Foetal pancreas transplantation in the rat
<p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">The efficacy of transplantation of foetal pancreas for correction of streptozotocin diabetes in the rat was studied using 17-18 day gestation foetal rat pancreata implanted under the renal capsule of the recipients. When 6 gr...
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
1980
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| _version_ | 1797071697172496384 |
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| author | Garvey, J |
| author2 | Morris, P |
| author_facet | Morris, P Garvey, J |
| author_sort | Garvey, J |
| collection | OXFORD |
| description | <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">The efficacy of transplantation of foetal pancreas for correction of streptozotocin diabetes in the rat was studied using 17-18 day gestation foetal rat pancreata implanted under the renal capsule of the recipients. When 6 grafts were implanted in isogeneic recipients (LEW ➝ LEW), which were treated initially with exogenous insulin, normoglycaemia was usually achieved during the second week after implantation. Mature islets developed from undifferentiated precursor cells of the graft, and normal glucose tolerance and insulin secretion were achieved in recipients when studied 3 to 6 months later.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">When foetal pancreas was allotransplanted in the weak (DA x LEW) Fl ➝ DA and strong (DA x LEW)F1 ➝ LEW combination, rejection (as determined by histological assessment of biopsied grafts) commenced by 3 days and was complete by 14 days, as evidenced by elevation of serum glucose levels. The histopathology of rejection was similar to that described for other transplanted organs: the inflammatory infiltrate consisted of small lymphocytes, plasma cells and neutrophil polymorphs together with fibrinoid necrosis of the vessels in the graft.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">The foetal rat pancreas could be successfully cultivated in vitro for 21 days, and when examined ultrastructurally, the explant contained mature beta, alpha and delta cells together with healthy Golgi complexes, mitochondria and ribosomes. When 21 day cultured explants were transplanted into diabetic isogeneic and allogeneic recipients, normoglycaemia was attained in isogeneic recipients, but allogeneic recipients never survived normoglycaemic for more than 2 days longer than recipients of non-cultured allografts. However, there was a consistent and marked reduction in lymphocytotoxic antibody titres in the recipients of cultured allografts, thus demonstrating that some reduction in graft immunogenicity was achieved. Cyclophosphamide pretreatment had little effect on prolonging survival of either foetal pancreas or isolated islet allografts, although it did reduce the amount of exocrine contamination present in the isografts.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">Recipient immunosuppression by intravenous administration of donor-specific alloantisera did not markedly prolong survival of foetal pancreas or isolated islet allografts in the (DA x LEW)F1 ➝ DA or Fl ➝ LEW combinations. Administration of a short course of antilymphocyte serum resulted in survival beyond 150 days in some recipients of foetal pancreas allografts, although interpretation of the results was complicated by regranulation of beta cells in islets in the recipient's own pancreas. The new immunosuppressive agent Cyclosporin A prolonged graft survival up to 15 days, but the survival obtained was less than that seen with isolated islets and skin allografts in the same strain combinations.</p> |
| first_indexed | 2024-03-06T22:57:03Z |
| format | Thesis |
| id | oxford-uuid:60c67cd4-4404-4736-97a6-b3671bf04ce5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:57:03Z |
| publishDate | 1980 |
| record_format | dspace |
| spelling | oxford-uuid:60c67cd4-4404-4736-97a6-b3671bf04ce52022-03-26T17:55:24ZFoetal pancreas transplantation in the ratThesishttp://purl.org/coar/resource_type/c_db06uuid:60c67cd4-4404-4736-97a6-b3671bf04ce5DiabetesPancreasGraft rejectionTransplantationEnglishPolonsky Theses Digitisation Project1980Garvey, JMorris, PMorris, P<p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">The efficacy of transplantation of foetal pancreas for correction of streptozotocin diabetes in the rat was studied using 17-18 day gestation foetal rat pancreata implanted under the renal capsule of the recipients. When 6 grafts were implanted in isogeneic recipients (LEW ➝ LEW), which were treated initially with exogenous insulin, normoglycaemia was usually achieved during the second week after implantation. Mature islets developed from undifferentiated precursor cells of the graft, and normal glucose tolerance and insulin secretion were achieved in recipients when studied 3 to 6 months later.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">When foetal pancreas was allotransplanted in the weak (DA x LEW) Fl ➝ DA and strong (DA x LEW)F1 ➝ LEW combination, rejection (as determined by histological assessment of biopsied grafts) commenced by 3 days and was complete by 14 days, as evidenced by elevation of serum glucose levels. The histopathology of rejection was similar to that described for other transplanted organs: the inflammatory infiltrate consisted of small lymphocytes, plasma cells and neutrophil polymorphs together with fibrinoid necrosis of the vessels in the graft.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">The foetal rat pancreas could be successfully cultivated in vitro for 21 days, and when examined ultrastructurally, the explant contained mature beta, alpha and delta cells together with healthy Golgi complexes, mitochondria and ribosomes. When 21 day cultured explants were transplanted into diabetic isogeneic and allogeneic recipients, normoglycaemia was attained in isogeneic recipients, but allogeneic recipients never survived normoglycaemic for more than 2 days longer than recipients of non-cultured allografts. However, there was a consistent and marked reduction in lymphocytotoxic antibody titres in the recipients of cultured allografts, thus demonstrating that some reduction in graft immunogenicity was achieved. Cyclophosphamide pretreatment had little effect on prolonging survival of either foetal pancreas or isolated islet allografts, although it did reduce the amount of exocrine contamination present in the isografts.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">Recipient immunosuppression by intravenous administration of donor-specific alloantisera did not markedly prolong survival of foetal pancreas or isolated islet allografts in the (DA x LEW)F1 ➝ DA or Fl ➝ LEW combinations. Administration of a short course of antilymphocyte serum resulted in survival beyond 150 days in some recipients of foetal pancreas allografts, although interpretation of the results was complicated by regranulation of beta cells in islets in the recipient's own pancreas. The new immunosuppressive agent Cyclosporin A prolonged graft survival up to 15 days, but the survival obtained was less than that seen with isolated islets and skin allografts in the same strain combinations.</p> |
| spellingShingle | Diabetes Pancreas Graft rejection Transplantation Garvey, J Foetal pancreas transplantation in the rat |
| title | Foetal pancreas transplantation in the rat |
| title_full | Foetal pancreas transplantation in the rat |
| title_fullStr | Foetal pancreas transplantation in the rat |
| title_full_unstemmed | Foetal pancreas transplantation in the rat |
| title_short | Foetal pancreas transplantation in the rat |
| title_sort | foetal pancreas transplantation in the rat |
| topic | Diabetes Pancreas Graft rejection Transplantation |
| work_keys_str_mv | AT garveyj foetalpancreastransplantationintherat |