title: Reversible expression of CD34 by adult human bone marrow long-term engrafting hematopoietic stem cells.
abstract: OBJECTIVE
  We previously reported that CD34(-) population of bone marrow (BM) cells from adult humans contains cells capable of engraftment and multilineage differentiation. We also reported on the reversibility of CD34 expression by murine hematopoietic stem cells. Based on long-term observations in primary, secondary, and tertiary sheep recipients, we now present definitive evidence for the long-term engrafting capability of human BM CD34(-) cells, and the reversibility of CD34 expression by human BM hematopoietic stem cells (HSC) in vivo.
  
  
  METHODS
  We used serial transplantations into primary, secondary, and tertiary preimmune fetal sheep recipients to evaluate and compare the long-term engraftment and differentiation of adult human bone marrow-derived CD34(-) and CD34(+) cells in vivo.
  
  
  RESULTS
  In primary hosts CD34(-) or CD34(+) cells produced multilineage human cell activity that persisted for 31 months. To confirm the long-term engrafting characteristics of CD34(-) cells and determine whether CD34 expression on human HSC is reversible, we transplanted human CD34(-) and CD34(+) cells obtained from primary hosts into secondary sheep recipients. Multilineage engraftment occurred in all secondary hosts, and in tertiary hosts transplanted with CD34(-) or CD34(+) cells obtained from BM of secondary recipients.
  
  
  CONCLUSIONS
  These results demonstrate that human BM CD34(-) cells are capable of long-term multilineage engraftment in vivo. The finding that both CD34(-) and CD34(+) cells from primary/secondary groups engraft secondary/tertiary hosts indicates that CD34 expression on human HSC is reversible, a process that does not impair HSC function in vivo.
authors.affiliation: Department of Animal Biotechnology, University of Nevada, Reno, Nev., USA. zanjani@scs.unr.edu
authors.forename: Esmail D
authors.initials: ED
authors.lastname: Zanjani
authors.forename: Graça
authors.initials: G
authors.lastname: Almeida-Porada
authors.forename: Anne G
authors.initials: AG
authors.lastname: Livingston
authors.forename: HaiQun
authors.initials: H
authors.lastname: Zeng
authors.forename: Makio
authors.initials: M
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis*; D001854:Bone Marrow Cells / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D012756:Sheep; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34