Theranostics 2019; 9(2):477-490. doi:10.7150/thno.29361

Research Paper

Argon Mitigates Impaired Wound Healing Process and Enhances Wound Healing In Vitro and In Vivo

Jiaolin Ning1,2*, Hailin Zhao2*, Bin Chen1*, Emma Zheling Mi2*, Zhen Yang1, Wenhan Qing1, Kwok Wing Joyce Lam2, Bin Yi1, Qian Chen1,2, Jianteng Gu1✉, Thomas Ichim3, Vladimir Bogin3, Kaizhi Lu1✉, Daqing Ma2✉

1. Department of Anesthesiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
2. Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK
3. Nobilis Therapeutics, Inc. 3042 NW Monte Vista Ter, Portland, OR 97210
*These authors contributed equally to this work.

Abstract

Diabetic foot ulcers are associated with significant morbidity and mortality, and current treatments are far from optimal. Chronic wounds in diabetes are characterised by impaired angiogenesis, leukocyte function, fibroblast proliferation, and keratinocyte migration and proliferation.

Methods: We tested the effect of exposure to argon gas on endothelial cell, fibroblast, macrophage and keratinocyte cell cultures in vitro and in vivo of a streptozotocin-induced diabetic mouse model.

Results: Exposure to normobaric argon gas promotes multiple steps of the wound healing process. Argon accelerated angiogenesis, associated with upregulation of pro-angiogenic Angiopoietin-1 and vascular endothelial growth factor (VEGF) signalling in vitro and in vivo. Treatment with argon enhanced expression of transforming growth factor (TGF)-β, early recruitment of macrophages and keratinocyte proliferation. Argon had a pro-survival effect, inducing expression of cytoprotective mediators B-cell lymphoma 2 and heme oxygenase 1. Argon was able to accelerate wound closure in a diabetic mouse model.

Conclusion: Together these findings indicate that argon gas may be a promising candidate for clinical use in treatment of diabetic ulcers.

Keywords: diabetes, wound healing, argon, angiogenesis, VEGF, TGF-β

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How to cite this article:
Ning J, Zhao H, Chen B, Mi EZ, Yang Z, Qing W, Lam KWJ, Yi B, Chen Q, Gu J, Ichim T, Bogin V, Lu K, Ma D. Argon Mitigates Impaired Wound Healing Process and Enhances Wound Healing In Vitro and In Vivo. Theranostics 2019; 9(2):477-490. doi:10.7150/thno.29361. Available from http://www.thno.org/v09p0477.htm