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本帖最后由 tpwang 于 2011-3-9 11:00 编辑 # Y1 `& d; i/ J& ]
8 ]! D" e3 g+ d" Y回复 细胞海洋 的帖子
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这类方法个人认为可命名为“只差一步法”或“最后一步法”。iPS在证明重编程潜能上功不可没，但除了变异风险，更现实的问题是“太麻烦”。所以有人在想是否不要倒回到最原初状态，就可以再回来。直接转分化是一个挑战，另一个思路是沿着经典iPS路子，走半截，或只走最后一步。丁盛年初的文章是“走半截”的方法，即用传统iPS鸡尾酒一过性提升重编程性，然后把细胞放在指向靶细胞的诱导条件下，半直接地转化为靶细胞，而不再经过完全多潜能状态，用的是心肌细胞模型。这个研究则从两方面抄了捷径，一是选择靶细胞的前体细胞，这些细胞相比较胚胎干等多潜能干细胞只缺自我更新一条，然后把这一条在体外（有条件地）“补上”，再放进体内，假定它会完成最后一步，即分化为靶细胞起到治疗作用，用的是神经细胞模型。可称作“最后一步法”，作者称为“条件性诱导自我更新前体细胞”（induced conditional self-renewing progenitor （ICSP） cells“。这篇文章的不同在于它完成了一个从细胞重组到动物实验的基本完整概念证明过程。0 c1 |: | y- t+ p- a8 G
1 M1 E* a" k7 B# F( e8 F总而言之，大家似乎在想办法绕过iPS倒回原始状态过程中的风险和麻烦，寻找高效又安全的捷径。有兴趣的实验室不妨沿着这个原则广开思路，找一些可能的“捷径”和“出发点”，抢先发些概念性的文章还是可能的，估计今年会出一批这类结果。丁盛和这篇都是去年接到今年初发表的。各实验室早在想什么，与发表的结果之间是有时间差的。
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) l/ p: g. F! FIn the field of induced potency and fate reprogramming, it remains unclear what the best starting cell might be and to what extent a cell need be transported back to a more primitive state for translational purposes. Reprogramming a committed cell back to pluripotence to then instruct it toward a particular specialized cell type is demanding and may increase risks of neoplasia and undesired cell types. Precursor/progenitor cells from the organ of therapeutic concern typically lack only one critical attribute—the capacity for sustained self-renewal. We speculated that this could be induced in a regulatable manner such that cells proliferate only in vitro and differentiate in vivo without the need for promoting pluripotence or specifying lineage identity. As proof-of-concept, we generated and tested the efficiency, safety, engraftability, and therapeutic utility of “induced conditional self-renewing progenitor (ICSP) cells” derived from the human central nervous system (CNS); we conditionally induced self-renewal efficiently within neural progenitors solely by introducing v-myc tightly regulated by a tetracycline (Tet)-on gene expression system. Tet in the culture medium activated myc transcription and translation, allowing efficient expansion of homogeneous, clonal, karyotypically normal human CNS precursors ex vivo; in vivo, where Tet was absent, myc was not expressed, and self-renewal was entirely inactivated (as was tumorigenic potential). Cell proliferation ceased, and differentiation into electrophysiologically active neurons and other CNS cell types in vivo ensued upon transplantation into rats, both during development and after adult injury—with functional improvement and without neoplasia, overgrowth, deformation, emergence of non-neural cell types, phenotypic or genomic instability, or need for immunosuppression. This strategy of inducing self-renewal might be applied to progenitors from other organs and may prove to be a safe, effective, efficient, and practical method for optimizing insights gained from the ability to reprogram cells.6 W. N4 B- P- `' m4 ?
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发表于 2011-3-9 10:27
发表于 2011-3-9 10:57
