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Blood, 1 September 2000, Vol. 96, No. 5, pp. 1740-1747
HEMATOPOIESIS
Identification of novel circulating human embryonic blood
stem cells
Lisa Gallacher,
Barbara Murdoch,
Dongmei Wu,
Francis Karanu,
Fraser Fellows, and
Mickie Bhatia
From the John P. Robarts Research Institute,
Developmental Stem Cell Biology, London, Ontario, Canada; and
Department of Microbiology and Immunology and Department of Pediatrics,
Fetal Medicine Division, University of Western Ontario, London Health
Sciences, London, Ontario, Canada.
Using murine models, primitive hematopoietic cells capable of
repopulation have been shown to reside in various anatomic locations, including the aortic gonad mesonephros, fetal liver, and bone marrow.
These sites are thought to be seeded by stem cells migrating through
fetal circulation and would serve as ideal targets for in utero
cellular therapy. In humans, however, it is unknown whether similar
stem cells exist. Here, we identify circulating hematopoeitic cells
present during human in utero development that are capable of
multilineage repopulation in immunodeficient NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice. Using limiting dilution
analysis, the frequency of these fetal stem cells was found to be 1 in
3.2 × 105, illustrating a 3- and 22-fold enrichment
compared with full-term human cord blood and circulating adult
mobilized-peripheral blood, respectively. Comparison of in vivo
differentiation and proliferative capacity demonstrated that
circulating fetal stem cells are intrinsically distinct from
hematopoietic stem cells found later in human development and those
derived from the fetal liver or fetal bone marrow compartment at
equivalent gestation. Taken together, these studies demonstrate the
existence of unique circulating stem cells in early human embryonic
development that provide a novel and previously unexplored source of
pluripotent stem cell targets for cellular and gene-based fetal therapies.
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