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

Author:

Kim Bong-Sung123,Tilstam Pathricia V.2,Springenberg-Jung Katrin1,Boecker Arne Hendrick1,Schmitz Corinna3,Heinrichs Daniel3,Hwang Soo Seok4,Stromps Jan Philipp1,Ganse Bergita5,Kopp Ruedger6,Knobe Matthias5,Bernhagen Juergen78,Pallua Norbert1,Bucala Richard2

Affiliation:

1. Plastic and Reconstructive Surgery, Hand Surgery—Burn Center, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany

2. Department of Medicine, Yale University, New Haven, United States

3. Institute of Biochemistry and Molecular Cell Biology, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany

4. Department of Immunology, Yale University, New Haven, United States

5. Department of Orthopedic Trauma Surgery, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany

6. Department of Intensive Care Medicine, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany

7. Department of Vascular Biology, Institute for Stroke and Dementia Research, Ludwig-Maximilians-Universität München (LMU), Munich, Germany

8. Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-Universität München (LMU), Munich, Germany

Abstract

Background 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. Methods In 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. Results Expression 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. Discussion 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.

Funder

Medical Faculty at the RWTH Aachen University

German Research Foundation (Deutsche Forschungsgemeinschaft (DFG)

National Institute of Health (NIH)

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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