Characterization of adipose tissue macrophages and adipose-derived stem cells in critical wounds.

Bong-Sung Kim,Ruedger Kopp,Bergita Ganse,Katrin Springenberg-Jung,Daniel Heinrichs,Norbert Pallua,Jan Philipp Stromps,Juergen Bernhagen,Richard Bucala,Pathricia V Tilstam,Corinna Schmitz,Arne Hendrick Boecker,Soo Seok Hwang,Matthias Knobe

doi:10.7717/peerj.2824

Abstract

BackgroundSubcutaneous adipose tissue is a rich source of adipose tissue macrophages and adipose-derived stem cells which both play a key role in wound repair. While macrophages can be divided into the classically-activated M1 and the alternatively-activated M2 phenotype, ASCs are characterized by the expression of specific stem cell markers.MethodsIn the present study, we have investigated the expression of common macrophage polarization and stem cell markers in acutely inflamed adipose tissue. Subcutaneous adipose tissue adjacent to acutely inflamed wounds of 20 patients and 20 healthy subjects were harvested and underwent qPCR and flow cytometry analysis.ResultsExpression levels of the M1-specific markers CD80, iNOS, and IL-1b were significantly elevated in inflammatory adipose tissue when compared to healthy adipose tissue, whereas the M2-specific markers CD163 and TGF-β were decreased. By flow cytometry, a significant shift of adipose tissue macrophage populations towards the M1 phenotype was confirmed. Furthermore, a decrease in the mesenchymal stem cell markers CD29, CD34, and CD105 was observed whereas CD73 and CD90 remained unchanged.DiscussionThis is the first report describing the predominance of M1 adipose tissue macrophages and the reduction of stem cell marker expression in acutely inflamed, non-healing wounds.

Highlights

Wound healing disorders remain a challenge for specialists and the burden to global healthcare systems is substantial (Mudge, 2015)
We found that Inflammatory adipose tissue (IAT) showed an increase in the messenger RNA (mRNA) expression of the M1-related genes cluster of differentiation 80 (CD80), inducible nitric oxide synthase (iNOS), and IL-β, and a down-regulation of the M2-related genes CD163, TGFβ
We observed a marked decrease in the mRNA expression of the stem cell marker CD29, CD34, and CD105 in IAT compared to healthy patients with normal adipose tissue (HAT), while the levels CD73 and CD90 were unaffected

Summary

Introduction

Wound healing disorders remain a challenge for specialists and the burden to global healthcare systems is substantial (Mudge, 2015). Subcutaneous adipose tissue is a rich source of adipose tissue macrophages and adipose-derived stem cells which both play a key role in wound repair. While macrophages can be divided into the classically-activated M1 and the alternatively-activated M2 phenotype, ASCs are characterized by the expression of specific stem cell markers. We have investigated the expression of common macrophage polarization and stem cell markers in acutely inflamed adipose tissue. Subcutaneous adipose tissue adjacent to acutely inflamed wounds of 20 patients and 20 healthy subjects were harvested and underwent qPCR and flow cytometry analysis. This is the first report describing the predominance of M1 adipose tissue macrophages and the reduction of stem cell marker expression in acutely inflamed, non-healing wounds

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Discussion

Conclusion