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Immature human cord blood progenitors engraft and proliferate to high
levels in severe combined immunodeficient mice
J Vormoor, T Lapidot, F Pflumio, G Risdon, B Patterson, HE Broxmeyer and JE Dick
Department of Genetics, Hospital for Sick Children, Toronto, Ontario,
Canada.
Unseparated or Ficoll-Hypaque (Pharmacia, Piscataway, NJ)--fractionated
human cord blood cells were transplanted into sublethally irradiated severe
combined immunodeficient (SCID) mice. High levels of multilineage
engraftment, including myeloid and lymphoid lineages, were obtained with
80% of the donor samples as assessed by DNA analysis,
fluorescence-activated cell sorting (FACS), and morphology. In contrast to
previous and concurrent studies with adult human bone marrow (BM),
treatment with human cytokines was not required to establish high-level
human cell engraftment, suggesting that neonatal cells either respond
differently to the murine microenvironment or they provide their own
cytokines in a paracrine fashion. Committed and multipotential myelo-
erythroid progenitors were detected using in vitro colony assays and FACS
analysis of the murine BM showed the presence of immature CD34+ cells. In
addition, human hematopoiesis was maintained for at least 14 weeks
providing further evidence that immature hematopoietic precursors had
engrafted the murine BM. This in vivo model for human cord blood- derived
hematopoiesis will be useful to gain new insights into the biology of
neonatal hematopoietic cells and to evaluate their role in gene therapy.
There is growing evidence that there are ontogeny-related changes in
immature human hematopoietic cells, and therefore, the animal models we
have developed for adult and neonatal human hematopoiesis provide useful
tools to evaluate these changes in vivo.
Volume 83,
Issue 9,
pp. 2489-2497,
05/01/1994
Copyright © 1994 by The American Society of Hematology
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