Combined neonatal blood transplants in a parent-to-F1 mouse model: improved survival rates and stable long-term engraftment.

The use of cord blood (CB) transplantation for adult patients is limited by the relatively low cell content of a single collection. Two, partially-matched CB grafts could provide optimal cell doses. The interactions among the donor-derived populations have not been fully evaluated. We used our mouse model (Neonatal peripheral blood--NPB--transplants to adult recipients) to evaluate whether grafts from two histocompatibility-disparate donors ("combined" grafts) had higher survival and faster hematopoietic recovery than single donor transplants, each at suboptimal cell dose (leading to survival <60%). Transplants were performed in a parent-to-F1 setting: NPB or bone marrow (BM) cells from the fully mismatched, homozygous parental strains (A/J, B6) were given to myeloablated B6AF1 recipients. Outcomes improved by combining NPB grafts: 48% of A/J graft recipients (1 x 10(6) cells/animal) survived; all animals transplanted with B6 (same cell dose) died. Survival after combined NPB transplants was 75% (P < 0.01) and recipients had accelerated recovery of WBCs and platelets compared to single donor A/J grafts (P < 0.01). No such improvements occurred with suboptimal dose combined BM transplants. Recipients of combined NPB grafts reconstituted with one donor primarily. Chimerism levels remained stable. Successful secondary transplants demonstrated long-term persistence of both NPB grafts. Combined haplo-identical NPB but not BM grafts, each transplanted at suboptimal cell doses, engraft synergistically leading to faster reconstitution. Although the mouse model does not fully represent the complex clinical aspects of human transplantation, our findings support the concept of using two CB grafts for adult patients when a sufficiently large single one is not available.