Improved engraftment of human hematopoietic cells in severe combined immunodeficient (SCID) mice carrying human cytokine transgenes

Thomas A. Bock, Donald Orlic, Cynthia E. Dunbar, Hal Broxmeyer, David M. Bodine

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

We have generated immunodeficient scid-/scid (SCID)-transgenic mice expressing the genes for human interleukin-3, granulocyte/macrophage-colony stimulating factor, and stem cell factor. We have compared engraftment and differentiation of human hematopoietic cells in transgenic SCID mice with two strains of nontransgenic SCID mice. Human bone marrow cells carrying the CD34 antigen or human umbilical cord blood were injected into sublethally irradiated recipients. Human DNA was detected by polymerase chain reaction in peripheral blood and bone marrow of 14 of 28 transgenic SCID mice after transplantation, but in only 2 of 15 nontransgenic SCID littermates at a 10- fold lower level. Bone marrow cultures 8 wk after transplantation of cord blood gave rise to human burst-forming unit erythroid, colony-forming unit granulocyte/macrophage, or granulocyte/erythroid/macrophage/megakaryocyte colonies. Engraftment was observed for up to 6 mo in transgenic SCID mice, twice as long as nontransgenic littermates or previous studies in which transplanted SCID mice were given daily injections of growth factors. We conclude that the level and duration of engraftment of human cells in SCID mice can be improved by expression of human cytokine transgenes and that transgenic SCID mice are an efficient model system for the study of human hematopoiesis.

Original languageEnglish
Pages (from-to)2037-2043
Number of pages7
JournalJournal of Experimental Medicine
Volume182
Issue number6
DOIs
StatePublished - Dec 1 1995

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SCID Mice
Transgenes
Cytokines
Transgenic Mice
Fetal Blood
Granulocytes
Transplantation
Bone Marrow
CD34 Antigens
Macrophages
Erythroid Precursor Cells
Stem Cell Factor
Megakaryocytes
Interleukin-3
Hematopoiesis
Granulocyte-Macrophage Colony-Stimulating Factor
Bone Marrow Cells
Intercellular Signaling Peptides and Proteins
Polymerase Chain Reaction
Injections

ASJC Scopus subject areas

  • Immunology

Cite this

Improved engraftment of human hematopoietic cells in severe combined immunodeficient (SCID) mice carrying human cytokine transgenes. / Bock, Thomas A.; Orlic, Donald; Dunbar, Cynthia E.; Broxmeyer, Hal; Bodine, David M.

In: Journal of Experimental Medicine, Vol. 182, No. 6, 01.12.1995, p. 2037-2043.

Research output: Contribution to journalArticle

Bock, Thomas A. ; Orlic, Donald ; Dunbar, Cynthia E. ; Broxmeyer, Hal ; Bodine, David M. / Improved engraftment of human hematopoietic cells in severe combined immunodeficient (SCID) mice carrying human cytokine transgenes. In: Journal of Experimental Medicine. 1995 ; Vol. 182, No. 6. pp. 2037-2043.
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