Inhibition and reversal of a TGF-[beta]1 induced myofibroblast phenotype by adipose tissue-derived paracrine factors

Background Hypertrophic scarring results from myofibroblast differentiation and persistence during wound healing. Currently no effective treatment for hypertrophic scarring exists however, autologous fat grafting has been shown to improve scar elasticity, appearance, and function. The aim of this st...

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Veröffentlicht in:Stem cell research & therapy 2024-06, Vol.15 (1)
Hauptverfasser: Higginbotham, S, Workman, V. L, Giblin, A-V, Green, N. H, Lambert, D. W, Hearnden, V
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container_issue 1
container_start_page
container_title Stem cell research & therapy
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creator Higginbotham, S
Workman, V. L
Giblin, A-V
Green, N. H
Lambert, D. W
Hearnden, V
description Background Hypertrophic scarring results from myofibroblast differentiation and persistence during wound healing. Currently no effective treatment for hypertrophic scarring exists however, autologous fat grafting has been shown to improve scar elasticity, appearance, and function. The aim of this study was to understand how paracrine factors from adipose tissues and adipose-derived stromal cells (ADSC) affect fibroblast to myofibroblast differentiation. Methods The transforming growth factor-[beta]1 (TGF-[beta]1) induced model of myofibroblast differentiation was used to test the effect of conditioned media from adipose tissue, ADSC or lipid on the proportion of fibroblasts and myofibroblasts. Results Adipose tissue conditioned media inhibited the differentiation of fibroblasts to myofibroblasts but this inhibition was not observed following treatment with ADSC or lipid conditioned media. Hepatocyte growth factor (HGF) was readily detected in the conditioned medium from adipose tissue but not ADSC. Cells treated with HGF, or fortinib to block HGF, demonstrated that HGF was not responsible for the inhibition of myofibroblast differentiation. Conditioned media from adipose tissue was shown to reduce the proportion of myofibroblasts when added to fibroblasts previously treated with TGF-[beta]1, however, conditioned media treatment was unable to significantly reduce the proportion of myofibroblasts in cell populations isolated from scar tissue. Conclusions Cultured ADSC or adipocytes have been the focus of most studies, however, this work highlights the importance of considering whole adipose tissue to further our understanding of fat grafting. This study supports the use of autologous fat grafts for scar treatment and highlights the need for further investigation to determine the mechanism. Keywords: Scarring, Autologous fat grafting, Myofibroblasts, Transforming growth factor [beta]-1, Adipose-derived stromal cells
doi_str_mv 10.1186/s13287-024-03776-3
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L ; Giblin, A-V ; Green, N. H ; Lambert, D. W ; Hearnden, V</creator><creatorcontrib>Higginbotham, S ; Workman, V. L ; Giblin, A-V ; Green, N. H ; Lambert, D. W ; Hearnden, V</creatorcontrib><description>Background Hypertrophic scarring results from myofibroblast differentiation and persistence during wound healing. Currently no effective treatment for hypertrophic scarring exists however, autologous fat grafting has been shown to improve scar elasticity, appearance, and function. The aim of this study was to understand how paracrine factors from adipose tissues and adipose-derived stromal cells (ADSC) affect fibroblast to myofibroblast differentiation. Methods The transforming growth factor-[beta]1 (TGF-[beta]1) induced model of myofibroblast differentiation was used to test the effect of conditioned media from adipose tissue, ADSC or lipid on the proportion of fibroblasts and myofibroblasts. Results Adipose tissue conditioned media inhibited the differentiation of fibroblasts to myofibroblasts but this inhibition was not observed following treatment with ADSC or lipid conditioned media. Hepatocyte growth factor (HGF) was readily detected in the conditioned medium from adipose tissue but not ADSC. Cells treated with HGF, or fortinib to block HGF, demonstrated that HGF was not responsible for the inhibition of myofibroblast differentiation. Conditioned media from adipose tissue was shown to reduce the proportion of myofibroblasts when added to fibroblasts previously treated with TGF-[beta]1, however, conditioned media treatment was unable to significantly reduce the proportion of myofibroblasts in cell populations isolated from scar tissue. Conclusions Cultured ADSC or adipocytes have been the focus of most studies, however, this work highlights the importance of considering whole adipose tissue to further our understanding of fat grafting. This study supports the use of autologous fat grafts for scar treatment and highlights the need for further investigation to determine the mechanism. Keywords: Scarring, Autologous fat grafting, Myofibroblasts, Transforming growth factor [beta]-1, Adipose-derived stromal cells</description><identifier>ISSN: 1757-6512</identifier><identifier>EISSN: 1757-6512</identifier><identifier>DOI: 10.1186/s13287-024-03776-3</identifier><language>eng</language><publisher>BioMed Central Ltd</publisher><subject>Adipose tissues ; Bone morphogenetic proteins ; Care and treatment ; Ethylenediaminetetraacetic acid ; Genetic aspects ; Pharmaceutical industry ; Scientific equipment and supplies industry ; Transforming growth factors ; Wounds and injuries</subject><ispartof>Stem cell research &amp; therapy, 2024-06, Vol.15 (1)</ispartof><rights>COPYRIGHT 2024 BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27924,27925</link.rule.ids></links><search><creatorcontrib>Higginbotham, S</creatorcontrib><creatorcontrib>Workman, V. L</creatorcontrib><creatorcontrib>Giblin, A-V</creatorcontrib><creatorcontrib>Green, N. H</creatorcontrib><creatorcontrib>Lambert, D. W</creatorcontrib><creatorcontrib>Hearnden, V</creatorcontrib><title>Inhibition