Effect of Inflammatory Microenvironment on the Regenerative Capacity of Adipose-Derived Mesenchymal Stem Cells
Adipose-derived mesenchymal stem cells are increasingly being used in regenerative medicine as cell therapy targets, including in the treatment of burns and ulcers. The regenerative potential of AD-MSCs and some of their immunological properties are known from in vitro studies; however, in clinical...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/15/1966 |
| _version_ | 1797586919746437120 |
|---|---|
| author | Diána Szűcs Vanda Miklós Tamás Monostori Melinda Guba Anikó Kun-Varga Szilárd Póliska Erika Kis Balázs Bende Lajos Kemény Zoltán Veréb |
| author_facet | Diána Szűcs Vanda Miklós Tamás Monostori Melinda Guba Anikó Kun-Varga Szilárd Póliska Erika Kis Balázs Bende Lajos Kemény Zoltán Veréb |
| author_sort | Diána Szűcs |
| collection | DOAJ |
| description | Adipose-derived mesenchymal stem cells are increasingly being used in regenerative medicine as cell therapy targets, including in the treatment of burns and ulcers. The regenerative potential of AD-MSCs and some of their immunological properties are known from in vitro studies; however, in clinical applications, cells are used in non-ideal conditions and can behave differently in inflammatory environments, affecting the efficacy and outcome of therapy. Our aim was to investigate and map the pathways that the inflammatory microenvironment can induce in these cells. High-throughput gene expression assays were performed on AD-MSCs activated with LPS and TNFα. Analysis of RNA-Seq data showed that control, LPS-treated and TNFα-treated samples exhibited distinct gene expression patterns. LPS treatment increased the expression of 926 genes and decreased the expression of 770 genes involved in cell division, DNA repair, the cell cycle, and several metabolic processes. TNFα treatment increased the expression of 174 genes and decreased the expression of 383 genes, which are related to cell division, the immune response, cell proliferation, and differentiation. We also map the biological pathways by further investigating the most altered genes using the Gene Ontology and KEGG databases. Secreted cytokines, which are important in the immunological response, were also examined at the protein level, and a functional assay was performed to assess wound healing. Activated AD-MSC increased the secretion of IL-6, IL-8 and CXCL-10, and also the closure of wounds. AD-MSCs presented accelerated wound healing under inflammation conditions, suggesting that we could use this cell in clinical application. |
| first_indexed | 2024-03-11T00:29:01Z |
| format | Article |
| id | doaj.art-0c405c78c94c496abce71d9b546f32e5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T00:29:01Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-0c405c78c94c496abce71d9b546f32e52023-11-18T22:45:04ZengMDPI AGCells2073-44092023-07-011215196610.3390/cells12151966Effect of Inflammatory Microenvironment on the Regenerative Capacity of Adipose-Derived Mesenchymal Stem CellsDiána Szűcs0Vanda Miklós1Tamás Monostori2Melinda Guba3Anikó Kun-Varga4Szilárd Póliska5Erika Kis6Balázs Bende7Lajos Kemény8Zoltán Veréb9Regenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryBiobank, University of Szeged, 6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryGenomic Medicine and Bioinformatics Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDermatosurgery and Plastic Surgery, Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryDermatosurgery and Plastic Surgery, Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, HungaryAdipose-derived mesenchymal stem cells are increasingly being used in regenerative medicine as cell therapy targets, including in the treatment of burns and ulcers. The regenerative potential of AD-MSCs and some of their immunological properties are known from in vitro studies; however, in clinical applications, cells are used in non-ideal conditions and can behave differently in inflammatory environments, affecting the efficacy and outcome of therapy. Our aim was to investigate and map the pathways that the inflammatory microenvironment can induce in these cells. High-throughput gene expression assays were performed on AD-MSCs activated with LPS and TNFα. Analysis of RNA-Seq data showed that control, LPS-treated and TNFα-treated samples exhibited distinct gene expression patterns. LPS treatment increased the expression of 926 genes and decreased the expression of 770 genes involved in cell division, DNA repair, the cell cycle, and several metabolic processes. TNFα treatment increased the expression of 174 genes and decreased the expression of 383 genes, which are related to cell division, the immune response, cell proliferation, and differentiation. We also map the biological pathways by further investigating the most altered genes using the Gene Ontology and KEGG databases. Secreted cytokines, which are important in the immunological response, were also examined at the protein level, and a functional assay was performed to assess wound healing. Activated AD-MSC increased the secretion of IL-6, IL-8 and CXCL-10, and also the closure of wounds. AD-MSCs presented accelerated wound healing under inflammation conditions, suggesting that we could use this cell in clinical application.https://www.mdpi.com/2073-4409/12/15/1966adipose-derived mesenchymal stem cellslipopolysaccharidetumor necrosis factor αinflammationregenerative medicine |
| spellingShingle | Diána Szűcs Vanda Miklós Tamás Monostori Melinda Guba Anikó Kun-Varga Szilárd Póliska Erika Kis Balázs Bende Lajos Kemény Zoltán Veréb Effect of Inflammatory Microenvironment on the Regenerative Capacity of Adipose-Derived Mesenchymal Stem Cells Cells adipose-derived mesenchymal stem cells lipopolysaccharide tumor necrosis factor α inflammation regenerative medicine |
| title | Effect of Inflammatory Microenvironment on the Regenerative Capacity of Adipose-Derived Mesenchymal Stem Cells |
| title_full | Effect of Inflammatory Microenvironment on the Regenerative Capacity of Adipose-Derived Mesenchymal Stem Cells |
| title_fullStr | Effect of Inflammatory Microenvironment on the Regenerative Capacity of Adipose-Derived Mesenchymal Stem Cells |
| title_full_unstemmed | Effect of Inflammatory Microenvironment on the Regenerative Capacity of Adipose-Derived Mesenchymal Stem Cells |
| title_short | Effect of Inflammatory Microenvironment on the Regenerative Capacity of Adipose-Derived Mesenchymal Stem Cells |
| title_sort | effect of inflammatory microenvironment on the regenerative capacity of adipose derived mesenchymal stem cells |
| topic | adipose-derived mesenchymal stem cells lipopolysaccharide tumor necrosis factor α inflammation regenerative medicine |
| url | https://www.mdpi.com/2073-4409/12/15/1966 |
| work_keys_str_mv | AT dianaszucs effectofinflammatorymicroenvironmentontheregenerativecapacityofadiposederivedmesenchymalstemcells AT vandamiklos effectofinflammatorymicroenvironmentontheregenerativecapacityofadiposederivedmesenchymalstemcells AT tamasmonostori effectofinflammatorymicroenvironmentontheregenerativecapacityofadiposederivedmesenchymalstemcells AT melindaguba effectofinflammatorymicroenvironmentontheregenerativecapacityofadiposederivedmesenchymalstemcells AT anikokunvarga effectofinflammatorymicroenvironmentontheregenerativecapacityofadiposederivedmesenchymalstemcells AT szilardpoliska effectofinflammatorymicroenvironmentontheregenerativecapacityofadiposederivedmesenchymalstemcells AT erikakis effectofinflammatorymicroenvironmentontheregenerativecapacityofadiposederivedmesenchymalstemcells AT balazsbende effectofinflammatorymicroenvironmentontheregenerativecapacityofadiposederivedmesenchymalstemcells AT lajoskemeny effectofinflammatorymicroenvironmentontheregenerativecapacityofadiposederivedmesenchymalstemcells AT zoltanvereb effectofinflammatorymicroenvironmentontheregenerativecapacityofadiposederivedmesenchymalstemcells |