{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:57:10Z","timestamp":1793307430748,"version":"4.5.0"},"reference-count":90,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>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 (&gt;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.<\/jats:p>","DOI":"10.3390\/bioengineering8110166","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T11:47:38Z","timestamp":1635767258000},"page":"166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis\/Fat Pad Fibrosis and Cell Therapy"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3892-9013","authenticated-orcid":false,"given":"Dimitrios","family":"Kouroupis","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, UHealth Sports Medicine Institute, University of Miami, Miller School of Medicine, Miami, FL 33146, USA"},{"name":"Diabetes Research Institute and Cell Transplant Center, University of Miami, Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Best","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, UHealth Sports Medicine Institute, University of Miami, Miller School of Medicine, Miami, FL 33146, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee D.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, UHealth Sports Medicine Institute, University of Miami, Miller School of Medicine, Miami, FL 33146, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Correa","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, UHealth Sports Medicine Institute, University of Miami, Miller School of Medicine, Miami, FL 33146, USA"},{"name":"Diabetes Research Institute and Cell Transplant Center, University of Miami, Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Griswold","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA"},{"name":"The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/joa.12820","article-title":"The infrapatellar fat pad and the synovial membrane: An anatomo-functional unit","volume":"233","author":"Macchi","year":"2018","journal-title":"J. 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