and reversal of a TGF-[beta]1 induced myofibroblast phenotype by adipose tissue-derived paracrine factors</title><title>Stem cell research &amp; therapy</title><description>Background Hypertrophic scarring results from myofibroblast differentiation and persistence during wound healing. Currently no effective treatment for hypertrophic scarring exists however, autologous fat grafting has been shown to improve scar elasticity, appearance, and function. The aim of this study was to understand how paracrine factors from adipose tissues and adipose-derived stromal cells (ADSC) affect fibroblast to myofibroblast differentiation. Methods The transforming growth factor-[beta]1 (TGF-[beta]1) induced model of myofibroblast differentiation was used to test the effect of conditioned media from adipose tissue, ADSC or lipid on the proportion of fibroblasts and myofibroblasts. Results Adipose tissue conditioned media inhibited the differentiation of fibroblasts to myofibroblasts but this inhibition was not observed following treatment with ADSC or lipid conditioned media. Hepatocyte growth factor (HGF) was readily detected in the conditioned medium from adipose tissue but not ADSC. Cells treated with HGF, or fortinib to block HGF, demonstrated that HGF was not responsible for the inhibition of myofibroblast differentiation. Conditioned media from adipose tissue was shown to reduce the proportion of myofibroblasts when added to fibroblasts previously treated with TGF-[beta]1, however, conditioned media treatment was unable to significantly reduce the proportion of myofibroblasts in cell populations isolated from scar tissue. Conclusions Cultured ADSC or adipocytes have been the focus of most studies, however, this work highlights the importance of considering whole adipose tissue to further our understanding of fat grafting. This study supports the use of autologous fat grafts for scar treatment and highlights the need for further investigation to determine the mechanism. 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W ; Hearnden, V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g1320-8666577bbc6e023587961f41d7e7497e40d0c69f9fe0cd9149bff368edaf73393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adipose tissues</topic><topic>Bone morphogenetic proteins</topic><topic>Care and treatment</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Genetic aspects</topic><topic>Pharmaceutical industry</topic><topic>Scientific equipment and supplies industry</topic><topic>Transforming growth factors</topic><topic>Wounds and injuries</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Higginbotham, S</creatorcontrib><creatorcontrib>Workman, V. L</creatorcontrib><creatorcontrib>Giblin, A-V</creatorcontrib><creatorcontrib>Green, N. H</creatorcontrib><creatorcontrib>Lambert, D. W</creatorcontrib><creatorcontrib>Hearnden, V</creatorcontrib><collection>Gale In Context: Science</collection><jtitle>Stem cell research &amp; therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Higginbotham, S</au><au>Workman, V. L</au><au>Giblin, A-V</au><au>Green, N. H</au><au>Lambert, D. W</au><au>Hearnden, V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition and reversal of a TGF-[beta]1 induced myofibroblast phenotype by adipose tissue-derived paracrine factors</atitle><jtitle>Stem cell research &amp; therapy</jtitle><date>2024-06-13</date><risdate>2024</risdate><volume>15</volume><issue>1</issue><issn>1757-6512</issn><eissn>1757-6512</eissn><abstract>Background Hypertrophic scarring results from myofibroblast differentiation and persistence during wound healing. Currently no effective treatment for hypertrophic scarring exists however, autologous fat grafting has been shown to improve scar elasticity, appearance, and function. The aim of this study was to understand how paracrine factors from adipose tissues and adipose-derived stromal cells (ADSC) affect fibroblast to myofibroblast differentiation. Methods The transforming growth factor-[beta]1 (TGF-[beta]1) induced model of myofibroblast differentiation was used to test the effect of conditioned media from adipose tissue, ADSC or lipid on the proportion of fibroblasts and myofibroblasts. Results Adipose tissue conditioned media inhibited the differentiation of fibroblasts to myofibroblasts but this inhibition was not observed following treatment with ADSC or lipid conditioned media. Hepatocyte growth factor (HGF) was readily detected in the conditioned medium from adipose tissue but not ADSC. Cells treated with HGF, or fortinib to block HGF, demonstrated that HGF was not responsible for the inhibition of myofibroblast differentiation. Conditioned media from adipose tissue was shown to reduce the proportion of myofibroblasts when added to fibroblasts previously treated with TGF-[beta]1, however, conditioned media treatment was unable to significantly reduce the proportion of myofibroblasts in cell populations isolated from scar tissue. Conclusions Cultured ADSC or adipocytes have been the focus of most studies, however, this work highlights the importance of considering whole adipose tissue to further our understanding of fat grafting. This study supports the use of autologous fat grafts for scar treatment and highlights the need for further investigation to determine the mechanism. Keywords: Scarring, Autologous fat grafting, Myofibroblasts, Transforming growth factor [beta]-1, Adipose-derived stromal cells</abstract><pub>BioMed Central Ltd</pub><doi>10.1186/s13287-024-03776-3</doi></addata></record>
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subjects Adipose tissues
Bone morphogenetic proteins
Care and treatment
Ethylenediaminetetraacetic acid
Genetic aspects
Pharmaceutical industry
Scientific equipment and supplies industry
Transforming growth factors
Wounds and injuries
title Inhibition and reversal of a TGF-[beta]1 induced myofibroblast phenotype by adipose tissue-derived paracrine factors
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