scholarly journals IFN-? stimulated dental follicle mesenchymal stem cells regulate activated lymphocyte response in rheumatoid arthritis patients in vitro

2007 ◽  
Vol 74 (2) ◽  
pp. S217 ◽  
Author(s):  
Tomas Dallos ◽  
Monika Krivosikova ◽  
Lukasz Luszczyna ◽  
Magdalena Chorazy-Massalska ◽  
Ewa Warnawin ◽  
...  

Author(s):  
Deniz Genç ◽  
Merve Sezer Kürkçü ◽  
Gürkan Yiğittürk ◽  
Burcu Günaydın ◽  
Hülya Elbe ◽  
...  

Objectives: In this study, we aimed to investigate the differentiation potential of dental follicle mesenchymal stem cells (MSCs) in the synovial fluid (SF) niche of early-onset or end-stage rheumatoid arthritis (RA). Patients and methods: Between May 2020 and January 2021, six patients (1 male, 5 females; mean age: 57.5±11.2 years; range, 49 to 65 years) who were diagnosed with RA with the indication of SF aspiration were included in the study. The third passage dental follicle stem cells (DFSCs) were cocultured with fresh SF samples of end-stage or early-onset RA patients in micromass culture system for 21 days. SF samples were analyzed for secreted cytokines. Chondrogenic markers (CD49e, CD49f) were analyzed in DFSCs, gene expression analysis was performed for the expressions of Col I, Col II, Aggrecan and Sox-9, and histochemical analysis was performed by staining three-dimensional pellets with anti-collagen II antibody. The neutralization assay was performed with anti-interleukin (IL)-6, anti-interferon-gamma (IFN-g), and anti-IL-1beta(b). Results: The high levels of IL-1b and IL-6 were observed in end-stage RA patients’ SF samples compared to the early-onset patients (p<0.05). The CD49e and CD49f expressions in DFSCs were significantly higher in the SF samples of end-stage RA patients (p<0.05). Also, the Col II, Sox-9 and Aggrecan messenger ribonucleic acid (mRNA) expressions increased in the DFSCs, when cultured with end-stage RA patients’ SF samples (p<0.01). Collagen-II expression in histochemical analysis of micromass pellets was higher in the DFSCs cultured with end-stage RA patients’ SF samples. The neutralization of IL-6 significantly decreased the CD49e and CD49f expressions (p<0.05). Conclusion: The high levels of IL-6 in SF niche of end-stage RA patients were found to differentiate DFSCs toward chondrogenesis. Based on these findings, DFSCs can be used as a new cell-based treatment in RA patients for the cartilage damage.


2012 ◽  
Vol 83 (5) ◽  
pp. 249-259 ◽  
Author(s):  
Bong-Wook Park ◽  
Eun-Ju Kang ◽  
June-Ho Byun ◽  
Myeong-Gyun Son ◽  
Hyun-Joon Kim ◽  
...  

2021 ◽  
Author(s):  
Hyeon-Jeong Lee ◽  
Won-Jae Lee ◽  
Sun-Chul Hwang ◽  
Yong-Ho Choi ◽  
Saetbyul Kim ◽  
...  

Abstract BackgroundAlthough immunomodulation properties of mesenchymal stem cells (MSCs) has been highlighted as a new therapy for autoimmune diseases, including rheumatoid arthritis (RA), the alteration of disease-specific characteristics of MSCs derived from elderly RA patients are not well understood. MethodsWe established the MSCs derived from synovial fluid (SF) from age-matched early (average duration of disease: 1.7 years) and long-standing (average duration of disease: 13.8 years) RA patients (E-/L-SF-MSCs) and then comparatively analyzed the characteristics of MSCs such as stemness, proliferation, cellular senescence, in vitro differentiation and in vivo immunomodulation properties.ResultsThe presence of MSC populations in the SF from RA patients was identified and we found that L-SF-MSCs exhibited impaired proliferation, intensified cellular senescence, reduced immunomodulation properties and attenuation of anti-arthritic capacity in an RA animal model than E-SF-MSCs. In particular, E-SF-MSCs demonstrated cellular senescence progression and attenuation of immunomodulation properties at similar levels to that of L-SF-MSCs in an RA joint mimicking milieu due to hypoxia and pro-inflammatory cytokine exposure. Due to long-term exposure to the chronic inflammation milieu, the progression of cellular senescence, attenuation of immunomodulation properties and loss of anti-arthritic potentials are more often identified in SF-MSCs of long-standing RA than early RA. ConclusionWe conclude that a chronic RA inflammation milieu affected the potential of MSCs; therefore, this work addresses the importance of understanding MSC characteristics during disease states prior to their application in patients.


