CoChat
Sign Up
Cited by 109Mesenchymal stem cell researchRheumatoid Arthritis Research and TherapiesOsteoarthritis Treatment and Mechanisms

The Secretome Derived From 3D-Cultured Umbilical Cord Tissue MSCs Counteracts Manifestations Typifying Rheumatoid Arthritis

Open access
Miranda, Joana P., Camões, Sérgio P., Gaspar, Maria M., Rodrigues, Joana S., Carvalheiro, Manuela, Bárcia, Rita N., Cruz, Pedro, Cruz, Helder +2 more·2019·Frontiers in Immunology
DOI 10.3389/fimmu.2019.00018PMC PMC6370626
Open this paper in CoChat — free accountOpen PDF

Abstract

Rheumatoid arthritis (RA) is an autoimmune disorder whose treatment is mostly restricted to pain and symptom management and to the delay of joint destruction. Mesenchymal stem/stromal cells from the umbilical cord tissue (UC-MSCs) have previously been proven to be immunomodulatory and more efficient than bone marrow-derived MSCs in causing remission of local and systemic arthritic manifestations in vivo. Given the paracrine nature of UC-MSC activity, their application as active substances can be replaced by their secretome, thus avoiding allogeneic rejection and safety issues related to unwanted grafting. In this work, we aimed at demonstrating the viability of applying the 3D-primed UC-MSC secretome for the amelioration of arthritic signs. A proteomics analysis was performed to both, media conditioned by UC-MSC monolayer (CM2D) and 3D cultures (CM3D). The analysis of relevant trophic factors confirmed secretome profiles with very significant differences in terms of therapeutic potential. Whereas CM3D was characterized by a prevailing expression of anti-inflammatory cytokines such as IL-10 and LIF, along with trophic factors involved in different mechanisms leading to tissue regeneration, such as PDGF-BB, FGF-2, I-309, SCF and GM-CSF; CM2D presented relatively higher levels of IL-6, MCP-1 and IL-21, with recognized pro-inflammatory roles in joint disease and pleiotropic effects in the progression of rheumatoid arthritis (RA). Accordingly, different motogenic effects over mouse chondrocytes and distinct capacities of inducing glycosaminoglycan synthesis in vitro were observed between CM3D and CM2D. Finally, the evaluation of arthritic manifestations in vivo, using an adjuvant-induced model for arthritis (AIA), suggested a significantly higher therapeutic potential of CM3D over CM2D and even UC-MSCs. Histological analysis confirmed a faster remission of local and systemic arthritic manifestations of CM3D-treated animals. Overall, the results show that the use of UC-MSC CM3D is a viable and better strategy than direct UC-MSC administration for counteracting AIA-related signs. This strategy represents a novel MSC-based but nonetheless cell-free treatment for arthritic conditions such as those characterizing RA.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fimmu.2019.00018

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • These results indicate that fibroblast-mediated extracellular matrix, angiogenesis and vasculogenesis, processes implicated in wound healing, are improved by 3D culture-preconditioning strategies.

    “These results indicated that fibroblast-mediated ECM, angiogenesis and vasculogenesis, processes implicated in the wound healing process, are indeed improved by 3D culture-preconditioning strategies [8].”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [8]

    The Results report that 3D-cultured UC-MSCs produced a different secretome from 2D-cultured cells, and the Discussion identifies factors in that secretome associated with angiogenesis. The paper does not show that 3D preconditioning improves fibroblast-mediated ECM production, angiogenesis, or vasculogenesis in wound healing; its measured functional outcomes concern chondrocytes and inflammatory arthritis. Page numbers are unavailable in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The secretome derived from UC-MSC spheroids has higher levels of FGF-2, G-CSF, HGF, IL-6 and TGF-β1 compared to two-dimensional conditioned media.

    “we have also previously shown that the secretome derived from UC-MSC spheroids has higher levels of FGF-2, G-CSF, HGF, IL-6 and TGF-β1, when compared to two-dimensional conditioned media (CM2D).”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [8]

    The Results section on trophic factors (page unavailable) identifies FGF-2 as more prominent in CM3D, and the Discussion lists G-CSF among factors produced in CM3D. But both sections say IL-6 is higher in CM2D, contrary to the claim; the passages do not establish higher HGF or TGF-β1 in CM3D. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • MSCs empower resident cells through the secretion of trophic factors, inducing those cells to regenerate damaged tissue.

