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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1012-1018
HEMATOPOIESIS
An in vitro model of hematopoietic stem cell homing
demonstrates rapid homing and maintenance of engraftable
stem cells
Angela E. Frimberger,
Allen
I. Stering, and
Peter J. Quesenberry
From The University of Massachusetts Cancer Center,
Worcester.
Hematopoietic stem cell (HSC) homing is believed to rely heavily on
adhesion interactions between stem cells and stroma. An in vitro assay
was developed for adhesion of engraftable HSCs in bone marrow
suspensions to pre-established Dexter-type long-term bone marrow
culture stromal layers. The cell numbers in the adherent layer and
supernatant were examined, along with the engraftment capability of
adherent layer cells to indicate the number of HSCs that homed to in
vitro stroma. The cell number in the supernatant declined over the
24-hour period. The number of test cells adhering to the stromal layer
increased during the first hour and then fell at 6 and 24 hours. The
number of test HSCs adhering to the stromal layer was substantial at 20 minutes, increased during the first hour, and then remained constant at
1, 6, and 24 hours of adhesion. These data indicate that adhesion of
engraftable HSCs occurs quickly and increases during the first hour of
contact with pre-established stroma, that adhesion plateaus within 1 hour of contact, and that HSCs maintain their engraftment capability for at least 24 hours of stromal adhesion. Long-term engraftment from
test cells at more than 1 hour of adhesion represents 70.7% of the
predicted engraftment from equivalent numbers of unmanipulated marrow
cells, indicating that 2 of 3 test engraftable HSCs adhered. These
findings demonstrate the usefulness of this model system for studying
stem-stromal adhesion, allowing further dissection of the mechanism of
HSC homing and exploration of possible manipulations of the process.
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