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Immunosuppressive properties have been attributed to mesenchymal stem cells (MSCs) that regulate the phenotype and function of different immune cells. However, such properties were poorly considered until now for adult stem cells with myogenic potential and advanced as possible therapeutic candidates for MDs. In the present study, we investigated the immunoregulatory potential of human MuStem (hMuStem) cells, for which we previously demonstrated that they can survive in injured muscle and robustly counteract adverse tissue remodeling.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The impact of hMuStem cells or their secretome on the proliferative and phenotypic properties of T-cells was explored by co-culture experiments with either peripheral blood mononucleated cells or CD3-sorted T-cells. A comparative study was produced with the bone marrow (BM)-MSCs. The expression profile of immune cell-related markers on hMuStem cells was determined by flow cytometry while their secretory profile was examined by ELISA assays. Finally, the paracrine and cell contact-dependent effects of hMuStem cells on the T-cell-mediated cytotoxic response were analyzed through IFN-\u03b3 expression and lysis activity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Here, we show that hMuStem cells have an immunosuppressive phenotype and can inhibit the proliferation and the cytotoxic response of T-cells as well as promote the generation of regulatory T-cells through direct contact and via soluble factors. These effects are associated, in part, with the production of mediators including heme-oxygenase-1, leukemia inhibitory factor and intracellular cell adhesion molecule-1, all of which are produced at significantly higher levels by hMuStem cells than BM-MSCs. While the production of prostaglandin E2 is involved in the suppression of T-cell proliferation by both hMuStem cells and BM-MSCs, the participation of inducible nitric oxide synthase activity appears to be specific to hMuStem cell-mediated one.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Together, our findings demonstrate that hMuStem cells are potent immunoregulatory cells. Combined with their myogenic potential, the attribution of these properties reinforces the positioning of hMuStem cells as candidate therapeutic agents for the treatment of MDs.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13287-021-02681-3","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T13:03:58Z","timestamp":1641819838000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Human MuStem cells repress T-cell proliferation and cytotoxicity through both paracrine and contact-dependent pathways"],"prefix":"10.1186","volume":"13","author":[{"given":"Marine","family":"Charrier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Lorant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Contreras-Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautier","family":"T\u00e9j\u00e9dor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Blanquart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blandine","family":"Lieubeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Schleder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Leroux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Deshayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Fonteneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candice","family":"Babarit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Hamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armelle","family":"Magot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"P\u00e9r\u00e9on","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Viau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Delorme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Luz-Crawford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Lamirault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farida","family":"Djouad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Rouger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"2681_CR1","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/S0140-6736(02)07815-7","volume":"359","author":"AEH Emery","year":"2002","unstructured":"Emery AEH. 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Patients were free of known muscle disease and had undergone surgery for acute scoliosis at the Department of Pediatric surgery of the Centre Hospitalier Universitaire (CHU) de Nantes (France). Written informed consent was obtained from all patients. All protocols were approved by the Clinical Research Department of the CHU (Nantes, France), according to the rules of the French Regulatory Health Authorities (approval number: MESR\/DC-2010-1199). The biological sample bank was created in compliance with national guidelines regarding the use of human tissue for research (approval number: CPP\/29\/10). Isolation and culture of human bone marrow-derived mesenchymal stem cells: Human BM-MSCs were collected from patients undergoing hip replacement surgery. The patients were informed and provided written informed consent prior to collection of tissue samples as approved by the French Ministry of Higher Education and Research (DC-2010\u20131185).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no financial and non-financial competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7"}}