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Elife. 2017 May 16;6. pii: e24623. doi: 10.7554/eLife.24623.

Macrophages are necessary for epimorphic regeneration in African spiny mice.

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Department of Biology, University of Kentucky, Lexington, United States.
Department of Physiology, University of Kentucky, Lexington, United States.
Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, United States.


How the immune system affects tissue regeneration is not well understood. In this study, we used an emerging mammalian model of epimorphic regeneration, the African spiny mouse, to examine cell-based inflammation and tested the hypothesis that macrophages are necessary for regeneration. By directly comparing inflammatory cell activation in a 4 mm ear injury during regeneration (Acomys cahirinus) and scarring (Mus musculus), we found that both species exhibited an acute inflammatory response, with scarring characterized by stronger myeloperoxidase activity. In contrast, ROS production was stronger and more persistent during regeneration. By depleting macrophages during injury, we demonstrate a functional requirement for these cells to stimulate regeneration. Importantly, the spatial distribution of activated macrophage subtypes was unique during regeneration with pro-inflammatory macrophages failing to infiltrate the regeneration blastema. Together, our results demonstrate an essential role for inflammatory cells to regulate a regenerative response.


Acomys; cell biology; developmental biology; epimorphic regeneration; inflammation; macrophages; mouse; stem cells

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