Digit Tip Regeneration: Merging Regeneration Biology with Regenerative Medicine
Digit Tip Regeneration: Merging Regeneration Biology with Regenerative Medicine
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DOI：
10.1002/sctm.17-0236
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发表时间：
2018-03-01
影响因子：
6
通讯作者：
Muneoka, Ken
中科院分区：
文献类型：
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作者：
Dolan, Connor P.;Dawson, Lindsay A.;Muneoka, Ken
再生生物学是对具有内源性再生能力的生物体的研究，而再生医学则专注于为无法再生的人类损伤提供工程解决方案。虽然这两个领域在方法上有着根本的不同，但在哺乳动物再生模型方面有着明显的界面。指尖是人类肢体中唯一具有再生能力的部分，再生小鼠指尖已成为研究临床相关再生反应的模型。在这篇文章中，我们将讨论如何研究指尖再生确定再生反应的关键组成部分，以及如何了解内源性再生可以导致扩大非再生性截肢伤口的再生能力。这些研究表明，再生能力不足的伤口可以通过启动多组织反应，最终导致结构再生，从而对单独的形态发生剂治疗产生反应。此外，非再生性伤口的愈合过程被发现通过无反应，反应和无反应阶段循环，我们称之为再生窗口的反应阶段。我们还发现，成熟愈合的截肢伤口的反应性可以通过再损伤重新激活，因此非再生伤口保留了再生的潜力。我们认为，再生能力不足的损伤具有休眠的再生潜力，可以通过特定的形态发生剂的靶向治疗激活。我们认为，未来的再生医学疗法应该旨在促进，而不是取代，再生反应。
Regeneration Biology is the study of organisms with endogenous regenerative abilities, whereas Regenerative Medicine focuses on engineering solutions for human injuries that do not regenerate. While the two fields are fundamentally different in their approach, there is an obvious interface involving mammalian regeneration models. The fingertip is the only part of the human limb that is regeneration-competent and the regenerating mouse digit tip has emerged as a model to study a clinically relevant regenerative response. In this article, we discuss how studies of digit tip regeneration have identified critical components of the regenerative response, and how an understanding of endogenous regeneration can lead to expanding the regenerative capabilities of nonregenerative amputation wounds. Such studies demonstrate that regeneration-incompetent wounds can respond to treatment with individual morphogenetic agents by initiating a multi-tissue response that culminates in structural regeneration. In addition, the healing process of nonregenerative wounds are found to cycle through nonresponsive, responsive and nonresponsive phases, and we call the responsive phase the Regeneration Window. We also find the responsiveness of mature healed amputation wounds can be reactivated by reinjury, thus nonregenerated wounds retain a potential for regeneration. We propose that regeneration-incompetent injuries possess dormant regenerative potential that can be activated by targeted treatment with specific morphogenetic agents. We believe that future Regenerative Medicine-based-therapies should be designed to promote, not replace, regenerative responses.