title: Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increases in TNF-stimulated gene 6.
abstract: BACKGROUND
  Implantation of mesenchymal stem cells (MSCs) has recently been reported to repair tissue injuries through anti-inflammatory and immunosuppressive effects. We established dedifferentiated fat (DFAT) cells that show identical characteristics to MSCs.
  
  
  METHODS
  We examined the effects of 10(6) of DFAT cells infused through renal artery or tail vein on monoclonal antibody (mAb) 1-22-3-induced glomerulonephritis (as an immunological type of renal injury) and adriamycin-induced nephropathy (as a non-immunological type of renal injury) in rats. The mAb 1-22-3-injected rats were also implanted with 10(6) of DFAT cells transfected with TSG-6 siRNA through tail vein.
  
  
  RESULTS
  Although DFAT cells transfused into blood circulation through the tail vein were trapped mainly in lungs without reaching the kidneys, implantation of DFAT cells reduced proteinuria and improved glomerulosclerosis and interstitial fibrosis. Implantation of DFAT cells through the tail vein significantly decreased expression of kidney injury molecule-1, collagen IV and fibronectin mRNAs, whereas nephrin mRNA expression was increased. Implantation of DFAT cells did not improve adriamycin-induced nephropathy, but significantly decreased the glomerular influx of macrophages, common leukocytes and pan T cells. However, the glomerular influx of helper T cells, was increased. Implantation of DFAT cells decreased expression of interleukin (IL)-6 and IL-12β mRNAs and increased expression of TNF-stimulated gene (TSG)-6 mRNA in renal cortex from mAb 1-22-3-injected rats. The basal level of TSG-6 protein was significantly higher in DFAT cells than in fibroblasts. Expression of TSG-6 mRNA in MCs cocultured with DFAT cells was significantly higher than in mesangial cells or DFAT cells alone. Systematic implantation of DFAT cells with TSG-6 siRNA through tail vein did not improve proteinuria, renal dysfunction and renal degeneration in the mAb 1-22-3-injected rats.
  
  
  CONCLUSIONS
  Systematic implantation of DFAT cells effectively ameliorated mAb 1-22-3-induced glomerulonephritis through immunosuppressive effects accompanied by the suppression of macrophage infiltration and expression of IL-6, IL-10 and IL-12β, and increased production of serum and renal TSG-6 that improved the mAb 1-22-3-induced renal degeneration by the immunosuppressive effects of TSG-6. Thus DFAT cells will be suitable cell source for the treatment of immunological progressive renal diseases.
authors.affiliation: Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. maruyama.takashi@nihon-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. fukuda.noboru@nihon-u.ac.jp.|Advanced Research Institute of the Sciences and Humanities, Nihon University Graduate School, Tokyo, Japan. fukuda.noboru@nihon-u.ac.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.affiliation: Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan. matsumoto.taro@nihon-u.ac.jp.
authors.forename: Taro
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Laboratory of Cell and Tissue Biology, College of Bioresource Science, Nihon University, Fujisawa, Japan. kano.kouichirou@nihon-u.ac.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kano
authors.affiliation: Faculty of Human Health Science, Hachinohe Gakuin University, Hachinohe, Aomori, Japan. mendo@htv-net.ne.jp.
authors.forename: Morito
authors.initials: M
authors.lastname: Endo
authors.affiliation: Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan. fwnz2459@mb.infoweb.ne.jp.
authors.forename: Minako
authors.initials: M
authors.lastname: Kazama
authors.affiliation: Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan. kazama.tomohiko@nihon-u.ac.jp.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kazama
authors.affiliation: Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. septembre.99@gmail.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Ikeda
authors.affiliation: Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. hiroyuki.matsuda@med.nihon-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsuda
authors.affiliation: Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. ueno.takahiro@nihon-u.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. abe.masanori@nihon-u.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
authors.affiliation: Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. okada.kazuyoshi@nihon-u.ac.jp.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Okada
authors.affiliation: Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. souma.masayoshi@nihon-u.ac.jp.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.affiliation: Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. matsumoto.koichi91@nihon-u.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. kawachi@med.niigata-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054337:Cell Dedifferentiation; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005921:Glomerulonephritis / Q000209:etiology* / Q000628:therapy; D007165:Immunosuppression Therapy; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009393:Nephritis / Q000139:chemically induced / Q000628:therapy; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016207:Cytokines; C513056:Tnfaip6 protein, rat