In Vitro Differentiation and Expansion of Intrathymic T Cell Progenitors from Human Umbilical Cord Blood-Derived CD34(+) Cells

人脐带血来源的CD34(+)细胞在体外分化和扩增胸腺内T细胞祖细胞

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Abstract

BACKGROUND AND OBJECTIVES: CD4 positive cells play a central role in many lethal diseases, such as AIDS, cancer and autoimmunity diseases. CD4(-) commitment of hematopoietic stem cells involved in T cell lineage, monocyte and dendritic cells development. In this study, we showed that CD4 commitment out of thymus which may happen when hematopoietic cells undergo monocyte, dendritic cells or even earlier T cell progenitor differentiation. METHODS AND RESULTS: after culturing in our medium for more than five weeks, CD4(-)CD34(+) fraction, isolated from human umbilical cord blood, decreased to 1%. However, the fraction expressing CD4 went up to 86.5%. After CD4(+) cells were cultured in methylcellulose-based CFU medium, about 40 colonies/2×10(4) cells could developed. An activation of notch-1 pathway in the freshly isolated CD34(+) cells and up-regulation of PI3K/JNK/c-Myc pathway may provide an explanation for the differentiation and proliferation of CD4(+) cells from CD34(+) hematopoietic stem cells respectively. CONCLUSIONS: ACD4(+) enriched population was obtained after highly purified CD34(+) cells, isolated from human cord blood, underwent long term culture in a feeder layer-free culturing system. Colonigenic ability was maintained in the population of CD4(+) cells. This finding will be a benefit for the studies on the cell therapy for immune dysfunctions.

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