鉴于人的胚胎干细胞在再生医学、组织工程学和药物研发等领域有极高的应用价值,科学家尝试通过各种途径获得胚胎干细胞样的多能干细胞。其中Yamanaka等率先在体外通过病毒载体诱导的方式实现体细胞重新编程,由此得到诱导性多能干细胞。多种无遗传修饰的诱导方式正在尝试和改进中,例如用小分子化合物来代替外源基因进行重编程引起了很大的兴趣。用基于细胞水平的表型筛选法和信号通路筛选法,已筛选出特异小分子或天然产物,也可以特异地将成熟细胞去分化为干细胞,有望运用于组织修复和再生。而利用重组蛋白在体外将体细胞诱导为干细胞,也获得了初步成功。由诱导性多能干细胞在体外诱导分化出的细胞在治疗相应疾病方面展示出一定疗效。不同类型的干细胞向体细胞的定向分化策略都是基于目前对发育生物学的认识,这些研究揭示了一些共同的可能线索。
Scientists have taken various methods to acquire embryonic stem cell-like pluripotent stem cells, since human stem cells have extremely high application value in regeneration medicine, tissue engineering, and drug development. Yamanaka has realized reprogramming of somatic cells through virus vector induction in vitro at first, therefore produced induced pluripotent stem cells (iPS). Non-genetic modifications are being tested; for example, replacement of introduction of exogenous genes by application of small molecule chemicals has drawn huge interests. Cell-level phenotype selection and signal transduction selection have already picked out specific small molecule chemicals or natural products, which can induce mature somatic cells into stem cells that can be applied to tissue repair and regeneration. It is also successful to induce somatic cells into stem cells by recombinant proteins in vitro. On the other side, somatic cells induced from iPS cells in vitro are proved to have therapeutic effects in relative diseases. Direct differentiation strategies turning different type of stem cells into somatic cells are based on current recognition of development biology, and these studies indicate some common clues.