| 摘要 |
This invention demonstrates that FC function via TNF-alpha to affect function of HSC. FC from TNF-alpha deficient mice are impaired in facilitating HSC engraftment in both the syngeneic and allogeneic models. Co-incubation of FC with HSC results in significant increase in TNF-alpha at the mRNA and protein level, and increase in transcript for Bcl-3 in HSC. Furthermore, neutralization of TNF-alpha results in the loss of FC ability to increase HSC clonogenicity and survival, as well as to upregulate Bcl-2 transcript in HSC, demonstrating a critical role for TNF-alpha in FC function. These results offer a mechanism of action for HSC regulation by accessory cells in the bone marrow and confirm the advantage of their co-transplantation with HSC to improve graft efficiency.
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