重组人Delta-like-1胞外区促进细胞因子对脐带血造血祖细胞的扩增

目的：Notch信号通路对造血干／祖细胞的增殖分化具有重要调控作用。Delta-like-1(Dll-1)是Notch的配体之一，本研究观察了重组人Dll-1胞外区(hDll-1^ext)对细胞因子扩增脐带血造血祖细胞的促进作用。方法：RT-PCR用于检测Notch-1及其配体在脐带血细胞上的表达情况。利用免疫磁性分离(MACS)的方法分离人脐带血CD34 细胞。在无血清培养体系中，hDll-1^ext分别和不同的细胞因子组合联合培养CD34^ 细胞，通过集落形成实验检测hDLl-1^ext对造血祖细胞的扩增作用。结果：RT-PCR方法检测到脐带血单个核细胞表达Notch-1和它的配体Dll-1,Jagged-1，表明在生理条件下，脐血细胞的增殖分化可能受到Notch信号的调控。hDll-1^ext“能促进细胞因子组合对脐带血HPP-CFC的扩增，其中hDll-1^ext和SCF，IL-3，IL-6联合的扩增作用最强，无血清培养8，12d后，HPP-CFC分别增加为培养前的9．7和43倍。结论：重组hDll-1^ext能促进细胞因子对脐带血原始造血祖细胞的扩增作用。

Recombinant extracellular domain of human Delta-like-1 enhances cytokine-induced expansion of cord blood progenitors

Objective: Notch signaling plays important roles in the regulation of proliferation and differentiation of hematopoietic stem/progenitor cells. Delta-like-1(Dll-1) is one of Notch ligands. The effect of recombinant extracellular domain of human Dll-1(hDll-1 ext) on the expansion of cord blood progenitors objective of the present study was to investigate. Methods: RT-PCR was used to examine the expression of Notch-1 and its ligands on cord blood cells. Human umbilical cord blood CD34 + cells were isolated by MACS system and were cultured in serum-free medium containing hDll-1 ext and different combination of cytokines. The effect of hDll-1 ext on the expansion of progenitor cells was then evaluated by generation of CFU-Cs in this system. Results: RT-PCR showed that cord blood-derived mononuclear cells expressed Notch-1,Dll-1 and Jagged-1, suggesting that Notch signals might regulate proliferation and differentiation of cord blood cells in physiological condition. hDll-1 ext enhanced cytokine-induced expansion of cord blood HPP-CFCs. In the presence of hDll-1 ext, HPP-CFCs expanded 9.7 or 43 times after culture with SCF-IL3-IL6 for 8 or 12 days, respectively. Conclusion: The results indicate that the recombinant hDll-1 ext enhances the expansion of primitive hematopoietic progenitors in cord blood.