Enhanced homing and engraftment of fresh but not ex vivo cultured murine marrow cells in submyeloablated hosts following CD26 inhibition by Diprotin A

Brandon K. Wyss, Abigail F.W. Donnelly, Dan Zhou, Anthony L. Sinn, Karen E. Pollok, W. Scott Goebel

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Objective: We recently reported that murine marrow cultured ex vivo for γ-retrovirus transduction engrafts approximately 10-fold less well than fresh marrow upon transplantation into submyeloablated hosts. Here, we evaluated homing efficiency as a potential mechanism for this engraftment disparity, and whether CD26 inhibition with the tripeptide Diprotin A (DipA) would enhance engraftment of ex vivo cultured cells in submyeloablated hosts. Materials and Methods: Homing and engraftment of fresh and ex vivo cultured lineage-negative (lin-) marrow cells in submyeloablated congenic hosts with and without DipA treatment was evaluated. Expression of CXCR4 and CD26 on fresh and cultured lin- marrow cells was compared. Results: Homing of lin- cells cultured for γ-retrovirus transduction was at least threefold less than that of fresh lin- cells 20 hours after transplantation into submyeloablated hosts. DipA treatment of fresh lin- cells resulted in at least twofold increased homing and engraftment in submyeloablated hosts. DipA treatment, however, did not significantly improve homing or engraftment of cells undergoing a 3-day culture protocol for γ-retrovirus transduction in submyeloablated hosts. CXCR4 expression on lin- cells was significantly decreased following 3 days of culture; CXCR4 expression was not significantly altered following overnight culture. Conclusions: Ex vivo culture of lin- cells for γ-retroviral transduction downregulates CXCR4 expression and markedly impairs homing and engraftment of murine lin- marrow in submyeloablated hosts. While inhibition of CD26 activity with DipA increases homing and engraftment of fresh lin- cells, DipA treatment does not improve homing and engraftment of cultured lin- marrow cells in submyeloablated congenic hosts.

Original languageEnglish (US)
Pages (from-to)814-823
Number of pages10
JournalExperimental Hematology
Volume37
Issue number7
DOIs
StatePublished - Jul 1 2009

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ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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