Efficiency of transgenic T cell generation from gene-marked cultured human CD34+ cord blood cells is determined by their maturity and the cytokines present in the culture medium

Verhasselt, Bruno; Naessens, Evelien; Smedt, Magda De; Plum, Jean

doi:10.1038/sj.gt.3301176

Cited by 2 publications

(1 citation statement)

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“…Thus, the higher TREC levels and better preserved thymic architecture in animals transplanted with the cultured‐transduced CD34 + cells may result from the specific characteristics of the graft. In vitro treatment of CD34 + PBPCs with a cytokine cocktail similar to that applied in this study promoted the development of lymphoid progenitor cells that repopulate the thymus [26, 27]. The culture conditions we used during transduction of the CD34 + PBPCs included fibronectin support and media supplemented with SCF, Flt3 ligand, and MDGF.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Culture During Retroviral Transduction Improves Thymic Repopulation and Output After Total Body Irradiation and Autologous Peripheral Blood Progenitor Cell Transplantation in Rhesus Macaques

et al. 2006

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Immunodeficiency after peripheral blood progenitor cell (PBPC) transplantation may be influenced by graft composition, underlying disease, and/or pre-treatment. These factors are difficult to study independently in humans. Ex vivo culture and genetic manipulation of PBPC grafts may also affect immune reconstitution, with relevance to gene therapy applications. We directly compared the effects of three clinically relevant autologous graft compositions on immune reconstitution after myeloblative total body irradiation in rhesus macaques, the first time these studies have been performed in a large animal model with direct clinical relevance. Animals received CD34؉ cell dose-matched grafts of either peripheral blood mononuclear cells, purified CD34 ؉ cells may therefore repopulate the thymus more efficiently and promote a higher output of naïve T-cells. These results have implications for the design of gene therapy trials, as well as for the use of expanded PBPCs for improved T-cell immune reconstitution after transplantation. STEM CELLS 2006;24:1539 -1548

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Section: Discussionmentioning

confidence: 99%