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. 2021 Jan 7;12:44. doi: 10.1186/s13287-020-02107-6

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© The Author(s) 2021

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 5 — Immunomodulatory functionality of Crude IFP-MSC spheroids. a CFSE-labeled, PMA/IO-activated human PBMC showed a proliferation of ~ 91.2% for male PBMC donors and of ~ 89.9% for female PBMC donors, which was suppressed in a PBMC gender-dependent manner by co-culture with non-induced Crude or CD146-selected IFP-MSC spheroids (*p < 0.05, n = 3). b In both non-induced and TIC-induced SYN, non-induced Crude IFP-MSC spheroids can effectively form explant-cultures on synoviocyte monolayer whereas TIC induction of SYN significantly (*p < 0.05) upregulates inflammatory genes such as CD13 and PD-1. c SYN/IFP-MSC spheroid co-cultures resulted in significantly (*p < 0.05) higher secretion of immunomodulatory proteins (IL-6, IL-8, IP-10, MCP-1, MCP2, RANTES, TIMP-2) compared to TIC-induced SYN alone. All experiments were performed independently (n = 3)