Immature Human Cord Blood Progenitors Engraft and Proliferate to High Levels in Severe Combined Immunodeficient Mice

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 don...

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Bibliographic Details
Published in:Blood 1994-05, Vol.83 (9), p.2489-2497
Main Authors: Vormoor, Josef, Lapidot, Tsvee, Pflumio, Françoise, Risdon, Grant, Patterson, Bruce, Broxmeyer, Hal E., Dick, John E.
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Antigens, CD - analysis
Biological and medical sciences
Bone marrow, stem cells transplantation. Graft versus host reaction
Cell Division
Colony-Forming Units Assay
DNA - analysis
Fetal Blood - cytology
Flow Cytometry
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Hematopoiesis
Hematopoietic Cell Growth Factors - pharmacology
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - immunology
Humans
Immunophenotyping
Medical sciences
Mice
Mice, SCID
Recombinant Fusion Proteins - pharmacology
Stem Cell Factor
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V83.9.2489.2489