Yg. Yang et al., DONOR-SPECIFIC GROWTH-FACTORS PROMOTE SWINE HEMATOPOIESIS IN SEVERE COMBINED IMMUNE-DEFICIENT MICE, Xenotransplantation, 3(1), 1996, pp. 92-101
Induction of a state of mixed hematopoietic chimerism following bone m
arrow transplantation is associated with donor-specific tolerance in t
he concordant xenogeneic rat-to-mouse species combination. We are now
attempting to induce such tolerance in a discordant species combinatio
n, pig to mouse. Our initial studies showed that non-immune physiologi
c factors limited the level of swine hematopoietic reconstitution in s
evere combined immune deficient (SCID) mice. We have now examined the
ability of swine-specific growth factors, interleukin-3 (IL-3), granul
ocyte macrophage-colony stimulating factor (GM-CSF), and stem cell fac
tor (SCF) to enhance repopulation by swine bone marrow cells in SCID r
ecipients. The results indicate that swine IL-3 promotes pig hematopoi
esis in SCID mouse recipients. The percentage of swine class I+ cells
in bone marrow, spleen, and peripheral blood was markedly increased by
a 3-week treatment course with porcine IL-3. In longer-term studies,
the effect of IL-3 was further enhanced by combining it with porcine G
M-CSF. Almost all repopulating porcine cells expressed a swine myeloid
marker. Colony-forming assays showed a correlation of the number of p
ig-specific colonies with the number of swine cells detected by flow c
ytometry in transplanted-SCID bone marrow recipients. Porcine CD2(+) c
ells which did not express CD4 or CD8 coreceptors were also detected i
n SCID mouse recipients of pig bone marrow, and their numbers were als
o increased by swine cytokine treatment. Swine IgG, but not B cells we
re detected in SCID recipients at 3 and 6 weeks following bone marrow
transplantation, and declined over time, suggesting that mature B cell
s engrafted, but that de novo B lymphopoiesis did not occur in these m
ice. Thus, our study demonstrates that donor-specific growth factors c
an help to overcome the physiologic barrier to xenogeneic hematopoiesi
s in the discordant pig to mouse species combination.