Fucosylation with fucosyltransferase VI or fucosyltransferase VII improves cord blood engraftment

• Published in: Cytotherapy (Oxford, England) England), 2014, Vol.16 (1), p.84-89
• Main Authors: Robinson, Simon N, Thomas, Michael W, Simmons, Paul J, Lu, Junjun, Yang, Hong, Parmar, Simrit, Liu, Xiaoying, Shah, Nina, Martín-Antonio, Beatriz, Bollard, Catherine, Dotti, Gianpietro, Savoldo, Barbara, Cooper, Laurence J, Najjar, Amer, Rezvani, Katayoun, Kaur, Indreshpaul, McNiece, Ian K, Champlin, Richard E, Miller, Leonard P, Zweidler-McKay, Patrick A, Shpall, Elizabeth J
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; cord blood hematopoietic stem and progenitor cells; Disease Models, Animal; Fetal Blood - cytology; Fetal Blood - drug effects; Fetal Blood - transplantation; FTVI; FTVII; fucosylation; Fucosyltransferases - administration & dosage; Graft vs Host Disease - pathology; Graft vs Host Disease - therapy; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cells - drug effects; Humans; improved engraftment; Mice; Other
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2013.07.003

Abstract Background aims Advantages associated with the use of cord blood (CB) transplantation include the availability of cryopreserved units, ethnic diversity and lower incidence of graft-versus-host disease compared with bone marrow or mobilized peripheral blood. However, poor engraftment remains a major obstacle. We and others have found that ex vivo fucosylation can enhance engraftment in murine models, and now ex vivo treatment of CB with fucosyltransferase (FT) VI before transplantation is under clinical evaluation ( NCT01471067 ). However, FTVII appears to be more relevant to hematopoietic cells and may alter acceptor substrate diversity. The present study compared the ability of FTVI and FTVII to improve the rapidity, magnitude, multi-lineage and multi-tissue engraftment of human CB hematopoietic stem and progenitor cells (HSPCs) in vivo. Methods CD34-selected CB HSPCs were treated with recombinant FTVI, FTVII or mock control and then injected into immunodeficient mice and monitored for multi-lineage and multi-tissue engraftment. Results Both FTVI and FTVII fucosylated CB CD34+ cells in vitro , and both led to enhanced rates and magnitudes of engraftment compared with untreated CB CD34+ cells in vivo . Engraftment after treatment with either FT was robust at multiple time points and in multiple tissues with similar multi-lineage potential. In contrast, only FTVII was able to fucosylate T and B lymphocytes. Conclusions Although FTVI and FTVII were found to be similarly able to fucosylate and enhance the engraftment of CB CD34+ cells, differences in their ability to fucosylate lymphocytes may modulate graft-versus-tumor or graft-versus-host effects and may allow further optimization of CB transplantation.