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In this study, in vitro inflammatory priming to crude human BM-MSCs (n = 8) captured a baseline of signature responses, including enriched CD146+ with coexpression of CD107aHigh, CXCR4High, and LepRHigh, transcriptional profile, enhanced secretory capacity, and robust immunomodulatory secretome and function, including immunopotency assays (IPAs) with stimulated immune cells. These signatures were significantly more pronounced in CD146+ (POS)-sorted subpopulation than in the CD146\u2212 (NEG). Mechanistically, POS BM-MSCs showed a markedly higher secretory capacity with significantly greater immunomodulatory and anti-inflammatory protein production upon inflammatory priming compared with the NEG BM-MSCs. Moreover, IPAs with stimulated peripheral blood mononuclear cells and T lymphocytes demonstrated robust immunosuppression mediated by POS BM-MSC while inducing significant frequencies of regulatory T cells. in vivo evidence showed that POS BM-MSC treatment promoted pronounced M1-to-M2 macrophage polarization, ameliorating inflammation\/fibrosis of knee synovium and fat pad, unlike treatment with NEG BM-MSCs. These data correlate the expression of CD146 with innately higher immunomodulatory and secretory capacity, and thus therapeutic potency. This high-content, reproducible evidence suggests that the CD146+ (POS) MSC subpopulation are the mediators of the beneficial effects achieved using crude BM-MSCs, leading to translational implications for improving cell therapy and manufacturing.<\/jats:p>\n                  <jats:sec>\n                    <jats:title\/>\n                  <\/jats:sec>","DOI":"10.1002\/stem.3196","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T14:55:52Z","timestamp":1588863352000},"page":"1034-1049","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Signature quality attributes of CD146+ mesenchymal stem\/stromal cells correlate with high therapeutic and secretory potency"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1924-8949","authenticated-orcid":false,"given":"Annie C.","family":"Bowles","sequence":"first","affiliation":[{"name":"1 Department of Orthopaedics, UHealth Sports Medicine Institute, University of Miami, Miller School of Medicine, Miami, Florida, USA"},{"name":"2 Diabetes Research Institute & Cell Transplantation Center, University of Miami, Miller School of Medicine, Miami, Florida, USA"},{"name":"3 Department of Biomedical Engineering College of Engineering, University of Miami, Miami, Florida, USA"},{"name":"4 DJTMF Biomedical Nanotechnology Institute at the University of Miami, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Kouroupis","sequence":"additional","affiliation":[{"name":"1 Department of Orthopaedics, UHealth Sports Medicine Institute, University of Miami, Miller School of Medicine, Miami, Florida, USA"},{"name":"2 Diabetes Research Institute & Cell Transplantation Center, University of Miami, Miller School of Medicine, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa 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