Engraftment of ex vivo expanded and cycling human cord blood hematopoietic progenitor cells in SCID mice

S. E. Spence, J. R. Keller, F. W. Rescetti, C. S. McCauslin, J. M. Gooya, S. Funakoshi, D. L. Longo, William J Murphy

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The ability of human hematopoietic cells to engraft SCID mice provides a useful model in which to study the efficiency of retrovital gene transfer and expression in primitive stem cells. In this regard, it is necessary to determine whether SCID mice can be engrafted by cycling human hematopoietic progenitor cells. Human cord blood cells from 12 different donors were cultured in vitro for 6 days with interleukin-3 and stem cell factor. Phenotypic analysis indicated that hematopoietic cells were induced to cycle and the number of progenitors was expanded, thus making them targets for retrovital gene transfer. The cells were then transferred to SCID mice. Human hematopoietic progenitor cell engraftment was assessed up to 7 weeks later by growth of human progenitor cells in soft agar. After in vitro culture under conditions used for retroviral gene transfer, human cord blood hematopoietic cells engrafted the bone marrow and spleen of SCID mice. Interestingly, cultured cord blood cells engrafted after intraperitoneal but not after intravenous injection. Furthermore, engraftment of cord blood cells was observed in mice receiving no irradiation before transfer of the human cells, suggesting that competition for space in the marrow is not a limiting factor when these cells have been cultured. Administration of human cytokines after transfer of human cord blood cells to SCID mice was also not required for engraftment. Thus, engraftment of SCID mice with human hematopoietic cells cultured under conditions suitable for gene transfer may provide an in vivo assay for gene transfer to early human hematopoietic progenitor cells.

Original languageEnglish (US)
Pages (from-to)507-514
Number of pages8
JournalExperimental Hematology
Volume26
Issue number6
StatePublished - 1998
Externally publishedYes

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Keywords

  • Gene therapy
  • Hematopoiesis
  • In vivo
  • Severe combined immune deficiency
  • Xenograft

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Spence, S. E., Keller, J. R., Rescetti, F. W., McCauslin, C. S., Gooya, J. M., Funakoshi, S., Longo, D. L., & Murphy, W. J. (1998). Engraftment of ex vivo expanded and cycling human cord blood hematopoietic progenitor cells in SCID mice. Experimental Hematology, 26(6), 507-514.