The capacity to regenerate entire body parts, tissues, and organs had generally been thought to be lost in evolution with very few exceptions (e.g. the liver) surviving in mammals. The discovery of the MRL mouse and the elucidation of the underlying molecular pathway centering around hypoxia inducible factor, HIF-1α, has allowed a drug and materials approach to regeneration in mice and hopefully humans. The HIF-1α pathway is ancient and permitted the transition from unicellular to multicellular organisms. Furthermore, HIF-1α and its regulation by PHDs, important oxygen sensors in the cell, provides a perfect drug target. We review the historical background of regeneration biology, the discovery of the MRL mouse, and its underlying biology, and novel approaches to drugs, targets, and delivery systems (see Fig. 1).

人们普遍认为，在哺乳动物的体内，除了极少数例外（例如肝脏）外，其整个身体，组织和器官的再生能力都在进化中丧失了。MRL小鼠的发现以及围绕缺氧诱导因子HIF-1α的潜在分子途径的阐明，已经为药物和材料在小鼠乃至人类中的再生提供了途径。HIF-1α途径很古老，可以从单细胞生物过渡到多细胞生物。此外，HIF-1α及其受PHD（细胞中重要的氧气传感器）的调控，提供了理想的药物靶标。我们回顾了再生生物学的历史背景，MRL小鼠的发现及其基础生物学以及药物，靶标和递送系统的新颖方法（见图1）。