{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:42:14Z","timestamp":1784547734357,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009326","name":"Cancer Research Society","doi-asserted-by":"publisher","award":["OG834469"],"award-info":[{"award-number":["OG834469"]}],"id":[{"id":"10.13039\/100009326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009326","name":"Cancer Research Society","doi-asserted-by":"publisher","award":["RB002743"],"award-info":[{"award-number":["RB002743"]}],"id":[{"id":"10.13039\/100009326","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Centers for Regenerative Therapy","award":["OG834469"],"award-info":[{"award-number":["OG834469"]}]},{"name":"Canadian Centers for Regenerative Therapy","award":["RB002743"],"award-info":[{"award-number":["RB002743"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mesenchymal stromal cells (MSCs) are largely known for their immune-suppressive capacity, hence, their common use in the control of unwanted inflammation. However, novel concepts related to their biology, combined with the urgent need to identify MSC subpopulations with enhanced suppressive properties, drive the search for isolation protocols optimized for clinical applications. We show, in this study, that MSCs expressing high CD146 levels exhibit altered surface expression profiles of CD44 and secrete elevated levels of interleukin (IL)-6, amongst other factors. In addition, CD146hi MSCs surpass the polyclonal parental populations in inhibiting alloreactive T cells in vitro, in both a soluble- and cell-contact-dependent manner. Despite the lack of CD146hi MSC-mediated activation of peritoneal macrophages to release the suppressive factor IL-10 in vitro, their administration in animals with graft-versus-host disease alleviates inflammation and leads to 40% survival rate up to 7 weeks post-transplantation. This pronounced inhibitory property is driven by CD146-mediated in situ efferocytosis by myeloid cells. Altogether, this study provides the impetus to adopt an isolation protocol for MSCs based on a CD146 expression profile before their therapeutic use and suggests a major role played by CD146 as a novel \u201ceat-me\u201d signal, capable of enhancing MSC uptake by competent phagocytes.<\/jats:p>","DOI":"10.3390\/cells11152263","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T03:58:44Z","timestamp":1658462324000},"page":"2263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["CD146 Defines a Mesenchymal Stromal Cell Subpopulation with Enhanced Suppressive Properties"],"prefix":"10.3390","volume":"11","author":[{"given":"Jean-Pierre","family":"Bikorimana","sequence":"first","affiliation":[{"name":"Department of Microbiology, Infectious Diseases and Immunology, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4322-1930","authenticated-orcid":false,"given":"Wael","family":"Saad","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4353-5585","authenticated-orcid":false,"given":"Jamilah","family":"Abusarah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malak","family":"Lahrichi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Talbot","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riam","family":"Shammaa","sequence":"additional","affiliation":[{"name":"Canadian Centers for Regenerative Therapy, Toronto, ON M5R 1A8, Canada"},{"name":"IntelliStem Technologies Inc., Toronto, ON M5R 3N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4457-1350","authenticated-orcid":false,"given":"Moutih","family":"Rafei","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Infectious Diseases and Immunology, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"},{"name":"Department of Pharmacology and Physiology, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"},{"name":"Molecular Biology Program, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/bjh.12545","article-title":"Multiple infusions of mesenchymal stromal cells induce sustained remission in children with steroid-refractory, grade III-IV acute graft-versus-host disease","volume":"163","author":"Ball","year":"2013","journal-title":"Br. 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