{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:06:07Z","timestamp":1792109167834,"version":"4.4.0"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T00:00:00Z","timestamp":1672012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SMART II National Medical Research Council (NMRC) Centre","award":["NMRC\/CG\/M011\/2017_SGH"],"award-info":[{"award-number":["NMRC\/CG\/M011\/2017_SGH"]}]},{"DOI":"10.13039\/501100004327","name":"SingHealth Foundation","doi-asserted-by":"crossref","award":["SHF\/FG638P\/2016"],"award-info":[{"award-number":["SHF\/FG638P\/2016"]}],"id":[{"id":"10.13039\/501100004327","id-type":"DOI","asserted-by":"crossref"}]},{"name":"SRG","award":["SRG-APP-OPN05"],"award-info":[{"award-number":["SRG-APP-OPN05"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>To determine the therapeutic efficacy of human umbilical cord lining mesenchymal stromal cells (CL-MSCs) (US Patent number 9,737,568) in lupus-prone MRL\/lpr (Faslpr) mice and elucidate its working mechanisms. A total of 4 doses of (20\u201325) \u00d7 106 cells\/kg of CL-MSCs was given to 16-week-old female Faslpr mice by intraperitoneal injection. Three subsequent doses were given on 17 weeks, 18 weeks, and 22 weeks, respectively. Six-week-old Faslpr mice were used as disease pre-onset controls. Mice were monitored for 10 weeks. Mouse kidney function was evaluated by examining complement component 3 (C3) deposition, urinary albumin-to-creatinine ratio (ACR), and lupus nephritis (LN) activity and chronicity. Working mechanisms were elucidated by flow cytometry, Luminex\/ELISA (detection of anti-dsDNA and isotype antibodies), and RNA sequencing. CL-MSCs improved mice survival and kidney function by reducing LN activity and chronicity and lymphocyte infiltration over 10 weeks. CL-MSCs also reduced urinary ACR, renal complement C3 deposition, anti-dsDNA, and isotype antibodies that include IgA, IgG1, IgG2a, IgG2b, and IgM. Immune and cytokine profiling demonstrated that CL-MSCs dampened inflammation by suppressing splenic neutrophils and monocytes\/macrophages, reducing plasma IL-6, IL-12, and CXCL1 and stabilizing plasma interferon-\u03b3 and TNF-\u03b1. RNA sequencing further showed that CL-MSCs mediated immunomodulation via concerted action of pro-proinflammatory cytokine-induced chemokines and production of nitric oxide in macrophages. CL-MSCs may provide a novel myeloid (neutrophils and monocytes\/macrophages)-targeting therapy for SLE.<\/jats:p>","DOI":"10.3390\/ijms24010365","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T04:42:47Z","timestamp":1672116167000},"page":"365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Intraperitoneally Delivered Umbilical Cord Lining Mesenchymal Stromal Cells Improve Survival and Kidney Function in Murine Lupus via Myeloid Pathway Targeting"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7894-9695","authenticated-orcid":false,"given":"Alvin Wen Choong","family":"Chua","sequence":"first","affiliation":[{"name":"Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianyang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Clinical Translational Research, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia Chi","family":"Tan","sequence":"additional","affiliation":[{"name":"Single-Cell Computational Immunology, Singapore Immunology Network, Singapore 138668, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances Ting Wei","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Clinical Translational Research, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chee Tian","family":"Ong","sequence":"additional","affiliation":[{"name":"CellResearch Corporation Pte Ltd., Singapore 048943, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeyakumar","family":"Masilamani","sequence":"additional","affiliation":[{"name":"CellResearch Corporation Pte Ltd., Singapore 048943, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony Kiat Hon","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Singapore General Hospital, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0143-6263","authenticated-orcid":false,"given":"William Ying Khee","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Singapore General Hospital, Singapore 169856, Singapore"},{"name":"National Cancer Centre Singapore, Singapore 169610, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivor Jiun","family":"Lim","sequence":"additional","affiliation":[{"name":"CellResearch Corporation Pte Ltd., Singapore 048943, Singapore"},{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Single-Cell Computational Immunology, Singapore Immunology Network, Singapore 138668, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toan Thang","family":"Phan","sequence":"additional","affiliation":[{"name":"CellResearch Corporation Pte Ltd., Singapore 048943, Singapore"},{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9479-6913","authenticated-orcid":false,"given":"Xiubo","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Clinical Translational Research, Singapore General Hospital, Singapore 169608, Singapore"},{"name":"SingHealth Duke-NUS Medicine Academic Clinical Programme, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/s41590-020-0743-0","article-title":"Mapping systemic lupus erythematosus heterogeneity at the single-cell level","volume":"21","author":"Hong","year":"2020","journal-title":"Nat. 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