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Sustained human hematopoiesis in sheep transplanted in utero during early
gestation with fractionated adult human bone marrow cells
EF Srour, ED Zanjani, JE Brandt, T Leemhuis, RA Briddell, NA Heerema and R Hoffman
Division of Hematology/Oncology, Indiana University School of Medicine,
Indianapolis 46202-5121.
Sheep were transplanted in utero during early gestation with subpopulations
of adult human bone marrow (BM) cells enriched for human progenitor and
hematopoietic stem cells (HSC). Chimerism was documented in three of seven
transplanted fetuses using monoclonal antibodies against human-specific
hematopoietic cell lineages and/or cytogenetic analysis of BM and
peripheral blood cells of recipients. Only chimeric sheep BM cells
expressing CD45 (6.0% of total BM cells) formed human hematopoietic
colonies in response to human recombinant cytokines as determined by
cytogenetic analysis. Sorted CD45+ BM cells developed human T-cell colonies
containing CD3+, CD4+, and CD8+ cells. DNA from chimeric BM cells obtained
3 months after birth displayed a finger printing pattern identical to that
of DNA from the human donor of the HSC graft. These studies indicate that
first trimester sheep fetuses are tolerant of adult human HSC grafts, thus
permitting the creation of xenogeneic chimera expressing human myeloid and
lymphoid lineages. The present findings also suggest that HSC grafts from
immunologically competent, HLA-mismatched adult donors may be useful for
correcting human genetic diseases in utero during early gestation.
Volume 79,
Issue 6,
pp. 1404-1412,
03/15/1992
Copyright © 1992 by The American Society of Hematology
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