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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1190-1196
HEMATOPOIESIS
Cultivation of aorta-gonad-mesonephros-derived hematopoietic
stem cells in the fetal liver microenvironment amplifies long-term
repopulating activity and enhances engraftment to the bone
marrow
Masaki Takeuchi,
Takashi Sekiguchi,
Takahiko Hara,
Taisei Kinoshita, and
Atsushi Miyajima
From the Institute of Molecular and Cellular
Biosciences, the University of Tokyo, Japan; and CREST, Core Research
for Evolutional Science and Technology of Japan Science and Technology,
Tokyo, Japan.
During mammalian development, definitive hematopoietic stem cells
(HSCs) arise in the aorta-gonad-mesonephros (AGM) region and colonize
the fetal liver (FL) before hematopoiesis occurs in the bone marrow.
The FL is a unique hematopoietic organ where both HSCs and mature blood
cells are actively generated along with functional maturation of
hepatic cells as a metabolic organ. To characterize HSCs and FL
microenvironments during development, this study establishes a
coculture system composed of AGM-originated HSCs and FL
nonhematopoietic cells. The results demonstrate that FL cells support
significant expansion of lineage-committed hematopoietic cells as well
as immature progenitors. More important, long-term repopulating
activity was amplified from AGM-originated HSCs in this coculture
system. Engraftment of HSCs to the bone marrow was strongly enhanced by
coculture. In addition, AGM HSCs produced significantly more
hematopoietic cells than E14.5 and E18.5 FL HSCs in vitro. These
results suggest that the FL microenvironment not only stimulates
expansion of the hematopoietic system, but also possibly modifies the
characteristics of AGM HSCs. Thus, this coculture system recapitulates
the developmental process of HSCs and the FL microenvironment and
provides a novel means to study the development of hematopoiesis.
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