Long-term survival of rat cardiac allografts by intrathymic plus portal venous injections of donor bone marrow cells and short-term tacrolimus immunosuppression.
Intrathymic (IT) or portal venous (PV) injection of donor antigens has been shown to prolong organ acceptance in low responder rat strain combinations. We determined whether a combination of these strategies would prolong cardiac allograft survival in high responder combinations. Wistar Furth rats received 1 x 10(8) ACI rat bone marrow cells (BMCs) via IT, intravenous (IV), PV, IV + PV, IT + IV or IT + PV route at the time of ACI cardiac transplantation. Without tacrolimus (FK), all grafts were acutely rejected. With FK immunosuppression (1.5 mg/kg per day, I. M., days 0-4), single BMC injection did not increase graft survival beyond 93 days, whereas 70% of grafts survived indefinitely ( > 150 days) when IT and PV BMCs were combined. Animals receiving IT and PV BMCs also had less allograft vasculopathy. Thus, IT and PV injections of donor BMCs under a brief course of FK synergistically improve cardiac allograft survival.
Fukada
J
J
Department of Surgery, University of Miami School of Medicine, Jackson Memorial Hospital, 1611 N.W. 12th Avenue, Miami, Florida 33136, USA.
Kurimoto
Y
Y
Ruiz
P
P
Aitouche
A
A
Zeevi
A
A
Li
S
S
Kubota
T
T
Pham
S M
SM
D000818:Animals; D016026:Bone Marrow Transplantation; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011920:Rats, Inbred WF; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016559:Tacrolimus