The long-term survival of baboon-to-monkey kidney and liver xenografts.
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 1,076 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.
Zhong
Robert
R
Department of Surgery, The University of Western Ontario, Canada. zzhong@uwo.ca
Tucker
Jane
J
Zhang
Zheng
Z
Wall
William
W
Grant
David
D
Quan
Douglas
D
Garcia
Bertha
B
Gao
Zu-Hua
ZH
Asfar
Sami
S
Sharpe
Michael
M
Gelb
Adrian
A
Bailey
Michele
M
Stiller
Calvin
C
D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010215:Papio; D020123:Sirolimus / Q000627:therapeutic use; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
D000910:Antibodies, Heterophile; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D020123:Sirolimus; D008775:Methylprednisolone