Neonatal induction of tolerance to skeletal tissue allografts without immunosuppression

Vascularized allogeneic skeletal tissue transplantation without the need fo r host immunosuppression would increase reconstructive options for treating congenital and acquired defects. Because the immune system of a fetus or n eonate is immature, it may be possible to induce tolerance to allogeneic sk eletal tissues by alloantigen injection during this permissive period. With in 12 hours after birth, 17 neonatal Lewis rats were injected through the s uperficial temporal vein with 3.5 to 5 million Brown Norway hone marrow cel ls in 0.1 mi normal saline. Ten weeks after the injection, peripheral blood from the Lewis rats was analyzed for the presence of Brown Norway cells to determine hemopoietic chimerism. The Lewis rats chen received a heterotopi c, vascularized limb tissue transplant (consisting of the knee, the distal femur, the proximal tibia, and the surrounding muscle on a femoral vascular pedicle) from Brown Norway rat donors to determine their tolerance to the allogeneic tissue. A positive control group (n = 6) consisted of syngeneic transplants from Lewis rats into naive Lewis rats to demonstrate survival o f transplants. A negative control group (n = 6) consisted of Brown Norway t ransplants into naive Lewis rats not receiving bone marrow or other immunos uppressive treatment. The animals were assessed for transplant viability 30 days after transplantation using histologic and bone fluorochrome analysis . All the syngeneic controls (Lewis to Lewis) remained viable throughout th e experiment, whereas all the Brown Norway to Lewis controls had rejected. Ten of the 17 allografts transplanted into bone marrow recipients were viab le at 30 days, with profuse bleeding from the ends of the bone graft and th e surrounding graft muscle. The percent of chimerism correlated with surviv al, with 3.31 percent (SD = 1.9) of peripheral blood, Brown Norway chimeris m present in the prolonged survival groups and 0.75 percent (SD = 0.5) of B rown Norway chimerism in the rejected graft group. This study demonstrated prolonged survival of allogeneic skeletal tissue without immunosuppression after early neonatal injection of allogeneic bone marrow in a rat model.