononuclear cellular (MNC) infiltration as assessed by sequential histology post-operatively. Although the follow-up period of allografts was restricted to 30 days of treatment, histology showed low graft infiltrate scores (1.2+) and preservation of islets and immunocytochemical staining. The results in this animal transplantation model confirm that sub-therapeutic doses of MMF and CSA therapy are effective in preventing acute rejection of foetal rat pancreatic allografts in the short-term, thus allowing preservation of vital endocrine components of the foetal pancreas such as islets.
du Toit
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D
Department of Anatomy and Histology, Faculty of Medicine, University of Stellenbosch Medical School, Tygerberg, South Africa. mcdb@maties.sun.ac.za
Muller
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C
Page
B
B
Louw
J
J
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D004359:Drug Therapy, Combination; D016332:Fetal Tissue Transplantation / Q000276:immunology / Q000473:pathology; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D010179:Pancreas / Q000196:embryology; D016035:Pancreas Transplantation / Q000276:immunology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid