We have recently demonstrated that swine bone marrow cells (BMC) can e
ngraft in C.B-17 scid mice. While engraftment is enhanced by providing
donor-specific porcine cytokines, the level of swine hematopoiesis de
clines between 3 and 6 weeks post-transplant. In the present study, th
e utility of several strains of immunodeficient mice as recipients of
swine hematopoietic cells has been determined by comparing levels of s
wine bone marrow engraftment at 3 weeks after bone marrow transplant.
Irradiated recipients were injected with 1x10(8) swine BMC and were tr
eated daily with porcine cytokines. The presence of swine cells in BMT
recipients was detected by flow cytometry and marrow colony-forming a
ssays. Recombination activating gene-1 (RAG-l)-deficient mice were not
permissive for the engraftment of swine BMC, even with administration
of increased doses of whole body irradiation, or with depleting anti-
NK cell antibody. In contrast, NOD-scid mice showed improved swine BMC
engraftment compared to C.B-17 scid mice. Levels of swine class I+, m
yeloid, and CD2(+) cells in bone marrow, spleen, and peripheral blood,
and the number of porcine myeloid progenitor cells was significantly
higher in NOD-scid recipients than in simultaneous C.B-17 scid recipie
nts, In addition, the sera from C.B-17 scid mice markedly inhibited th
e proliferation of swine BMC in vitro., A weaker inhibitory effect was
also mediated by sera from RAG-1-deficient! mice, but not by sera fro
m NOD-scid mice. Together, our results indicate that multiple host ele
ments resist xenogeneic hematopoietic engraftment and function, some o
f which are clearly independent of host T, B, or NK cells. Understandi
ng the basis for the advantage of NOD-scid mice as recipients of disco
rdant xenogeneic porcine BMC will help to identify these elements.