    “MSCs were shown to empower the resident cells through the secretion of trophic factors, inducing those cells to regenerate the damaged tissue [7], [8], [9], [10].”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [8]

  • Culturing MSCs in 3D culture systems mimics the complexity of physiological conditions by allowing better cell-to-cell and cell-to-extracellular matrix interactions.

    “Another strategy for preconditioning MSCs appears to be by culturing MSCs in 3D culture systems, a system that further mimics the complexity of physiological conditions, namely by allowing better cell-to-cell and cell-to-extracellular matrix (ECM) interactions (Fig. 3) [8], [38], [39].”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [8]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 64

  1. [1]Hyrich KL Symmons DPM Watson KD Silman AJ Comparison of the response to infliximab or etanercept monotherapy with the response to cotherapy with methotrexate or another disease-modifying antirheumatic drug in patients with rheumatoid arthritis. Arthritis Rheum. (2006) 54: 1786– 94. 10.1002/art.21830 16736520 · DOI
  2. [2]Listing J Strangfeld A Rau R Kekow J Gromnica-Ihle E Klopsch T. Clinical and functional remission: even though biologics are superior to conventional DMARDs overall success rates remain low - Results from RABBIT, the German biologics register. Arthritis Res Ther. (2006) 8: R66. 10.1186/ar1933 16600016 PMC1526636 · DOI
  3. [3]Müller-Ladner U Pap T Gay RE Neidhart M Gay S. Mechanisms of Disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nat Clin Pract Rheumatol. (2005) 1: 102– 10. 10.1038/ncprheum0047 16932639 · DOI
  4. [4]Fontaine MJ Shih H Schäfer R Pittenger MF. Unraveling the mesenchymal stromal cells' paracrine immunomodulatory effects. Transfus Med Rev. (2016) 30: 37– 43. 10.1016/j.tmrv.2015.11.004 26689863 · DOI · Paper page
  5. [5]Ryan JM Barry FP Murphy JM Mahon BP. Mesenchymal stem cells avoid allogeneic rejection. J Inflamm. (2005) 2: 8. 10.1186/1476-9255-2-8 16045800 PMC1215510 · DOI
  6. [6]Bárcia RN Santos JM Filipe M Teixeira M Martins JP Almeida J. What makes umbilical cord tissue-derived mesenchymal stromal cells superior immunomodulators when compared to bone marrow derived mesenchymal stromal cells? Stem Cells Int. (2015) 2015: 583984. 10.1155/2015/583984 26064137 PMC4443932 · DOI
  7. [7]Moll G Jitschin R von Bahr L Rasmusson-Duprez I Sundberg B Lönnies L. Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses. PLoS ONE (2011) 6: e21703. 10.1371/journal.pone.0021703 21747949 PMC3128611 · DOI
  8. [8]Sun L Akiyama K Zhang H Yamaza T Hou Y Zhao S. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells (2009) 27: 1421– 32. 10.1002/stem.68 19489103 PMC2704254 · DOI
  9. [9]Zappia E Casazza S Pedemonte E Benvenuto F Bonanni I Gerdoni E. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood (2005) 106: 1755– 61. 10.1182/blood-2005-04-1496 15905186 · DOI
  10. [10]Cho KS Park HK Park HY Jung JS Jeon SG Kim YK. IFATS collection: immunomodulatory effects of adipose tissue-derived stem cells in an allergic rhinitis mouse model. Stem Cells (2009) 27: 259– 65. 10.1634/stemcells.2008-0283 18832595 · DOI
  11. [11]English K Wood KJ. Mesenchymal stromal cells in transplantation rejection and tolerance. Cold Spring Harb Perspect Med. (2013) 3: a015560. 10.1101/cshperspect.a015560 23637312 PMC3633184 · DOI
