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Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4612-4621
Adhesion to Fibronectin Maintains Regenerative Capacity During Ex
Vivo Culture and Transduction of Human Hematopoietic Stem and
Progenitor Cells
M.A. Dao,
K. Hashino,
I. Kato, and
J.A. Nolta
From the Division of Research Immunology/Bone Marrow Transplantation,
Childrens Hospital Los Angeles, and the Department of Pediatrics,
University of Southern California School of Medicine, Los Angeles, CA;
and the Biotechnology Research Laboratories, Takara Shuzo Co, Ltd,
Otsu, Japan.
Recent reports have indicated that there is poor engraftment from
hematopoietic stem cells (HSC) that have traversed cell cycle ex vivo.
However, inducing cells to cycle in culture is critical to the fields
of ex vivo stem cell expansion and retroviral-mediated gene therapy.
Through the use of a xenograft model, the current data shows that human
hematopoietic stem and progenitor cells can traverse M phase ex vivo,
integrate retroviral vectors, engraft, and sustain long-term
hematopoiesis only if they have had the opportunity to engage their
integrin receptors to fibronectin during the culture period. If
cultured in suspension under the same conditions, transduction is
undetectable and the long-term multilineage regenerative capacity of
the primitive cells is severely diminished.
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