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The long‐term survival of baboon‐to‐monkey kidney and liver xenografts *
Author(s) -
Zhong Robert,
Tucker Jane,
Zhang Zheng,
Wall William,
Grant David,
Quan Douglas,
Garcia Bertha,
Gao Zuhua,
Asfar Sami,
Sharpe Michael,
Gelb Adrian,
Bailey Michele,
Stiller Calvin
Publication year - 2003
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1034/j.1399-3089.2003.02054.x
Subject(s) - baboon , kidney , medicine , urology , cyclophosphamide , regimen , renal function , immunosuppression , pharmacology , gastroenterology , chemotherapy
The present study was undertaken to develop an optimum immunosuppressive regimen in baboon‐to‐monkey life‐supporting kidney xenografts. Baseline therapy for all groups include cyclosporine (CsA) and steroids. We compared adding (1) cyclophosphamide (CyP) at dose of 20 mg/kg/day given on post‐operative day (POD) 0, 2, 5 and 7; (2) mycophenolic mofetil (MMF) at a dose of 40 mg/kg/day by daily gavage; or (3) CyP + rapamycin (Rap). The latter group was divided into high and low dose subgroups. Untreated xenografts were rejected on POD 6, CsA alone treated xenografts survived for 35 days and CsA + CyP treated xenografts survived for 45 days. Adding MMF significantly prolonged mean survival to 111 ± 53 days, but the xenografts eventually developed rejection. Combination therapy including CsA, CyP and Rap reliably prevented xenogenic rejection and achieved a mean survival of 290 ± 30 days. However, high dose CyP + Rap led to high incidence of post‐transplant lymphoproliferation disorders (PTLD), while the incidence of PTLD was significantly less in the low dose subgroup ( P < 0.01). Four animals in this subgroup survived for more than 300 days with normal renal function and histology. In addition, two liver recipients treated with CsA + CyP survived for 91 and 1076 days. We conclude that long‐term survival of kidney or liver xenografts can be achieved in a non‐human concordant xenograft model using currently available immunosuppressive agents.