5 肝干细胞的分化机理
肝干细胞的分化是一个复杂的过程，肝干细胞是维持自我复制还是分化为成熟的功能细胞依赖于微环境、细胞生长因子等多种因素的相互作用与平衡。具体来说，肝干细胞分化与增殖的调控因素主要有：（1）时钟，它通过改变细胞周期促进因子或抑制因子的水平，决定干细胞的分裂次数。如Cul1蛋白是一种细胞周期促进因子，它与细胞周期蛋白G1的破坏有关。p27是一种抑制因子，它促进干细胞分化并抑制其增殖。（2）微环境，有学者[15]将肝卵圆形细胞移植到大鼠肝组织时，卵圆形细胞分化成为肝实质细胞，卵圆形细胞经皮下移植时常常形成易转移和分化程度低的肿瘤，其原因可能是皮下基质抑制卵圆形细胞分化为肝细胞，因而促进瘤生物的形成。（3）生长因子和细胞外基质，它们在肝干细胞分化为肝实质细胞的过程中有重要作用。有学者[16]报道，肝细胞生长因子(HGF)可诱导白蛋白阴性的肝干细胞转变为白蛋白阳性的肝祖细胞。
6 小结与展望
综上所述，有关肝干细胞活化、分离培养、筛选及鉴定等尚未成熟，肝干细胞的研究有待进一步发展和完善，可以肯定的是其分子机制的研究将是未来研究的主要内容，而肝干细胞与肿瘤发生的关系以及肿瘤干细胞相关治疗将是研究的一个重要方面。
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