DeFrates Kelsey G, Franco Daniela, Heber-Katz Ellen, Messersmith Phillip B
Department of Bioengineering and Materials Science and Engineering, University of California, Berkeley, CA, USA.
Laboratory of Regenerative Medicine, Lankenau Institute for Medical Research, Wynnewood, PA, USA.
Biomaterials. 2021 Feb;269:120646. doi: 10.1016/j.biomaterials.2020.120646. Epub 2021 Jan 9.
Historically, the field of regenerative medicine has aimed to heal damaged tissue through the use of biomaterials scaffolds or delivery of foreign progenitor cells. Despite 30 years of research, however, translation and commercialization of these techniques has been limited. To enable mammalian regeneration, a more practical approach may instead be to develop therapies that evoke endogenous processes reminiscent of those seen in innate regenerators. Recently, investigations into tadpole tail regrowth, zebrafish limb restoration, and the super-healing Murphy Roths Large (MRL) mouse strain, have identified ancient oxygen-sensing pathways as a possible target to achieve this goal. Specifically, upregulation of the transcription factor, hypoxia-inducible factor one alpha (HIF-1α) has been shown to modulate cell metabolism and plasticity, as well as inflammation and tissue remodeling, possibly priming injuries for regeneration. Since HIF-1α signaling is conserved across species, environmental or pharmacological manipulation of oxygen-dependent pathways may elicit a regenerative response in non-healing mammals. In this review, we will explore the emerging role of HIF-1α in mammalian healing and regeneration, as well as attempts to modulate protein stability through hyperbaric oxygen treatment, intermittent hypoxia therapy, and pharmacological targeting. We believe that these therapies could breathe new life into the field of regenerative medicine.
从历史上看，再生医学领域一直致力于通过使用生物材料支架或递送外源祖细胞来修复受损组织。然而，尽管经过了30年的研究，这些技术的转化和商业化仍然有限。为了实现哺乳动物的再生，一种更实际的方法可能是开发能够引发内源性过程的疗法，这些过程让人联想到先天再生者所具有的那些过程。最近，对蝌蚪尾巴再生、斑马鱼肢体修复以及超级愈合的墨菲罗斯大（MRL）小鼠品系的研究，已经确定古老的氧感应途径是实现这一目标的一个可能靶点。具体而言，转录因子缺氧诱导因子1α（HIF-1α）的上调已被证明可调节细胞代谢和可塑性，以及炎症和组织重塑，可能为再生启动损伤。由于HIF-1α信号在物种间是保守的，对氧依赖途径的环境或药理学操纵可能会在无法愈合的哺乳动物中引发再生反应。在这篇综述中，我们将探讨HIF-1α在哺乳动物愈合和再生中的新作用，以及通过高压氧治疗、间歇性缺氧疗法和药理学靶向调节蛋白质稳定性的尝试。我们相信这些疗法能够为再生医学领域注入新的活力。
