Mature human hematopoietic cells in donor bone marrow complicate interpretation of stem/progenitor cell assays in xenogeneic hematopoietic chimeras

被引:0
|
作者
Ramírez, M
Rottman, GA
Shultz, LD
Civin, CI
机构
[1] Johns Hopkins Univ, Sch Med, Div Pediat Oncol, Dept Oncol, Baltimore, MD USA
[2] Johns Hopkins Univ, Sch Med, Div Pediat Oncol, Dept Pediat, Baltimore, MD USA
[3] Jackson Lab, Bar Harbor, ME 04609 USA
关键词
hematopoietic stem cells; immunodeficient mice; xenogeneic hematopoietic chimeras; SCID mouse assays;
D O I
暂无
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Xenogeneic hematopoietic chimeras have been used to assay the growth and differentiation of human stem/progenitor cells. The presence of human hematopoietic cells in immunodeficient mice transplanted with human marrow cells may be caused by proliferation and differentiation of early stem/progenitor cells and/or proliferation of mature cells. Unpurified human marrow mononuclear cells, T cell-depleted, or stem/progenitor cell-enriched (CD34(+) or CD34(+)CD38(-)) populations were injected into sublethally irradiated NOD/LtSz scid/scid (NOD/SCID) mice. High levels of human cells were detected in mice (hu/mu chimeras) transplanted with each of the above human marrow populations. Large numbers of mature human T lymphocytes were found in marrow, spleens, and thymuses from hu/mu chimeras that: had been transplanted with unpurified human mononuclear marrow cells. Human immunoglobulin was detected in sera from these chimeras, and some exhibited a clinical syndrome suggestive of graft-versus-host disease. In contrast, in hu/mu chimeras that had received T cell-depleted or stem/progenitor tell-enriched populations, multilineage hematopoiesis (myeloid, B lymphoid, and progenitor cells by immunophenotype) was detected but T lymphocytes and human immunoglobulin were not; in addition, no human cells were detected in the thymuses. Thus, injection of adult human marrow cells into immunodeficient mice can result in hematopoietic chimerism for at least 3 months after transplant. However, the types of cells present in hu/mu chimeras differ depending on the human cell population transplanted. This should be taken into account when hematopoietic chimeras are used to assess human stem/progenitor cell function.
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页码:332 / 344
页数:13
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