Department of Biology, Tufts Center for Regenerative Developmental Biology, Tufts University, Medford, MA, USA.
Wiley Interdiscip Rev Syst Biol Med. 2013 Nov-Dec;5(6):657-76. doi: 10.1002/wsbm.1236. Epub 2013 Jul 29.
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 behavior 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 spatiotemporal 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 toward the anatomical needs of the host organism is electrical; this blurs the line between memory and decision-making in neural networks and morphogenesis in nonneural 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.
在修复先天缺陷或损伤、肿瘤正常化以及构建生物工程器官和组织方面的进展都需要控制大规模的解剖形状的能力。最近的大量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，令人兴奋的新数据揭示了细胞的生物电学特性及其微环境对细胞分化、增殖和迁移有深远的影响。所有细胞都表达的离子通道和泵，不仅仅是可兴奋的神经和肌肉，建立了在组织之间变化且随着重大发育事件而变化的静息电位。最重要的是，这些内源性跨膜电压势（Vmem）的时空梯度作为大规模解剖结构的指导模式线索，为器官身份、位置信息和形态发生的预模式模板线索提供了指导。用于体内生物电梯度的分子调节的新遗传和药理学技术已经揭示了引发复杂器官发生、改变组织身份和触发整个脊椎动物附肢再生的能力。协调单个细胞的程序以满足宿主生物体的解剖需求的空间信息处理的很大一部分是电的；这模糊了神经网络中的记忆和决策以及非神经组织中的形态发生之间的界限。破解这个生物电密码的进展将使我们能够对整个组织和器官的形状进行合理的重新编程，从而彻底改变再生医学、发育生物学和合成生物工程。
