Engraftment of discordant xenogeneic swine bone marrow cells in immunodeficient mice

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Abstract
We have recently demonstrated that swine bone marrow cells (BMC) can engraft in C.B‐17 scid mice. While engraftment is enhanced by providing donor‐specific porcine cytokines, the level of swine hematopoiesis declines between 3 and 6 weeks post‐transplant. In the present study, the utility of several strains of immunodeficient mice as recipients of swine hematopoietic cells has been determined by comparing levels of swine bone marrow engraftment at 3 weeks after bone marrow transplant. Irradiated recipients were injected with lxlO8 swine BMC and were treated daily with porcine cytokines. The presence of swine cells in BMT recipients was detected by flow cytometry and marrow colony‐forming assays. Recombination activating gene‐1 (RAG‐1)‐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+, myeloid, 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 recipients. In addition, the sera from C.B‐17 scid mice markedly inhibited the proliferation of swine BMC in vitro. A weaker inhibitory effect was also mediated by sera from RAG‐1‐deficient mice, but not by sera from NOD‐scid mice. Together, our results indicate that multiple host elements resist xenogeneic hematopoietic engraftment and function, some of which are clearly independent of host T, B, or NK cells. Understanding the basis for the advantage of NODscid mice as recipients of discordant xenogeneic porcine BMC will help to identify these elements.