Enrichment of hematopoietic stem cell activity among human fetal liver cells expressing CD4

M. O. Muench, M. G. Roncarolo, R. Namikawa

Research output: Contribution to journalArticlepeer-review

Abstract

CD4 antigen expression was observed on human fetal liver, fetal bone marrow +"i. To test whether or not hematopoietic stem cells (HSC) express CD4, we analyzed the cell surface phenotype and functional properties of CD4+ and CD4 cells found among the CD34++ fraction of fetal liver cells. The CD4+ fraction was found to be enriched by 1.9-fold in high-proliferative potential colony-forming cells (HPP-CFC) relative to the CD4' fraction. In 7 days of fytokine-stimulaled liquid culture, the CD4+ fraction was found to generate a higher number of CD34+ cells as well as 6-fold greater number of secondary HPP-CFC than the CD4' fraction. Both the CD4+ and the CD4" subpopulations also gave rise to multilineage engraftment upon transplantation into human fetal bone fragments, supportive of B-lymphoid and myeloid growth, or into human fetal thymic fragmenis, supportive of T cell growth, implanted in xcid/scul (SCID-hu) mice. However, in SCID-hu mice transplanted with graded doses of donor cells ranging from 2x1 (H to 2x101 cells. BM reconstitution by the CD4+ fraction of CD34++ cells was more frequent lhan by Ihe CD4" fraction when low numbers of cells were injected. Ai Ihe lowest dose of cells tested, only CD4+ cells gave rise to multilineage BM reconstitution in 3 of 6 SCID-hu mice 125 days after injection. These functional dala strongly suggest that HSC are enriched among CD4+ CD34++ fetal liver cells. This hypothesis was further supported by the observations that CD4+ CD34++ Lin" fetal liver cells were enriched for CDw90+. CD117+, HLA-DR+. CD7-, CD38-, CD45RA", CD7T, and rhodamine 123dull cells, a phenotypic profile believed to represent fetal HSC Furthermore, all CD4+CD14++ cells also expressed CD 13 and CD33.

Original languageEnglish
Pages (from-to)1029
Number of pages1
JournalExperimental Hematology
Volume24
Issue number9
Publication statusPublished - 1996

ASJC Scopus subject areas

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

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