Rescue of developmental defects by blastocyst stem cell injection: towards elucidation of neomorphic corrective pathways.
Rescue of developmental defects by blastocyst stem cell injection: towards elucidation of neomorphic corrective pathways.
复制标题
通过囊胚干细胞注射挽救发育缺陷：阐明新形态的纠正途径。
DOI：
10.1007/s12265-009-9140-7
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发表时间：
2010
影响因子：
3.4
通讯作者：
Fraidenraich,Diego
中科院分区：
文献类型：
--
作者：
Zhao,Qingshi;Beck,Amanda;Vitale,JosephM;Schneider,JoelS;Terzic,Andre;Fraidenraich,Diego
干细胞为基础的治疗是一个令人兴奋的领域，再生医学的高潜力。为了研究疾病预防，我们将小鼠胚胎干细胞（ESCs）注射到多种小鼠囊胚中，其中大多数具有突变。从这些突变囊胚衍生的小鼠在发育阶段或成年后会发生类似人类的疾病，但囊胚注射ESCs可防止疾病发生。而不是完全重新填充受影响的器官，只有20%的嵌合，ESCs补充了突变小鼠中缺乏的蛋白质水平，并诱导新的或“新形态”信号，帮助规避突变的要求。我们还展示了数据表明，无论宿主囊胚的性质（突变型或野生型）如何，“新形态”机制都是囊胚注射ESCs的结果。因此，胚胎干细胞的囊胚注射不仅可以研究疾病的预防，而且还揭示了新的途径，其激活可能有助于纠正先天性或后天性疾病。
Stem cell-based therapy is an exciting area of high potential for regenerative medicine. To study disease prevention, we inject mouse embryonic stem cells (ESCs) into a variety of mouse blastocysts, most of which harbor mutations. Mice derived from these mutant blastocysts develop human-like diseases, either at developmental stages or in the adult, but blastocyst injection of ESCs prevents disease from occurring. Rather than entirely repopulating the affected organs, with just 20% of chimerism, the ESCs replenish protein levels that are absent in mutant mice, and induce novel or "neomorphic" signals that help circumvent the requirements for the mutations. We also show data indicating that the "neomorphic" mechanisms arise as a result of blastocyst injection of ESCs, regardless of the nature of the host blastocyst (mutant or wild-type). Thus, blastocyst injection of ESCs not only allows the study of disease prevention, but also unveils novel pathways whose activation may aid in the correction of congenital or acquired disease.