Skip to main content
padlock icon - secure page this page is secure

Adult porcine islet transplantation in baboons treated with conventional immunosuppression or a non-myeloablative regimen and CD154 blockade

Buy Article:

$59.00 + tax (Refund Policy)

The aim of the present study was to assess the survival of adult porcine islets transplanted into baboons receiving either (1) conventional triple drug immunosuppressive therapy or (2) a non-myeloablative regimen and an anti-CD154 monoclonal antibody (mAb) aimed at tolerance-induction.

Group 1 baboons (n=3) were pancreatectomized prior to intraportal injection of 10 000 porcine islet equivalents (IE)/kg and immunosuppressed with anti-thymocyte globulin (ATG), cyclosporine and azathioprine. In Group 2 (n=2), non-pancreatectomized baboons underwent induction therapy with whole body and thymic irradiation, and ATG. Extracorporeal immunoadsorption (EIA) of anti-Galα1,3Gal (Gal) antibody was carried out. Maintenance therapy was with cobra venom factor, cyclosporine, mycophenolate mofetil, methylprednisolone and anti-CD154 mAb. Porcine islets were injected intraportally (14 000 and 32 000 IE/kg, respectively) and high-dose pig mobilized peripheral blood progenitor cells (3 × 1010 cells/kg) were infused into a systemic vein. Porcine islets were also implanted in the sternomastoid muscle to facilitate subsequent biopsies. In both groups, porcine C-peptide was measured, and histological examination of liver or sternomastoid muscle biopsies was performed at regular intervals.

In Group 1, total pancreatectomy reduced human C-peptide to < 0.1 ng/ml and induced insulin-requiring diabetes. The transplantation of porcine islets was followed by normalization of glycemia for 15–24 h. Porcine C-peptide was detected only transiently immediately after porcine islet injection (maximum 0.12 ng/ml). Histological examination of liver biopsies taken between days 2 and 19 did not reveal viable islets, but necrotic cell structures with mononuclear cell infiltrates were identified in portal venules. In Group 2, injection of porcine islets into non-pancreatectomized recipients induced a transient hypoglycemia (2–4 h) requiring concentrated intravenous dextrose administration. Porcine C-peptide was detectable for 5 and 3 days (maximum 2.8 and 1.0 ng/ml), respectively. Baboon #4 died on day 12 from small bowel intussusception. Liver and sternomastoid muscle biopsies showed well-preserved porcine islets, staining positive for insulin and glucacon, without signs of rejection. In baboon #5, viable islets were detected in the sternomastoid muscle biopsy on day 14, but not on day 28 or thereafter. A progressive mononuclear cell and macrophage infiltration was seen in the biopsies. In conclusion, conventional immunosuppression allowed survival of porcine islets in baboons for < 24 h. The non-myeloablative regimen prolonged survival of porcine islets for > 14 days. However, despite depletion of T cells, anti-Gal antibody and complement, and CD154-blockade, porcine islets were rejected by day 28. These results suggest that powerful innate immune responses are involved in rejection of discordant xenogeneic islets.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: anti-CD154 monoclonal antibody; diabetes; islets of Langerhans; pancreatectomy; pig-to-primate model; xenotransplantation

Document Type: Research Article

Affiliations: 1: Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, USA, 2: Clinique de Chirurgie Digestive, Hopital Cantonal Universitaire de Genève, Switzerland, 3: Joslin Diabetes Center/Harvard Medical School, Boston, USA, 4: Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, USA, 5: Transplant Unit, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, USA, 6: Department of Renal and Pancreatic Transplantation and Pathology, University of Louvain, Brussels, Belgium, 7: Immerge BioTherapeutics, Inc., Charlestown, USA

Publication date: January 1, 2002

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more