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Title: Ancillary cell help in haematopoietic cord blood engraftment
Author: Escobedo Cousin, M. H.
ISNI:       0000 0004 5363 9342
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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Cord blood (CB) has served as a source of haematopoietic stem cells (HSC) to treat haematological diseases for the last two decades. Low incidence and severity of graft-versus-host disease, and a robust graft-versus-leukaemia effect are some of CB advantages as a source for HSC. However, its main disadvantages are a limited number of HSC per unit and delayed immune reconstitution and infections after CB transplantation (CBT). In order to improve engraftment and immune reconstitution after CBT different approaches have been explored like HSC expansion, double CB transplantation, CBT plus third party donor HSC or intra-bone infusion. It seems as if the interaction of cord blood stem cells (CB SC) with other cells is required for CB SC to engraft. On this basis, the effect of accessory cells, particularly natural killer (NK) cells, on CB SC engraftment was analysed. It was observed that NK cell co-infusion with CB SC led to higher levels of engraftment in NSG mice. This in parallel with a higher level of expression of CXCR4 receptor, a higher migration index, a higher number of colony forming units (CFU) after long-term culture initiating cells assay (LTC-IC) and a trend to a higher number of CFU when CB SC were co-cultured with activated NK cells (aNK). The effect observed on CBSC clonogenic capacity was maintained even after treatment with pertussis toxin (PTX), which blocks G-protein coupled receptors signalling, such as CXCR4. The results presented in this work offer the basis for an alternative approach that could help to improve CBT.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available