000 nab a22 7a 4500
999 _c17883
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008 240624b xxu||||| |||| 00| 0 eng d
040 _cH12O
041 _aeng
100 _91945
_aGonzalo Gil, Elena
_eReumatología
100 _92652
_aPérez Lorenzo, María J.
_eInstituto de Investigación i+12
100 _9466
_aGalindo Izquierdo, María
_eReumatología
100 _91010
_aPablos Álvarez, José Luis
_eReumatología
100 _91880
_aCriado Carrasco, Gabriel
_eInstituto de Investigación i+12
245 0 0 _aHuman embryonic stem cell-derived mesenchymal stromal cells ameliorate collagen-induced arthritis by inducing host-derived indoleamine 2,3 dioxygenase.
_h[artículo]
260 _bArthritis research and therapy,
_c2016
300 _a18:77.
500 _aFormato Vancouver: Gonzalo Gil E, Pérez Lorenzo MJ, Galindo M, Díaz de la Guardia R, López Millán B, Bueno C et al. Human embryonic stem cell-derived mesenchymal stromal cells ameliorate collagen-induced arthritis by inducing host-derived indoleamine 2,3 dioxygenase. Arthritis Res Ther. 2016 Apr 1;18:77.
501 _aPMID: 27036118 PMC4818397
504 _aContiene 48 referencias
520 _aBackground: The immunosuppressive and anti-inflammatory properties of mesenchymal stromal cells (MSC) have prompted their therapeutic application in several autoimmune diseases, including rheumatoid arthritis. Adult MSC are finite and their clinical use is restricted by the need for long-term expansion protocols that can lead to genomic instability. Inhibition of Smad2/3 signaling in human pluripotent stem cells (hPSC) provides an infinite source of MSC that match the phenotype and functional properties of adult MSC. Here, we test the therapeutic potential of hPSC-MSC of embryonic origin (embryonic stem cell-derived mesenchymal stromal cells, hESC-MSC) in the experimental model of collagen-induced arthritis (CIA). Methods: CIA was induced in DBA/1 mice by immunization with type II collagen (CII) in Complete Freund's Adjuvant (CFA). Mice were treated with either a single dose (10(6) cells/mouse) of hESC-MSC on the day of immunization (prophylaxis) or with three doses of hESC-MSC every other day starting on the day of arthritis onset (therapy). Arthritis severity was evaluated daily for six weeks and ten days, respectively. Frequency of Treg (FoxP3(+)), Th1 (IFNγ(+)) and Th17 (IL17(+)) CD4(+) T cells in inguinal lymph nodes (ILN) was quantified by flow cytometry. Serum levels of anti-CII antibodies were determined by ELISA. Detection of hESC-MSC and quantification of murine and human indoleamine 2,3 dioxygenase (IDO1) expression was performed by quantitative real-time PCR. Statistical differences were analyzed by ANOVA and the Mann-Whitney U test. Results: Administration of hESC-MSC to mice with established arthritis reduced disease severity compared to control-treated mice. Analysis of CD4 T cell populations in treated mice showed an increase in FoxP3(+) Treg and IFNγ(+) Th1 cells but not in Th17 cells in the ILN. Anti-CII antibody levels were not affected by treatment. Migration of hESC-MSC to the ILN in treated mice was associated with the induction of murine IDO1.
710 _9625
_aInstituto de Investigación imas12
710 _9123
_aServicio de Reumatología
856 _uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818397/
_yAcceso libre
942 _2ddc
_cART
_n0