Dataset Information

Fucosylation with fucosyltransferase VI or fucosyltransferase VII improves cord blood engraftment.

ABSTRACT: 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.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.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.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.

SUBMITTER: Robinson SN

PROVIDER: S-EPMC3883688 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fucosylation with fucosyltransferase VI or fucosyltransferase VII improves cord blood engraftment.

Robinson Simon N SN Thomas Michael W MW Simmons Paul J PJ Lu Junjun J Yang Hong H Parmar Simrit S Liu Xiaoying X Shah Nina N Martín-Antonio Beatriz B Bollard Catherine C Dotti Gianpietro G Savoldo Barbara B Cooper Laurence J LJ Najjar Amer A Rezvani Katayoun K Kaur Indreshpaul I McNiece Ian K IK Champlin Richard E RE Miller Leonard P LP Zweidler-McKay Patrick A PA Shpall Elizabeth J EJ

Cytotherapy 20131001 1

<h4>Background aims</h4>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 ...[more]

PMID: 24094497

Similar Datasets

Project description:BackgroundPoor engraftment due to low cell doses restricts the usefulness of umbilical-cord-blood transplantation. We hypothesized that engraftment would be improved by transplanting cord blood that was expanded ex vivo with mesenchymal stromal cells.MethodsWe studied engraftment results in 31 adults with hematologic cancers who received transplants of 2 cord-blood units, 1 of which contained cord blood that was expanded ex vivo in cocultures with allogeneic mesenchymal stromal cells. The results in these patients were compared with those in 80 historical controls who received 2 units of unmanipulated cord blood.ResultsCoculture with mesenchymal stromal cells led to an expansion of total nucleated cells by a median factor of 12.2 and of CD34+ cells by a median factor of 30.1. With transplantation of 1 unit each of expanded and unmanipulated cord blood, patients received a median of 8.34×10(7) total nucleated cells per kilogram of body weight and 1.81×10(6) CD34+ cells per kilogram--doses higher than in our previous transplantations of 2 units of unmanipulated cord blood. In patients in whom engraftment occurred, the median time to neutrophil engraftment was 15 days in the recipients of expanded cord blood, as compared with 24 days in controls who received unmanipulated cord blood only (P<0.001); the median time to platelet engraftment was 42 days and 49 days, respectively (P=0.03). On day 26, the cumulative incidence of neutrophil engraftment was 88% with expansion versus 53% without expansion (P<0.001); on day 60, the cumulative incidence of platelet engraftment was 71% and 31%, respectively (P<0.001).ConclusionsTransplantation of cord-blood cells expanded with mesenchymal stromal cells appeared to be safe and effective. Expanded cord blood in combination with unmanipulated cord blood significantly improved engraftment, as compared with unmanipulated cord blood only. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00498316.).

Dataset Information

Fucosylation with fucosyltransferase VI or fucosyltransferase VII improves cord blood engraftment.

Publications

Fucosylation with fucosyltransferase VI or fucosyltransferase VII improves cord blood engraftment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets