Serum-starved adipose-derived stromal cells ameliorate crescentic GN by promoting immunoregulatory macrophages

Kazuhiro Furuhashi, Naotake Tsuboi, Asuka Shimizu, Takayuki Katsuno, Hangsoo Kim, Yosuke Saka, Takenori Ozaki, Yoshikazu Sado, Enyu Imai, Seiichi Matsuo, Shoichi Maruyama

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Mesenchymal stromal cells (MSCs) derived from adipose tissue have immunomodulatory effects, suggesting that they may have therapeutic potential for crescentic GN. Here, we systemically administered adipose-derived stromal cells (ASCs) in a rat model of anti-glomerular basement membrane (anti-GBM) disease and found that this treatment protected against renal injury and decreased proteinuria, crescent formation, and infiltration by glomerular leukocytes, including neutrophils, CD8+ T cells, and CD68+ macrophages. Interestingly, ASCs cultured under low-serum conditions (LASCs), but not bone marrow-derived MSCs (BM-MSCs), increased the number of immunoregulatory CD163+ macrophages in diseased glomeruli. Macrophages cocultured with ASCs, but not with BM-MSCs, adopted an immunoregulatory phenotype. Notably, LASCs polarized macrophages into CD163 + immunoregulatory cells associated with IL-10 production more efficiently than ASCs cultured under high-serum conditions. Pharmaceutical ablation of PGE2 production, blocking the EP4 receptor, or neutralizing IL-6 in the coculture medium all significantly reversed this LASC-induced conversion of macrophages. Furthermore, pretreating LASCs with aspirin or cyclooxygenase-2 inhibitors impaired the ability of LASCs toameliorate nephritogenic IgG-mediated renal injury. Taken together, these results suggest thatLASCs exert renoprotective effects in anti-GBM GN by promoting the phenotypic conversion of macrophages to immunoregulatory cells, suggesting that LASCtransfermay represent a therapeutic strategy for crescentic GN.

Original languageEnglish
Pages (from-to)587-603
Number of pages17
JournalJournal of the American Society of Nephrology
Volume24
Issue number4
DOIs
Publication statusPublished - 29-03-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Nephrology

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