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Sustained, retransplantable, multilineage engraftment of highly purified
adult human bone marrow stem cells in vivo
CI Civin, G Almeida-Porada, MJ Lee, J Olweus, LW Terstappen and ED Zanjani
Department of Oncology, Johns Hopkins University School of Medicine,
Baltimore, MD, USA.
Data from many laboratory and clinical investigations indicate that CD34+
cells comprise approximately 1% of human bone marrow (BM) mononuclear
cells, including the progenitor cells of all the lymphohematopoietic
lineages and lymphohematopoietic stem cells (stem cells). Because stem
cells are an important but rare cell type in the CD34+ cell population,
investigators have subdivided the CD34+ cell population to further enrich
stem cells. The CD34+/CD38- cell subset comprises less than 10% of human
CD34+ adult BM cells (equivalent to < 0.1% of marrow mononuclear cells),
lacks lineage (lin) antigens, contains cells with in vitro replating
capacity, and is predicted to be highly enriched for stem cells. The
present investigation tested whether the CD34+/CD38- subset of adult human
marrow generates human hematopoiesis after transfer to preimmune fetal
sheep. CD34+/ CD38- cells purified from marrow using immunomagnetic
microspheres or fluorescence-activated cell sorting generated easily
detectable, long- term, multilineage human hematopoiesis in the human-fetal
sheep in vivo model. In contrast, transfer of CD34+/CD38+ cells to
preimmune fetal sheep generated only short-term human hematopoiesis,
possibly suggesting that the CD34+/CD38+ cell population contains
relatively early multipotent hematopoletic progenitor cells, but not stem
cells. This work extends the prior in vitro evidence that the earliest
cells in fetal and adult human marrow lack CD38 expression. In summary, the
CD34+/ CD38- cell population has a high capacity for long-term multilineage
hematopoietic engraftment, suggesting the presence of stem cells in this
minor adult human marrow cell subset.
Volume 88,
Issue 11,
pp. 4102-4109,
12/01/1996
Copyright © 1996 by The American Society of Hematology
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