Photodynamic therapy accelerates skin wound healing through promoting re-epithelialization

Author:

Yang Zengjun1,Hu Xiaohong23,Zhou Lina4,He Yaxiong1,Zhang Xiaorong23,Yang Jiacai23,Ju Zhenyu5,Liou Yih-Cherng6,Shen Han-Ming7,Luo Gaoxing23,Hamblin Michael R89,He Weifeng23,Yin Rui1

Affiliation:

1. Department of Dermatology, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China

2. State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China

3. Chongqing Key Laboratory for Disease Proteomics, No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China

4. Department of Endocrinology, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China

5. Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, No. 601 Huangpu Street, Tianhe District, Guangzhou, Guangdong Province, 510632, China

6. Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, 117543, Singapore

7. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 14 Science Drive 4, 117543, Singapore

8. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA, 02114, USA

9. Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, 17011 South Africa

Abstract

Abstract Background Epidermal stem cells (EpSCs) that reside in cutaneous hair follicles and the basal layer of the epidermis are indispensable for wound healing and skin homeostasis. Little is known about the effects of photochemical activation on EpSC differentiation, proliferation and migration during wound healing. The present study aimed to determine the effects of photodynamic therapy (PDT) on wound healing in vivo and in vitro. Methods We created mouse full-thickness skin resection models and applied 5-aminolevulinic acid (ALA) for PDT to the wound beds. Wound healing was analysed by gross evaluation and haematoxylin–eosin staining in vivo. In cultured EpSCs, protein expression was measured using flow cytometry and immunohistochemistry. Cell migration was examined using a scratch model; apoptosis and differentiation were measured using flow cytometry. Results PDT accelerated wound closure by enhancing EpSC differentiation, proliferation and migration, thereby promoting re-epithelialization and angiogenesis. PDT inhibited inflammatory infiltration and expression of proinflammatory cytokines, whereas the secretion of growth factors was greater than in other groups. The proportion of transient amplifying cells was significantly greater in vivo and in vitro in the PDT groups. EpSC migration was markedly enhanced after ALA-induced PDT. Conclusions Topical ALA-induced PDT stimulates wound healing by enhancing re-epithelialization, promoting angiogenesis as well as modulating skin homeostasis. This work provides a preliminary theoretical foundation for the clinical administration of topical ALA-induced PDT in skin wound healing.

Funder

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

Subject

Critical Care and Intensive Care Medicine,Dermatology,Biomedical Engineering,Emergency Medicine,Immunology and Allergy,Surgery

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