RT Journal Article
T1 Human embryonic stem cell-derived mesenchymal stromal cells ameliorate collagen-induced arthritis by inducing host-derived indoleamine 2,3 dioxygenase
A1 Gonzalo-Gil, Elena
A1 Pérez-Lorenzo, María José
A1 Galindo Izquierdo, María
A1 Díaz de la Guardia, Rafael
A1 López-Millán, Belén
A1 Bueno, Clara
A1 Pablos Álvarez, José Luis
A1 Criado, Gabriel
AB Background: 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.Conclusion: Treatment with hESC-MSC ameliorates CIA by inducing IFNγ(+) Th1 cells and IDO1 in the host. Thus, hESC-MSC can provide an infinite cellular source for treatment of rheumatoid arthritis.
PB Springer Science and Business Media LLC
SN 1478-6362
YR 2016
FD 2016
LK https://hdl.handle.net/20.500.14352/114195
UL https://hdl.handle.net/20.500.14352/114195
LA eng
NO Gonzalo-Gil E, Pérez-Lorenzo MJ, Galindo M, Díaz de la Guardia R, López-Millán B, Bueno C, Menéndez P, Pablos JL, Criado G. 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.
NO Spanish Ministry of Economy and Competitiveness (ISCIII/FEDER PI11/00028 to GC, PI14/01119 to CB, SAF2013- 43065R to PM, RETICS RD12/009 RIER
NO Miguel Servet Fellowships to CB (CP13/00011)
NO Miguel Servet Fellowships to GC (CP13/00014)
NO PM also acknowledges the financial support from the Obra Social La Caixa-Fundació Josep Carreras and the Generalitat de Catalunya (SGR330).
DS Docta Complutense
RD 31 dic 2025