Non-fucosylated CB CD34⁺ cells represent a good target for enforced fucosylation to improve engraftment following cord blood transplantation

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• 作者：Simon N. Robinson¹ ; ^{simon-robinson@sbcglobal.net} ; Michael W. Thomas¹ ; Paul J. Simmons² ; Junjun Lu¹ ; Hong Yang¹ ; Jeannie A. Javni² ; Elizabeth J. Shpall¹ ; Patrick A. Zweidler-Mckay³
• 关键词：cord blood (CB) ; engraftment ; E-selectin ; fucosylation ; hematopoietic stem and progenitor cell (HSPC)
• 刊名：Cytotherapy
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：19
• 期：2
• 页码：285-292
• 全文大小：959 K
• 卷排序：19

文摘

Despite ethnic diversity and ready availability of cryopreserved, human leukocyte antigen–typed cord blood (CB), delayed engraftment remains a significant hurdle to successful CB transplantation. Suboptimal homing of CB hematopoietic stem and progenitor cells (HSPCs) to the hematopoietic microenvironment (HM) is thought to be responsible and due to low levels of HSPC fucosylation. Fucosylation (decoration with sialyl-LewisX) may improve HSPC homing to HM by increasing the strength of HSPC/E-selectin interactions, where E-selectin is constitutively expressed by HM microvasculature. Enforced fucosylation of CB HSPCs using fucosyltransferases, increases the rate and magnitude of engraftment in xenogeneic transplant models. However, it is unclear whether endogenously fucosylated and non-fucosylated CB HSPC are qualitatively identical or whether endogenous fucosylation marks a qualitative difference between CB HSPC. If qualitatively identical, non-fucosylated CB HSPCs represent a good target for enforced fucosylation with improved engraftment conferred on an increased number of otherwise qualitatively identical HSPC. If qualitatively different, then conferring engraftment upon a majority, possibly lower “quality,” non-fucosylated HSPCs by enforced fucosylation might inadvertently compromise engraftment.MethodsFunctional (xenogeneic engraftment, colony-forming unit and selectin-binding assays) and phenotypic analyses of fluorescence-activated cell sorting–isolated, endogenously fucosylated and non-fucosylated CB CD34+ cells were performed.ResultsEndogenous fucosylation of CB HSPCs exists as a continuum. Endogenously fucosylated HSPCs engrafted more efficiently in a xenogeneic transplantation model than non-fucosylated HSPCs. Outside of the differences in endogenous fucosylation, no other qualitative (functional and/or phenotypic) differences were identified.DiscussionThe majority of endogenously non-fucosylated CB HSPCs represent a good target for enforced fucosylation with the goal of improving engraftment following CB transplantation.