Murine Model of Wound Healing

Murine Model of Wound Healing
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DOI:
10.3791/50265
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发表时间:
2013-05-01
影响因子:
1.2
通讯作者:
Bursill, Christina A.
Bursill, Christina A.
中科院分区:
综合性期刊4区
文献类型:
--
作者:
Dunn, Louise;Prosser, Hamish C. G.;Bursill, Christina A.

文献摘要

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伤口愈合和修复是人类生命中最复杂的生物过程。受伤后,多种生物途径被激活。例如,发生在糖尿病患者中的伤口愈合受损可能导致严重的不利结果,例如截肢。因此,开发促进伤口修复的新型药剂的动力越来越大。这些测试仅限于大型动物模型,如猪,这往往是不切实际的。小鼠代表了理想的临床前模型,因为它们是经济的并且适合于遗传操作,这允许进行机理研究。然而,小鼠的伤口愈合与人类的伤口愈合根本不同,因为它主要通过收缩发生。我们的小鼠模型通过在伤口周围加入夹板克服了这一点。通过夹板固定伤口,修复过程依赖于上皮形成、细胞增殖和血管生成,这密切反映了人类伤口愈合的生物学过程。虽然需要一致性和护理,但这种鼠模型不涉及复杂的手术技术,并且允许对可能促进血管生成或抑制炎症的有前景的药物进行稳健的测试。此外,每只小鼠作为其自身对照,因为制备了两个伤口,使得能够在同一动物上施用测试化合物和媒介物对照。总之,我们展示了一个实用的,易于学习的,强大的伤口愈合模型,这是可比的人类。
Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. Impaired wound healing, which occurs in diabetic patients for example, can lead to severe unfavorable outcomes such as amputation. There is, therefore, an increasing impetus to develop novel agents that promote wound repair. The testing of these has been limited to large animal models such as swine, which are often impractical. Mice represent the ideal preclinical model, as they are economical and amenable to genetic manipulation, which allows for mechanistic investigation. However, wound healing in a mouse is fundamentally different to that of humans as it primarily occurs via contraction. Our murine model overcomes this by incorporating a splint around the wound. By splinting the wound, the repair process is then dependent on epithelialization, cellular proliferation and angiogenesis, which closely mirror the biological processes of human wound healing. Whilst requiring consistency and care, this murine model does not involve complicated surgical techniques and allows for the robust testing of promising agents that may, for example, promote angiogenesis or inhibit inflammation. Furthermore, each mouse acts as its own control as two wounds are prepared, enabling the application of both the test compound and the vehicle control on the same animal. In conclusion, we demonstrate a practical, easy-to-learn, and robust model of wound healing, which is comparable to that of humans.