Engraftment and retroviral marking of CD34+ and CD34+ CD38- human hematopoietic progenitors assessed in immune-deficient mice

Mo A. Dao, Ami J. Shah, Gay M. Crooks, Jan Nolta

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Retroviral-mediated transduction of human hematopoietic stem cells to provide a lifelong supply of corrected progeny remains the most daunting challenge to the success of human gene therapy. The paucity of assays to examine transduction of pluripotent human stem cella hampers progress toward this goal. By using the beige/nude/xid (bnx)/hu immune-deficient mouse xenograft system, we compared the transduction and engraftment of human CD34+ progenitors with that of a more primitive and quiescent subpopulation, the CD34+CD38- cells. Comparable extents of human engraftment and lineage development were obtained from 5 x 105 CD34+ cells and 2,00.0 CD34+CD38- cells. Retroviral marking of long-lived progenitors from the CD34+ populations was readily accomplished, but CD34+CD38- cells capable of reconstituting bnx mice were resistant to transduction. Extending the duration of transduction from 3 to 7 days resulted in low levels of transduction of CD34+CD38- cells. Flt3 ligand was required during the 7- day ex vivo culture to maintain the ability of the cells to sustain long- term engraftment and hematopoiesis in the mice.

Original languageEnglish (US)
Pages (from-to)1243-1255
Number of pages13
JournalBlood
Volume91
Issue number4
StatePublished - Feb 15 1998
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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