Liver transplantation without immunosuppression: future perspectives.
It has been hypothesized that a state of microchimerism in recipients of organ transplants may result in donor-specific tolerance to the graft. Numerous studies show that infusion of donor-derived bone marrow cells can, indeed, achieve systemic chimerism in the recipient and effectively prolong allograft survival. We have compared organ and patient survival in recipients of liver allografts alone (controls) or in combination with single or multiple infusions of donor bone marrow cells; recipients were infused either at day 0 (perioperatively) or at day 0 and 11 post-transplant. The incidence of rejection episodes and survival of the liver allograft were significantly reduced in recipients of two bone marrow infusions compared to controls; recipients of one infusion, conversely, experienced a higher number of rejection episodes when compared to controls, pointing to a possible sensitizing role of a single bone marrow infusion if administered perioperatively. Variables such as timing, number and composition of the bone marrow inocula still remain to be elucidated but may be of critical importance for the attainment of a state of donor-specific tolerance without the need for immunosuppressive therapy in recipients of organ allografts.
Selvaggi
G
G
Diabetes Research Institute, Cell Transplant Center, Miami, FL 33136, USA.
Ricordi
C
C
Bottino
R
R
Tzakis
A G
AG
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D016031:Liver Transplantation / Q000276:immunology*; D014019:Tissue Donors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous