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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-01-0025.
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Blood, 1 January 2003, Vol. 101, No. 1, pp. 112-118
HEMATOPOIESIS
Reversibility of CD34 expression on human hematopoietic stem
cells that retain the capacity for secondary reconstitution
Mo A. Dao,
Jesusa Arevalo, and
Jan A. Nolta
From the Division of Research Immunology and Bone
Marrow Transplantation, Children's Hospital of Los Angeles, CA.
The cell surface protein CD34 is frequently used as a marker for
positive selection of human hematopoietic stem/progenitor cells in
research and in transplantation. However, populations of reconstituting
human and murine stem cells that lack cell surface CD34 protein have
been identified. In the current studies, we demonstrate that CD34
expression is reversible on human hematopoietic stem/progenitor cells.
We identified and functionally characterized a population of human
CD45+/CD34 cells that was recovered from the
bone marrow of immunodeficient beige/nude/xid (bnx) mice 8 to 12 months after transplantation of highly purified human bone
marrow-derived CD34+/CD38 stem/progenitor
cells. The human CD45+ cells were devoid of CD34 protein
and mRNA when isolated from the mice. However, significantly higher
numbers of human colony-forming units and long-term culture-initiating
cells per engrafted human CD45+ cell were recovered from
the marrow of bnx mice than from the marrow of human stem
cell-engrafted nonobese diabetic/severe combined immunodeficient mice,
where 24% of the human graft maintained CD34 expression. In addition
to their capacity for extensive in vitro generative capacity, the human
CD45+/CD34 cells recovered from the
bnx bone marrow were determined to have secondary
reconstitution capacity and to produce CD34+ progeny
following retransplantation. These studies demonstrate that the human
CD34+ population can act as a reservoir for generation of
CD34 cells. In the current studies we demonstrate that
human CD34+/CD38 cells can generate
CD45+/CD34 progeny in a long-term xenograft
model and that those CD45+/CD34 cells can
regenerate CD34+ progeny following secondary
transplantation. Therefore, expression of CD34 can be reversible on
reconstituting human hematopoietic stem cells.
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