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. 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 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.
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 tripeptideDiprotin 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 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: A Wahlers; M Schwieger; Z Li; D Meier-Tackmann; C Lindemann; H G Eckert; D von Laer; C Baum Journal: Gene Ther Date: 2001-03 Impact factor: 5.250
Authors: K E Pollok; J C van Der Loo; R J Cooper; J R Hartwell; K R Miles; R Breese; E P Williams; A Montel; R Seshadri; H Hanenberg; D A Williams Journal: Hum Gene Ther Date: 2001-11-20 Impact factor: 5.695
Authors: M Cavazzana-Calvo; S Hacein-Bey; G de Saint Basile; F Gross; E Yvon; P Nusbaum; F Selz; C Hue; S Certain; J L Casanova; P Bousso; F L Deist; A Fischer Journal: Science Date: 2000-04-28 Impact factor: 47.728
Authors: O Kollet; A Spiegel; A Peled; I Petit; T Byk; R Hershkoviz; E Guetta; G Barkai; A Nagler; T Lapidot Journal: Blood Date: 2001-05-15 Impact factor: 22.113
Authors: Hal E Broxmeyer; Jonathan Hoggatt; Heather A O'Leary; Charlie Mantel; Brahmananda R Chitteti; Scott Cooper; Steven Messina-Graham; Giao Hangoc; Sherif Farag; Sara L Rohrabaugh; Xuan Ou; Jennifer Speth; Louis M Pelus; Edward F Srour; Timothy B Campbell Journal: Nat Med Date: 2012-11-18 Impact factor: 53.440