Predicting the road not taken

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Science Translational Medicine  11 Feb 2015:
Vol. 7, Issue 274, pp. 274ec26
DOI: 10.1126/scitranslmed.aaa8312

Chronic skin ulcers can be treated, but sometimes they heal and sometimes they don’t. To better understand why, Nassiri et al. hypothesized that because immune cells are central to the inflammatory response and actively regulate wound healing, there may be a healing “signature” hidden within macrophage phenotypes. The macrophage M1 phenotype is associated with inflammation, whereas the M2 phenotype signals healing. To search for a clinically applicable “rule” for healing, the authors created a scoring system: the ratio of four M1 genes (VEGF, CCR7, CD80, and IL1β) to three M2 genes (MRC1, PDGFB, and TIMP3). Using patient data from burn wounds, they found that the score increased right after injury, then decreased about 1 week later, suggesting a transformation from M1 to M2 during healing. In a pilot study of 10 patients with chronic diabetic foot ulcers [that had been open for 8 weeks], healed ulcers showed a reduction in M1/M2 score over time, whereas the scores for nonhealing ulcers continued to increase. Interestingly, the initial score was higher for wounds that eventually healed, indicating a prominent, early role for inflammation in successful healing. The score at 4 weeks predicted healing by 12 weeks, which could alert clinicians to which ulcers would not heal well and thus change management of chronic diabetic ulcers.

S. Nassiri et al., Relative expression of pro-inflammatory and anti-inflammatory genes reveals differences between healing and nonhealing human chronic diabetic foot ulcers. J. Invest. Dermatol. 10.1038/jid.2015.30 (2015). [Full Text]

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