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. 2019 Jul 26;9:10864. doi: 10.1038/s41598-019-47391-2

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Rat model of acute synovium/IFP inflammation. Hematoxylin and Eosin staining, human mitochondria (Hu Mit) and rat Substance P (Rat SP) immunolocalization in sagitally-sectioned knees of representative rats injected only with MIA (A), only with IFP-MSC (B), and with both MIA and IFP-MSC (C and D). White arrows help localize the bead chain-like structures of SP-positive nerve fibres between adipocytes inside the IFP as previously described^22,79. Compared with healthy rats (B) where few SP⁺ fibres were observed, MIA-treated rats show increased SP presence both at the periphery and the inner part of the IFP (A). The groups receiving IFP-MSC (C,D), show a dramatic reduction in SP positivity at the periphery of the IFP (close to the synovium), while less pronounced reduction in the inner part. Black arrows help localize engrafted human IFP-MSC, predominantly in synovium and to a lesser extent the IFP after 3 days of injection (C), significantly reduced after 7 days of injection (D). Of note, a small amount of IFP-MSC were localized in a synovial spot in healthy rats (B), while no signal was detected in rats receiving only MIA with no cells (A), supporting the high specificity of the signal. 4X, 20X and 40X objectives generate magnifications of 40, 200 and 400 times. * areas of synovitis; Fib = areas of fibrosis; M = meniscus; IFP = infrapatellar fat pad.