Bryant Susan V, Gardiner David M
University of California Irvine, Irvine, CA, USA.
Int J Dev Biol. 2018;62(6-7-8):363-368. doi: 10.1387/ijdb.170269dg.
The explosive growth of information from genetics and genomics has led to an appreciation of the conservation of gene regulatory networks between organisms, and between development and regeneration. With ever increasing knowledge, it will be possible to intervene therapeutically to regulate these networks, which will lead to new therapies to induce regeneration. The question then becomes how to do this, rather then when to try. Our thesis is that the time is now, and that this feat can be achieved by combining the insights provided by developmental biologists with the technologies being developed by biomaterial engineers, to achieve the goal of engineering regeneration. We thus envision regenerative engineering as the next step toward achieving the goal of human regeneration. Among the most important discoveries about regeneration from studies of salamanders that regenerate exceptionally well, is that both pattern-following and pattern-forming cells are required. Much progress is being made toward understanding the former cells, but little is known about the cells that control positional information and pattern formation. Within the near future, it will become possible to provide the information needed for regeneration exogenously in the form of an engineered extracellular matrix that is a biomimetic of the endogenous information. Since growth factors (morphogens) can control pattern formation, an engineered grid could be based on spatially organized patterns of sulfation of glycosaminoglycans that control the behavior of cells by modulating morphogen activity. Progress in engineering the positional information grid for regeneration will necessitate learning the sulfation codes associated with successful regeneration in animals such as salamanders.
遗传学和基因组学所产生的信息呈爆炸式增长，这使人们认识到生物之间、发育与再生过程之间基因调控网络的保守性。随着知识的不断增加，通过治疗手段干预这些网络从而诱导再生的新疗法将成为可能。于是问题就变成了如何去做，而非何时去尝试。我们的论点是，时机已经成熟，通过将发育生物学家提供的见解与生物材料工程师正在开发的技术相结合，就能实现工程化再生的目标。因此，我们将再生工程视为朝着实现人类再生目标迈出的下一步。在对再生能力极强的蝾螈进行的研究中，关于再生的最重要发现之一是，既需要遵循模式的细胞，也需要形成模式的细胞。在理解前者方面已取得很大进展，但对于控制位置信息和模式形成的细胞却知之甚少。在不久的将来，有可能以一种模拟内源性信息的工程化细胞外基质的形式，外源提供再生所需的信息。由于生长因子（形态发生素）可以控制模式形成，一个工程化网格可以基于糖胺聚糖硫酸化的空间组织模式构建，这种模式通过调节形态发生素的活性来控制细胞行为。要在再生的位置信息网格工程方面取得进展，就必须了解与蝾螈等动物成功再生相关的硫酸化编码。
