Enhanced homing and engraftment of fresh but not ex vivo cultured murine marrow cells in submyeloablated hosts following CD26 inhibition by Diprotin A.
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.
Wyss
Brandon K
BK
Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202-5225,USA.
Donnelly
Abigail F W
AF
Zhou
Dan
D
Sinn
Anthony L
AL
Pollok
Karen E
KE
Goebel
W Scott
WS
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
D054873:Dipeptidyl-Peptidase IV Inhibitors; D019653:Myeloablative Agonists; D009842:Oligopeptides; D016201:Receptors, Lymphocyte Homing; C041445:diprotin A