Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy

The pathogenesis and progression of knee inflammatory pathologies is modulated partly by residing macrophages in the infrapatellar fat pad (IFP), thus, macrophage polarization towards pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes is important in joint disease pathologies. Alteration of...

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Autores principales:	Dimitrios Kouroupis, Thomas M. Best, Lee D. Kaplan, Diego Correa, Anthony J. Griswold
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	infrapatellar fat pad single-cell RNA-sequencing macrophages mesenchymal stem cells inflammation Technology T Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/60532b6d912643d780cab4f5f6871be3
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spelling	oai:doaj.org-article:60532b6d912643d780cab4f5f6871be32021-11-25T16:46:29ZSingle-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy10.3390/bioengineering81101662306-5354https://doaj.org/article/60532b6d912643d780cab4f5f6871be32021-10-01T00:00:00Zhttps://www.mdpi.com/2306-5354/8/11/166https://doaj.org/toc/2306-5354The pathogenesis and progression of knee inflammatory pathologies is modulated partly by residing macrophages in the infrapatellar fat pad (IFP), thus, macrophage polarization towards pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes is important in joint disease pathologies. Alteration of M1/M2 balance contributes to the initiation and progression of joint inflammation and can be potentially altered with mesenchymal stem cell (MSC) therapy. In an acute synovial/IFP inflammation rat model a single intra-articular injection of IFP-MSC was performed, having as controls (1) diseased rats not receiving IFP-MSC and (2) non-diseased rats. After 4 days, cell specific transcriptional profiling via single-cell RNA-sequencing was performed on isolated IFP tissue from each group. Eight transcriptomically distinct cell populations were identified within the IFP across all three treatment groups with a noted difference in the proportion of myeloid cells across the groups. Largely myeloid cells consisted of macrophages (>90%); one M1 sub-cluster highly expressing pro-inflammatory markers and two M2 sub-clusters with one of them expressing higher levels of canonical M2 markers. Notably, the diseased samples (11.9%) had the lowest proportion of cells expressing M2 markers relative to healthy (14.8%) and MSC treated (19.4%) samples. These results suggest a phenotypic polarization of IFP macrophages towards the pro-inflammatory M1 phenotype in an acute model of inflammation, which are alleviated by IFP-MSC therapy inducing a switch towards an alternate M2 status. Understanding the IFP cellular heterogeneity and associated transcriptional programs may offer insights into novel therapeutic strategies for disabling joint disease pathologies.Dimitrios KouroupisThomas M. BestLee D. KaplanDiego CorreaAnthony J. GriswoldMDPI AGarticleinfrapatellar fat padsingle-cell RNA-sequencingmacrophagesmesenchymal stem cellsinflammationTechnologyTBiology (General)QH301-705.5ENBioengineering, Vol 8, Iss 166, p 166 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	infrapatellar fat pad single-cell RNA-sequencing macrophages mesenchymal stem cells inflammation Technology T Biology (General) QH301-705.5
spellingShingle	infrapatellar fat pad single-cell RNA-sequencing macrophages mesenchymal stem cells inflammation Technology T Biology (General) QH301-705.5 Dimitrios Kouroupis Thomas M. Best Lee D. Kaplan Diego Correa Anthony J. Griswold Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy
description	The pathogenesis and progression of knee inflammatory pathologies is modulated partly by residing macrophages in the infrapatellar fat pad (IFP), thus, macrophage polarization towards pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes is important in joint disease pathologies. Alteration of M1/M2 balance contributes to the initiation and progression of joint inflammation and can be potentially altered with mesenchymal stem cell (MSC) therapy. In an acute synovial/IFP inflammation rat model a single intra-articular injection of IFP-MSC was performed, having as controls (1) diseased rats not receiving IFP-MSC and (2) non-diseased rats. After 4 days, cell specific transcriptional profiling via single-cell RNA-sequencing was performed on isolated IFP tissue from each group. Eight transcriptomically distinct cell populations were identified within the IFP across all three treatment groups with a noted difference in the proportion of myeloid cells across the groups. Largely myeloid cells consisted of macrophages (>90%); one M1 sub-cluster highly expressing pro-inflammatory markers and two M2 sub-clusters with one of them expressing higher levels of canonical M2 markers. Notably, the diseased samples (11.9%) had the lowest proportion of cells expressing M2 markers relative to healthy (14.8%) and MSC treated (19.4%) samples. These results suggest a phenotypic polarization of IFP macrophages towards the pro-inflammatory M1 phenotype in an acute model of inflammation, which are alleviated by IFP-MSC therapy inducing a switch towards an alternate M2 status. Understanding the IFP cellular heterogeneity and associated transcriptional programs may offer insights into novel therapeutic strategies for disabling joint disease pathologies.
format	article
author	Dimitrios Kouroupis Thomas M. Best Lee D. Kaplan Diego Correa Anthony J. Griswold
author_facet	Dimitrios Kouroupis Thomas M. Best Lee D. Kaplan Diego Correa Anthony J. Griswold
author_sort	Dimitrios Kouroupis
title	Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy
title_short	Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy
title_full	Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy
title_fullStr	Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy
title_full_unstemmed	Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy
title_sort	single-cell rna-sequencing identifies infrapatellar fat pad macrophage polarization in acute synovitis/fat pad fibrosis and cell therapy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/60532b6d912643d780cab4f5f6871be3
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Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy

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