  12. [12]Ansboro S Roelofs AJ De Bari C. Mesenchymal stem cells for the management of rheumatoid arthritis: immune modulation, repair or both? Curr Opin Rheumatol. (2017) 29: 201– 7. 10.1097/BOR.0000000000000370 27941390 · DOI
  13. [13]Kehoe O Cartwright A Askari A El Haj AJ Middleton J. Intra-articular injection of mesenchymal stem cells leads to reduced inflammation and cartilage damage in murine antigen-induced arthritis. J Transl Med. (2014) 12: 157. 10.1186/1479-5876-12-157 24893776 PMC4053306 · DOI
  14. [14]Kay AG Long G Tyler G Stefan A Broadfoot SJ Piccinini AM. Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis. Sci Rep. (2017) 7: 18019. 10.1038/s41598-017-18144-w 29269885 PMC5740178 · DOI
  15. [15]Chen FH Tuan RS. Mesenchymal stem cells in arthritic diseases. Arthritis Res Ther. (2008) 10: 223. 10.1186/ar2514 18947375 PMC2592798 · DOI
  16. [16]Cipriano M Correia JC Camões SP Oliveira NG Cruz P Cruz H. The role of epigenetic modifiers in extended cultures of functional hepatocyte-like cells derived from human neonatal mesenchymal stem cells. Arch Toxicol. (2017) 91: 2469– 89. 10.1007/s00204-016-1901-x 27909741 · DOI
  17. [17]Cipriano M Freyer N Knöspel F Oliveira NG Barcia R Cruz PE. Self-assembled 3D spheroids and hollow-fibre bioreactors improve MSC-derived hepatocyte-like cell maturation in vitro. Arch Toxicol. (2017) 91: 1815– 32. 10.1007/s00204-016-1838-0 27590069 · DOI
  18. [18]Miranda JP Filipe E Fernandes AS Almeida JM Martins JP De La Fuente A. The human umbilical cord tissue-derived MSC population UCX ® promotes early motogenic effects on keratinocytes and fibroblasts and G-CSF-mediated mobilization of BM-MSCs when transplanted in vivo. Cell Transplant. (2015) 24: 865– 77. 10.3727/096368913X676231 24480602 · DOI · Paper page
  19. [20]Santos JM Bárcia RN Simões SI Gaspar MM Calado S Água-Doce A. The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX®) in the treatment of inflammatory arthritis. J Transl Med. (2013) 11: 18. 10.1186/1479-5876-11-18 23324136 PMC3561123 · DOI
  20. [22]Martins JP Santos JM de Almeida JM Filipe MA de Almeida MVT Almeida SCP. Towards an advanced therapy medicinal product based on mesenchymal stromal cells isolated from the umbilical cord tissue: quality and safety data. Stem Cell Res Ther. (2014) 5: 9. 10.1186/scrt398 24438697 PMC4055140 · DOI
  21. [23]Tostões RM Leite SB Serra M Jensen J Björquist P Carrondo MJT. Human liver cell spheroids in extended perfusion bioreactor culture for repeated-dose drug testing. Hepatology (2012) 55: 1227– 36. 10.1002/hep.24760 22031499 · DOI
  22. [24]Simões SI Delgado TC Lopes RM Jesus S Ferreira AA Morais JA. Developments in the rat adjuvant arthritis model and its use in therapeutic evaluation of novel non-invasive treatment by SOD in Transfersomes. J Control Release (2005) 103: 419– 34. 10.1016/j.jconrel.2004.12.008 15763624 · DOI
  23. [25]Schmidt MB Chen EH Lynch SE. A review of the effects of insulin-like growth factor and platelet derived growth factor on in vivo cartilage healing and repair. Osteoarthr Cartil. (2006) 14: 403– 12. 10.1016/j.joca.2005.10.011 16413799 · DOI
  24. [26]Meyer M Muller AK Yang J Moik D Ponzio G Ornitz DM. FGF receptors 1 and 2 are key regulators of keratinocyte migration in vitro and in wounded skin. J Cell Sci. (2012) 125: 5690– 701. 10.1242/jcs.108167 22992463 PMC3575704 · DOI
  25. [27]Bernardini G Spinetti G Ribatti D Camarda G Morbidelli L Ziche M. I-309 binds to and activates endothelial cell functions and acts as an angiogenic molecule in vivo. Blood (2000) 96: 4039– 45. 11110671
