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Extensive amplification and self-renewal of human primitive hematopoietic
stem cells from cord blood
W Piacibello, F Sanavio, L Garetto, A Severino, D Bergandi, J Ferrario, F Fagioli, M Berger and M Aglietta
Department of Biomedical Sciences, Torino Medical School, University of
Torino, Italy.
The use of umbilical cord blood as a source of marrow repopulating cells
for the treatment of pediatric malignancies has been established. Given the
general availability, the ease of procurement, and progenitor content, cord
blood is an attractive alternative to bone marrow or growth factor
mobilized peripheral blood cells as a source of transplantable
hematopoietic tissue. However, there is a major potential limitation to the
widespread use of cord blood as a source of hematopoietic stem cells for
marrow replacement and gene therapy. There may be enough hematopoietic stem
cells to reconstitute children, but the ability to engraft an adult might
require ex vivo manipulations. We describe an in vitro system in which the
growth of cord blood CD34+ cells is sustained and greatly expanded for more
than 6 months by the simple combination of two hematopoietic growth
factors. Progenitors and cells belonging to all hematopoietic lineages are
continuously and increasingly generated (the number of colony-forming
unit-granulocyte- macrophage [CFU-GM] present at the end of 6 months of
culture are well over 2,000,000-fold the CFU-GM present at the beginning of
the culture). Very primitive hematopoietic progenitors, including long-term
culture-initiating cells (LTC-ICs) and blast cell colony-forming units, are
also greatly expanded (after 20 weeks of liquid culture, LTC-IC number is
over 200,000-fold the initial number). The extremely prolonged maintenance
and the massive expansion of these progenitors, which share many
similarities with murine long-term repopulating cells, suggest that
extensive renewal and little differentiation take place. This system might
prove useful in diverse clinical settings involving treatment of grown-up
children and adults with transplantation of normal or genetically
manipulated hematopoietic stem cells.
Volume 89,
Issue 8,
pp. 2644-2653,
04/15/1997
Copyright © 1997 by The American Society of Hematology
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