2008 ◽  
Vol 149 (8) ◽  
pp. 339-346 ◽  
Author(s):  
Judit Kiss ◽  
Veronika Urbán S. ◽  
Valéria Dudics ◽  
Virág Vas ◽  
Ferenc Uher

A mesenchymalis őssejteket (MSC-ket) már számos szövettípusból sikeresen izolálták. Ezek a sejtek terápiás felhasználás szempontjából különösen ígéretesnek tűnnek a felnőtt szöveti őssejtek közül, mivel könnyen izolálhatók, és viszonylag egyszerű a fenntartásuk és szaporításuk in vitro, valamint képesek számos sejttípussá, többek között csont-, porc-, ín-, izom- és zsírsejtekké alakulni. A szervezetben ezek a sejtek biztosítják azokat a növekedési faktorokat és cytokineket, amelyek a vérképző sejtek osztódását és differenciálódását szabályozzák. In vivo képesek lehetnek sérült szövetek regenerálására a vesében, szívben, májban, hasnyálmirigyben és az emésztőrendszerben. Emellett az MSC-k immunmoduláló és gyulladáscsökkentő hatással is rendelkeznek, és allogén szervezetben is csak minimális immunválaszt váltanak ki. Bár a folyamat háttere még nem teljesen ismert, az e sejtek immunszuppresszív hatásán alapuló módszerek már a klinikai kipróbálás fázisában vannak, és lehetséges, hogy a jövőben az MSC-k segítségével allograft-kilökődés, graft versus host betegség, rheumatoid arthritis, autoimmun eredetű ízületi gyulladás és más olyan betegségek lesznek kezelhetők, amelyek esetében immunszuppresszió és szöveti regeneráció is szükséges. A jelen összefoglaló célja a mesenchymalis őssejtekről szóló irodalom áttekintése, különös tekintettel azok immunmoduláló tulajdonságaira és jövőbeli lehetséges klinikai felhasználására.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4486-4486
Author(s):  
Zhenhua Qiao ◽  
Lihui Ma

Abstract Abstract 4486 Objective To explore mechanism of Mesenchymal stem cells in treating Rheumatoid arthritis. Methods (1) MSCs were isolated from Bone marrow samples of Rheumatoid arthritis(RA)patients and purified by density gradient centrifagation and cultured in vitro. Morphology, immunophenotype, and proliferative property of bMSC and colony forming unit-fibroblast (CFU-F) were measured and analyzed. (2) In an in vitro co-culture system, MSCs were observed to modulate proliferation,activation, and maturation of T and B lymphocytes of Rheumatoid arthritis(RA)patients. The expression of IL-1?ATNF-a?ATGF-β were obviously changed.(3) Bone marrow- derived BMSCs of wistar rats were isolated and cultured in vitro routinely and the fourth passage as taken for identification of specific surface antigens by flowcytometry, then were labled with 5- BrdU in vitro. The model of collagen-induced arthritis (CIA) rats were established. 5- BrdU labled BMSCs were implanted through tail vein to model rats. At 4 weeks after BMSCs transplantation, immunohistochemical examinations were used to investigate BMSCs aggregate around the knee joints.and identify the contribution of bone marrow– derived cells to joints damage repair. Results (1) The culture expanded cells from RA patients presented a typical fibroblast-like morphology. Cells were positive for SH2(CD105),CD71,and CD44, but negative for CD45.Their proliferative capacity and CFU-F number were similar to those of bMSCs from healthy donors. (2) MSCs significantly inhibited T,B cell proliferation. MSCs also could down-regulating the levels of IL-1, TNF and up-regulating TGF-β. (3) Flow cytometry showed that BMSCs expressed CD44, CD71and CD105, but no CD45,CD34. At 4 weeks after the cells transplantation, the implanted cells were detected in the damaged joints of the model rats, which is not founded in normal knee joints of the rats'.and at same time there are more OPG(osteoprotegerin) positive. Conclusion (1) In the aspect of morphology, immuno -phenotypen, proliferative property and colony forming unit-fibroblast (CFU-F),MSCs from bone marrow of RA patients are not different from those of MSCs isolated from bone marrow of normal donors,MSCs from the bone marrow of RA patients have the potentiality in clinical application.(2) Human bone marrow MSCs inhibited Tcell and Bcell activation and proliferation in patients with RA in vitro. And these immuno –modulatory effects were not MHC-restricted. (3) bone marrow mesenchymal stem cells prevents tissue damage in arthritis. Allogeneic MSCs can engraft at sites of tissue damage,and prepair damage. That provided positive results for developing effective therapy for Rheumatoid arthritis. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hyeon-Jeong Lee ◽  
Won-Jae Lee ◽  
Sun-Chul Hwang ◽  
Yongho Choe ◽  
Saetbyul Kim ◽  
...  

Abstract Background Although the immunomodulatory properties of mesenchymal stem cells (MSCs) have been highlighted as a new therapy for autoimmune diseases, including rheumatoid arthritis (RA), the disease-specific characteristics of MSCs derived from elderly RA patients are not well understood. Methods We established MSCs derived from synovial fluid (SF) from age-matched early (average duration of the disease: 1.7 years) and long-standing (average duration of the disease: 13.8 years) RA patients (E-/L-SF-MSCs) and then analyzed the MSC characteristics such as stemness, proliferation, cellular senescence, in vitro differentiation, and in vivo immunomodulatory properties. Results The presence of MSC populations in the SF from RA patients was identified. We found that L-SF-MSCs exhibited impaired proliferation, intensified cellular senescence, reduced immunomodulatory properties, and attenuated anti-arthritic capacity in an RA animal model. In particular, E-SF-MSCs demonstrated cellular senescence progression and attenuated immunomodulatory properties similar to those of L-SF-MSC in an RA joint-mimetic milieu due to hypoxia and pro-inflammatory cytokine exposure. Due to a long-term exposure to the chronic inflammatory milieu, cellular senescence, attenuated immunomodulatory properties, and the loss of anti-arthritic potentials were more often identified in SF-MSCs in a long-term RA than early RA. Conclusion We conclude that a chronic RA inflammatory milieu affects the MSC potential. Therefore, this work addresses the importance of understanding MSC characteristics during disease states prior to their application in patients. Graphical abstract


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