  26. [28]Kent D Copley M Benz C Dykstra B Bowie M Eaves C. Regulation of hematopoietic stem cells by the steel factor/KIT signaling pathway. Clin Cancer Res. (2008) 14: 1926– 30. 10.1158/1078-0432.CCR-07-5134 18381929 · DOI
  27. [29]Truong M-D Choi BH Kim YJ Kim MS Min B-H. Granulocyte macrophage – colony stimulating factor (GM-CSF) significantly enhances articular cartilage repair potential by microfracture. Osteoarthr Cartil. (2017) 25: 1345– 52. 10.1016/j.joca.2017.03.002 28284999 · DOI
  28. [30]Yoshida Y Tanaka T. Interleukin 6 and rheumatoid arthritis. Biomed Res Int. (2014) 2014: 698313. 10.1155/2014/698313 24524085 PMC3913495 · DOI
  29. [31]Liu SH Wong CS Chang DM. Increased monocyte chemoattractant protein-1 in knee joints of rats with adjuvant-induced arthritis: in vivo microdialysis. J Rheumatol. (2005) 32: 2205– 11. 16265704
  30. [32]Dinesh P Rasool M. Multifaceted role of IL-21 in rheumatoid arthritis: Current understanding and future perspectives. J Cell Physiol. (2018) 233: 3918– 28. 10.1002/jcp.26158 28833093 · DOI
  31. [33]Khan IM Palmer EA Archer CW. Fibroblast growth factor-2 induced chondrocyte cluster formation in experimentally wounded articular cartilage is blocked by soluble Jagged-1. Osteoarthr Cartil. (2010) 18: 208– 19. 10.1016/j.joca.2009.08.011 19748609 · DOI
  32. [34]Wang Y Lou S. Direct protective effect of interleukin-10 on articular chondrocytes in vitro. Chin Med J. (2001) 114: 723– 5. 11780336
  33. [35]Wroblewski J Edwall C. PDGF BB stimulates proliferation and differentiation in cultured chondrocytes from rat rib growth plate. Cell Biol Int Rep. (1992) 16: 133– 44. 10.1016/S0309-1651(06)80107-4 1551145 · DOI
  34. [36]Duncan MR Berman B. Stimulation of collagen and glycosaminoglycan production in cultured human adult dermal fibroblasts by recombinant human interleukin 6. J Invest Dermatol. (1991) 97: 686– 92. 10.1111/1523-1747.ep12483971 1940439 · DOI
  35. [37]Tsuchida AI Beekhuizen M Rutgers M van Osch GJ Bekkers JE Bot AG. Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model. Arthritis Res Ther. (2012) 14: R262. 10.1186/ar4107 23206933 PMC3674617 · DOI
  36. [38]Alzabin S Williams RO. Effector T cells in rheumatoid arthritis: lessons from animal models. FEBS Lett. (2011) 585: 3649– 59. 10.1016/j.febslet.2011.04.034 21515267 · DOI
  37. [39]Ito T Sawada R Fujiwara Y Tsuchiya T. FGF-2 increases osteogenic and chondrogenic differentiation potentials of human mesenchymal stem cells by inactivation of TGF-β signaling. Cytotechnology (2008) 56: 1– 7. 10.1007/s10616-007-9092-1 19002835 PMC2151969 · DOI
  38. [40]Kay J Calabrese L. The role of interleukin-1 in the pathogenesis of rheumatoid arthritis. Rheumatology (2004) 43: iii2– 9. 10.1093/rheumatology/keh201 15150426 · DOI
  39. [41]Manabe N Oda H Nakamura K Kuga Y Uchida S Kawaguchi H. Involvement of fibroblast growth factor-2 in joint destruction of rheumatoid arthritis patients. Rheumatology (1999) 38: 714– 20. 10.1093/rheumatology/38.8.714 10501417 · DOI
  40. [42]Shao X Chen S Yang D Cao M Yao Y Wu Z. FGF2 cooperates with IL-17 to promote autoimmune inflammation. Sci Rep. (2017) 7: 7024. 10.1038/s41598-017-07597-8 28765647 PMC5539112 · DOI
  41. [43]Wang JY Roehrl MH. Glycosaminoglycans are a potential cause of rheumatoid arthritis. Proc Natl Acad Sci USA. (2002) 99: 14362– 7. 10.1073/pnas.222536599 12391302 PMC137889 · DOI
