title: Enhanced homing and engraftment of fresh but not ex vivo cultured murine marrow cells in submyeloablated hosts following CD26 inhibition by Diprotin A.
abstract: OBJECTIVE
  We recently reported that murine marrow cultured ex vivo for gamma-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.
  
  
  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 gamma-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 gamma-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 gamma-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.
authors.affiliation: Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202-5225,USA.
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Wyss
authors.forename: Abigail F W
authors.initials: AF
authors.lastname: Donnelly
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Sinn
authors.forename: Karen E
authors.initials: KE
authors.lastname: Pollok
authors.forename: W Scott
authors.initials: WS
authors.lastname: Goebel
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D002478:Cells, Cultured; D054873:Dipeptidyl-Peptidase IV Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D019653:Myeloablative Agonists / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D019653:Myeloablative Agonists; D009842:Oligopeptides; D016201:Receptors, Lymphocyte Homing; C041445:diprotin A