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Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy
| Content Provider | MDPI |
|---|---|
| Author | Kouroupis, Dimitrios Best, Thomas M. Kaplan, Lee D. Correa, Diego Griswold, Anthony J. |
| Copyright Year | 2021 |
| 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. |
| Starting Page | 166 |
| e-ISSN | 23065354 |
| DOI | 10.3390/bioengineering8110166 |
| Journal | Bioengineering |
| Issue Number | 11 |
| Volume Number | 8 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-10-29 |
| Access Restriction | Open |
| Subject Keyword | Bioengineering Cell Tissue Engineering Pathology Infrapatellar Fat Pad Single-cell Rna-sequencing Macrophages Mesenchymal Stem Cells Inflammation |
| Content Type | Text |
| Resource Type | Article |
