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However, the inability to manufacture large quantities of functional cells from a single donor as well as donor-dependent variability in quality limits their clinical utility. Human embryonic stem cell (hESC)-derived MSCs are an alternative to adult MSCs that can circumvent issues regarding scalability and consistent quality due to their derivation from a renewable starting material. Here, we show that hESC-MSCs prevent the progression of fatal lupus nephritis (LN) in NZB\/W F1 (BWF1) mice. Treatment led to statistically significant reductions in proteinuria and serum creatinine and preserved renal architecture. Specifically, hESC-MSC treatment prevented disease-associated interstitial inflammation, protein cast deposition and infiltration of CD3<jats:sup>+<\/jats:sup> lymphocytes in the kidneys. This therapy also led to significant reductions in serum levels of tumor necrosis factor alpha (TNF\u03b1) and interleukin 6 (IL-6), two inflammatory cytokines associated with SLE. Mechanistically, <jats:italic>in vitro<\/jats:italic> data support these findings, as co-culture of hESC-MSCs with lipopolysaccharide (LPS)-stimulated BWF1 lymphocytes decreased lymphocyte secretion of TNF\u03b1 and IL-6 and enhanced the percentage of putative regulatory T cells. This study represents an important step in the development of a commercially scalable and efficacious cell therapy for SLE\/LN.<\/jats:p>","DOI":"10.1038\/srep17685","type":"journal-article","created":{"date-parts":[[2015,12,2]],"date-time":"2015-12-02T10:12:11Z","timestamp":1449051131000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Human embryonic stem cell-derived mesenchymal cells preserve kidney function and extend lifespan in NZB\/W F1 mouse model of lupus nephritis"],"prefix":"10.1038","volume":"5","author":[{"given":"Austin","family":"Thiel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Yavanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Dorothea","family":"Nastke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Kouris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin A.","family":"Kimbrel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lanza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,12,2]]},"reference":[{"key":"BFsrep17685_CR1","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nrrheum.2013.157","volume":"10","author":"W Xiong","year":"2014","unstructured":"Xiong, W. & Lahita, R. 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