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Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization

Overview of attention for article published in Inflammation and Regeneration, October 2023
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Title
Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization
Published in
Inflammation and Regeneration, October 2023
DOI 10.1186/s41232-023-00302-5
Pubmed ID
Authors

Tina Rauchenwald, Florian Handle, Catherine E. Connolly, Antonia Degen, Christof Seifarth, Martin Hermann, Christoph H. Tripp, Doris Wilflingseder, Susanne Lobenwein, Dragana Savic, Leo Pölzl, Evi M. Morandi, Dolores Wolfram, Ira-Ida Skvortsova, Patrizia Stoitzner, Johannes Haybaeck, Marko Konschake, Gerhard Pierer, Christian Ploner

Abstract

Chronic non-healing wounds pose a global health challenge. Under optimized conditions, skin wounds heal by the formation of scar tissue. However, deregulated cell activation leads to persistent inflammation and the formation of granulation tissue, a type of premature scar tissue without epithelialization. Regenerative cells from the wound periphery contribute to the healing process, but little is known about their cellular fate in an inflammatory, macrophage-dominated wound microenvironment. We examined CD45-/CD31-/CD34+ preadipocytes and CD68+ macrophages in human granulation tissue from pressure ulcers (n=6) using immunofluorescence, immunohistochemistry, and flow cytometry. In vitro, we studied macrophage-preadipocyte interactions using primary human adipose-derived stem cells (ASCs) exposed to conditioned medium harvested from IFNG/LPS (M1)- or IL4/IL13 (M2)-activated macrophages. Macrophages were derived from THP1 cells or CD14+ monocytes. In addition to confocal microscopy and flow cytometry, ASCs were analyzed for metabolic (OXPHOS, glycolysis), morphological (cytoskeleton), and mitochondrial (ATP production, membrane potential) changes. Angiogenic properties of ASCs were determined by HUVEC-based angiogenesis assay. Protein and mRNA levels were assessed by immunoblotting and quantitative RT-PCR. CD45-/CD31-/CD34+ preadipocytes were observed with a prevalence of up to 1.5% of total viable cells in human granulation tissue. Immunofluorescence staining suggested a spatial proximity of these cells to CD68+ macrophages in vivo. In vitro, ASCs exposed to M1, but not to M2 macrophage secretome showed a pro-fibrotic response characterized by stress fiber formation, elevated alpha smooth muscle actin (SMA), and increased expression of integrins ITGA5 and ITGAV. Macrophage-secreted IL1B and TGFB1 mediated this response via the PI3K/AKT and p38-MAPK pathways. In addition, ASCs exposed to M1-inflammatory stress demonstrated reduced migration, switched to a glycolysis-dominated metabolism with reduced ATP production, and increased levels of inflammatory cytokines such as IL1B, IL8, and MCP1. Notably, M1 but not M2 macrophages enhanced the angiogenic potential of ASCs. Preadipocyte fate in wound tissue is influenced by macrophage polarization. Pro-inflammatory M1 macrophages induce a pro-fibrotic response in ASCs through IL1B and TGFB1 signaling, while anti-inflammatory M2 macrophages have limited effects. These findings shed light on cellular interactions in chronic wounds and provide important information for the potential therapeutic use of ASCs in human wound healing.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 5 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 1 20%
Student > Bachelor 1 20%
Unknown 3 60%
Readers by discipline Count As %
Unspecified 1 20%
Biochemistry, Genetics and Molecular Biology 1 20%
Unknown 3 60%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 October 2023.
All research outputs
#16,347,178
of 25,808,886 outputs
Outputs from Inflammation and Regeneration
#141
of 265 outputs
Outputs of similar age
#173,240
of 365,616 outputs
Outputs of similar age from Inflammation and Regeneration
#7
of 10 outputs
Altmetric has tracked 25,808,886 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 265 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.7. This one is in the 43rd percentile – i.e., 43% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 365,616 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 3 of them.