Reprogramming cells and tissue patterning via bioelectrical pathways: molecular mechanisms and biomedical opportunities.

Reprogramming cells and tissue patterning via bioelectrical pathways: molecular mechanisms and biomedical opportunities.
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DOI:
10.1002/wsbm.1236
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发表时间:
2013-11
影响因子:
7.9
通讯作者:
Levin, Michael
Levin, Michael
中科院分区:
医学3区
文献类型:
--
作者:
Levin, Michael

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再生医学的变革性影响需要的不仅仅是单个细胞的重编程:先天缺陷或损伤的修复策略的进步,肿瘤正常化,以及生物工程器官和组织的构建都需要控制大规模解剖形状的能力。最近的许多工作集中在细胞行为和形态发生的转录和生化调节上。然而,令人兴奋的新数据显示,细胞及其微环境的生物电特性对细胞的分化、增殖和迁移具有深远的影响。在所有细胞中表达的离子通道和泵,不仅仅是可兴奋的神经和肌肉,在不同组织中建立静息电位,并随着重大发育事件而变化。最重要的是,这些内源性跨膜电压电位(Vmem)的时空梯度为大规模解剖提供了指导性的模式线索,为形态发生提供了器官身份、位置信息和模式前模板线索。生物体内生物电梯度分子调控的新遗传和药理学技术揭示了启动复杂器官发生、改变组织特性和触发整个脊椎动物附属物再生的能力。空间信息处理的很大一部分是电的,它协调了单个细胞的程序,以满足宿主生物的解剖需要;这模糊了神经网络的记忆和决策与非神经组织的形态发生之间的界限。破解这种生物电密码的进展将使整个组织和器官的形状合理地重新编程成为可能,从而彻底改变再生医学、发育生物学和合成生物工程。
Transformative impact in regenerative medicine requires more than the reprogramming of individual cells: advances in repair strategies for birth defects or injuries, tumor normalization, and the construction of bioengineered organs and tissues all require the ability to control large-scale anatomical shape. Much recent work has focused on the transcriptional and biochemical regulation of cell behaviour and morphogenesis. However, exciting new data reveal that bioelectrical properties of cells and their microenvironment exert a profound influence on cell differentiation, proliferation, and migration. Ion channels and pumps expressed in all cells, not just excitable nerve and muscle, establish resting potentials that vary across tissues and change with significant developmental events. Most importantly, the spatio-temporal gradients of these endogenous transmembrane voltage potentials (Vmem) serve as instructive patterning cues for large-scale anatomy, providing organ identity, positional information, and prepattern template cues for morphogenesis. New genetic and pharmacological techniques for molecular modulation of bioelectric gradients in vivo have revealed the ability to initiate complex organogenesis, change tissue identity, and trigger regeneration of whole vertebrate appendages. A large segment of the spatial information processing that orchestrates individual cells’ programs towards the anatomical needs of the host organism is electrical; this blurs the line between memory and decision-making in neural networks and morphogenesis in non-neural tissues. Advances in cracking this bioelectric code will enable the rational reprogramming of shape in whole tissues and organs, revolutionizing regenerative medicine, developmental biology, and synthetic bioengineering.
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