Stimulating regeneration of complex tissues and organs after injury to effect complete structural and functional repair, is an attractive therapeutic option that would revolutionize clinical medicine. Compared to many metazoan phyla that show extraordinary regenerative capacity, which in some instances persists throughout life, regeneration in mammalians, particularly humans, is limited or absent. Here we consider recent insights in the elucidation of molecular mechanisms of regeneration that have come from studies of tissue homeostasis and injury repair in mammalian tissues that span the spectrum from little or no self-renewal, to those showing active cell turnover throughout life. These studies highlight the diversity of factors that constrain regeneration, including immune responses, extracellular matrix composition, age, injury type, physiological adaptation, and angiogenic and neurogenic capacity. Despite these constraints, much progress has been made in elucidating key molecular mechanisms that may provide therapeutic targets for the development of future regenerative therapies, as well as previously unidentified developmental paradigms and windows-of-opportunity for improved regenerative repair.

刺激损伤后复杂组织和器官的再生以实现完整的结构和功能修复，是一种有吸引力的治疗选择，它将彻底改变临床医学。与显示出非凡的再生能力的后生门相比，后者在某些情况下会持续一生，而哺乳动物，尤其是人类的再生则受到限制或缺乏。在这里，我们考虑了阐明分子机制的最新见解，这些分子机制来自对哺乳动物组织进行组织稳态和损伤修复的研究，这些研究涵盖了从很少或没有自我更新的光谱，到显示整个生命周期活跃的细胞更新。这些研究强调了限制再生的因素的多样性，包括免疫应答，细胞外基质组成，年龄，损伤类型，生理适应性以及血管生成和神经生成能力。尽管有这些限制，但在阐明可为将来的再生疗法的开发提供治疗靶标的关键分子机制方面，以及在改善再生修复方面尚未确定的发展范式和机会之窗方面，已经取得了很大进展。