Cells from discarded dressings differentiate chronic from acute wounds in patients with Epidermolysis Bullosa

Ignacia Fuentes,Pilar Morandé,Raymond J Cho,Glenda Cofré-Araneda,María Joao Yubero,M Peter Marinkovich,B Tockner ,Luis H Eraso,Boris Rebolledo‐Jaramillo ,Anja Diem,Josefina Piñón Hofbauer ,Yessia Hidalgo,Joyce Teng ,Timothy G Webster ,Heather I Rishel ,Alfred Klausegger,Francis Palisson,Olga Figuera,Christina Guttmann‐Gruber ,Marco Di Prisco ,Andrew P South

doi:10.1038/s41598-020-71794-1

Abstract

Impaired wound healing complicates a wide range of diseases and represents a major cost to healthcare systems. Here we describe the use of discarded wound dressings as a novel, cost effective, accessible, and non-invasive method of isolating viable human cells present at the site of skin wounds. By analyzing 133 discarded wound dressings from 51 patients with the inherited skin-blistering disease epidermolysis bullosa (EB), we show that large numbers of cells, often in excess of 100 million per day, continually infiltrate wound dressings. We show, that the method is able to differentiate chronic from acute wounds, identifying significant increases in granulocytes in chronic wounds, and we show that patients with the junctional form of EB have significantly more cells infiltrating their wounds compared with patients with recessive dystrophic EB. Finally, we identify subsets of granulocytes and T lymphocytes present in all wounds paving the way for single cell profiling of innate and adaptive immune cells with relevance to wound pathologies. In summary, our study delineates findings in EB that have potential relevance for all chronic wounds, and presents a method of cellular isolation that has wide reaching clinical application.

Highlights

Impaired wound healing complicates a wide range of diseases and represents a major cost to healthcare systems
Many studies have identified evidence of increased cytokines associated with neutrophils in chronic wounds, suggesting that persistence of neutrophils, one of the first immune cell populations to migrate into wounds during the inflammatory stage, is a feature of chronic w ounds[11,12,13]
junctional EB (JEB) patient wounds (n = 30) yielded more cells than recessive dystrophic EB (RDEB) patient wounds (n = 82, median 17 × 106 compared with 58 × 106, p = 0.007) (Fig. 2E) and no difference in wound size was observed comparing JEB with RDEB

Summary

Introduction

Impaired wound healing complicates a wide range of diseases and represents a major cost to healthcare systems. Many studies have identified evidence of increased cytokines associated with neutrophils in chronic wounds, suggesting that persistence of neutrophils, one of the first immune cell populations to migrate into wounds during the inflammatory stage, is a feature of chronic w ounds[11,12,13]. These observations in patients are supported, and often directed, by studies in rodents[12,14]. Identifying the reasons why certain wounds heal and why others do not will greatly increase our understanding of EB wound healing and will direct clinical management as well as therapeutic discovery

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Conclusion