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

M. Ramirez, G. A. Rottman, L. D. Shultz, C. I. Civin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)332-344
Number of pages13
JournalExperimental Hematology
Volume26
Issue number4
StatePublished - 1998

Fingerprint

Colony-Forming Units Assay
Stem Cells
Bone Marrow
Tissue Donors
T-Lymphocytes
Thymus Gland
Population
Immunoglobulins
Lymphoid Progenitor Cells
Chimerism
Hematopoiesis
Graft vs Host Disease

Keywords

  • Hematopoietic stem cells
  • Immunodeficient mice
  • SCID mouse assays
  • Xenogeneic hematopoietic chimeras

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Mature human hematopoietic cells in donor bone marrow complicate interpretation of stem/progenitor cell assays in xenogeneic hematopoietic chimeras. / Ramirez, M.; Rottman, G. A.; Shultz, L. D.; Civin, C. I.

In: Experimental Hematology, Vol. 26, No. 4, 1998, p. 332-344.

Research output: Contribution to journalArticle

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