Mature human hematopoietic cells in donor bone marrow complicate interpretation of stem/progenitor cell assays in xenogeneic hematopoietic chimeras.
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 cell-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.
Ramírez
M
M
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rottman
G A
GA
Shultz
L D
LD
Civin
C I
CI
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000818:Animals; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002455:Cell Division; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D016130:Immunophenotyping; D008562:Membrane Glycoproteins; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009244:NAD+ Nucleosidase / Q000032:analysis; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1