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Titolo:
Genetically modified bone marrow continuously supplies anti-inflammatory cells and suppresses renal injury in mouse Goodpasture syndrome
Autore:
Yokoo, T; Ohashi, T; Utsunomiya, Y; Shen, JS; Hisada, Y; Eto, Y; Kawamura, T; Hosoya, T;
Indirizzi:
Jikei Univ, Sch Med, Dept Internal Med 2, Minato Ku, Tokyo 1058641, Japan Jikei Univ Tokyo Japan 1058641 al Med 2, Minato Ku, Tokyo 1058641, Japan Jikei Univ, Sch Med, Dept Gene Therapy, Tokyo 1058641, Japan Jikei Univ Tokyo Japan 1058641 , Dept Gene Therapy, Tokyo 1058641, Japan Jikei Univ, Sch Med, Inst DNA Med, Tokyo 1058641, Japan Jikei Univ TokyoJapan 1058641 h Med, Inst DNA Med, Tokyo 1058641, Japan Jikei Univ, Sch Med, Dept Pediat, Tokyo 1058641, Japan Jikei Univ Tokyo Japan 1058641 ch Med, Dept Pediat, Tokyo 1058641, Japan Tanabe Seiyaku Co Ltd, Discovery Res Lab, Osaka, Japan Tanabe Seiyaku Co Ltd Osaka Japan Ltd, Discovery Res Lab, Osaka, Japan
Titolo Testata:
BLOOD
fascicolo: 1, volume: 98, anno: 2001,
pagine: 57 - 64
SICI:
0006-4971(20010701)98:1<57:GMBMCS>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTERLEUKIN-1 RECEPTOR ANTAGONIST; HEMATOPOIETIC STEM-CELLS; MEDIATED GENE-TRANSFER; HIGH-EXPRESSION; VEHICLE CELLS; IN-VIVO; TRANSPLANTATION; MICE; THERAPY; MACROPHAGES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Yokoo, T Jikei Univ, Sch Med, Dept Internal Med 2, Minato Ku, 3-25-8 NishiShimbashi, Tokyo 1058641, Japan Jikei Univ 3-25-8 Nishi Shimbashi Tokyo Japan 1058641 641, Japan
Citazione:
T. Yokoo et al., "Genetically modified bone marrow continuously supplies anti-inflammatory cells and suppresses renal injury in mouse Goodpasture syndrome", BLOOD, 98(1), 2001, pp. 57-64

Abstract

In chronic inflammation, macrophages and neutrophils, which are derived from bone marrow, play a pivotal role. Therefore, reconstitution of bone marrow With anti-inflammatory stem cells may modify inflammation. In this study, transplantation-based gene therapy was applied to glomerular inflammationfor a long-lasting suppression of the glomerular damage seen in chronic nephritis, Bone marrow cells were harvested from male donor mice, which had received 5-fluorouracil 3 days previously, and transduced with an interleukin 1 (IL-1) receptor antagonist (IL-1Ra) or a mock gene using a retrovirus vector. After confirmation that transduced cells possessed the transgene at approximately 0.7 copies per cell and secreted recombinant IL-1Ra, these cells were infused into sublethally irradiated (6 Gy) female recipients once daily for 4 consecutive days. These female recipient mice had the male Y antigen in bone marrow, liver, and spleen, and 10% to 20% of their spleen cells possessed the transgene even 8 weeks after transplantation. Glomerulonephritis was then induced in these mice. Renal function and histology were retarded in the mice whose bone marrow was reconstituted with IL-1Ra-producing cells compared with mock transduced cells. In situ hybridization using a Y painting probe revealed that transplanted donor cells were recruited intothe glomerulus upon induction of nephritis, suggesting therapeutic effectswere channeled through the secretion of IL-1Ra from these cells. Furthermore, the survival rate after a second challenge with nephrotoxic antibody was significantly improved in the IL-1Ra chimera. These results suggest that reconstitution of bone marrow for continuous supply of anti-inflammatory cells may be a useful strategy for the treatment of chronic inflammation. (C)2001 by The American Society of Hematology.

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Documento generato il 15/07/20 alle ore 08:26:46