  42. [44]Sabat R Grütz G Warszawska K Kirsch S Witte E Wolk K. Biology of interleukin-10. Cytokine Growth Factor Rev. (2010) 21: 331– 44. 10.1016/j.cytogfr.2010.09.002 21115385 · DOI · Paper page
  43. [45]Iyer SS Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol. (2012) 32: 23– 63. 10.1615/CritRevImmunol.v32.i1.30 22428854 PMC3410706 · DOI · Paper page
  44. [46]Anderson CF Oukka M Kuchroo VJ Sacks D. CD4 + CD25 – Foxp3 – Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. J Exp Med. (2007) 204: 285– 97. 10.1084/jem.20061886 17283207 PMC2118728 · DOI
  45. [47]Greenhill CJ Jones GW Nowell MA Newton Z Harvey AK Moideen AN. Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction. Arthritis Res Ther. (2014) 16: 419. 10.1186/s13075-014-0419-y 25175678 PMC4292830 · DOI
  46. [48]Carter NA Rosser EC Mauri C. Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis. Arthritis Res Ther. (2012) 14: R32. 10.1186/ar3736 22315945 PMC3392827 · DOI
  47. [49]Venkatesha S Dudics S Acharya B Moudgil K. Cytokine-modulating strategies and newer cytokine targets for arthritis therapy. Int J Mol Sci. (2015) 16: 887– 906. 10.3390/ijms16010887 25561237 PMC4307281 · DOI
  48. [50]Metcalfe SM Muthukumarana PA Thompson HL Haendel MA Lyons GE. Leukaemia inhibitory factor (LIF) is functionally linked to axotrophin and both LIF and axotrophin are linked to regulatory immune tolerance. FEBS Lett. (2005) 579: 609– 14. 10.1016/j.febslet.2004.12.027 15670816 · DOI
  49. [51]Mahic M Kalland ME Aandahl EM Torgersen KM Taskén K. Human naturally occurring and adaptive regulatory T cells secrete high levels of leukaemia inhibitory factor upon activation. Scand J Immunol. (2008) 68: 391– 6. 10.1111/j.1365-3083.2008.02148.x 18782268 · DOI
  50. [52]Muthukumarana PA Lyons GE Miura Y Thompson LH Watson T Green CJ. Evidence for functional inter-relationships between FOXP3, leukaemia inhibitory factor, and axotrophin/MARCH-7 in transplantation tolerance. Int Immunopharmacol. (2006) 6: 1993– 2001. 10.1016/j.intimp.2006.09.015 17161353 · DOI
  51. [53]Knight D. Leukaemia Inhibitory Factor (LIF): a cytokine of emerging importance in chronic airway inflammation. Pulm Pharmacol Ther. (2001) 14: 169– 76. 10.1006/pupt.2001.0282 11448143 · DOI
  52. [54]Bowie MB Kent DG Copley MR Eaves CJ. Steel factor responsiveness regulates the high self-renewal phenotype of fetal hematopoietic stem cells. Blood (2007) 109: 5043– 8. 10.1182/blood-2006-08-037770 17327414 · DOI
  53. [55]Geissler EN Liao M Brook JD Martin FH Zsebo KM Housman DE. Stem cell factor (SCF), a novel hematopoietic growth factor and ligand for c-kit tyrosine kinase receptor, maps on human chromosome 12 between 12q14.3 and 12qter. Somat Cell Mol Genet. (1991) 17: 207– 14. 10.1007/BF01232978 1707188 · DOI
  54. [56]Avci AB Feist E Burmester GR. Targeting GM-CSF in rheumatoid arthritis. Clin Exp Rheumatol. (2016) 34: 39– 44. 27586802
  55. [57]Shi Y Liu CH Roberts AI Das J Xu G Ren G. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don't know. Cell Res. (2006) 16: 126– 33. 10.1038/sj.cr.7310017 16474424 · DOI
  56. [58]Schall TJ Bacon K Camp RDR Kaspari JW Goeddel DV. Human macrophage inflammatory protein alpha (MIP-1 alpha) and MIP-1 beta chemokines attract distinct populations of lymphocytes. J Exp Med. (1993) 177: 1821– 6. 10.1084/jem.177.6.1821 7684437 PMC2191042 · DOI
  57. [59]Robinson E Keystone EC Schall TJ Gillett N Fish EN Chemokine expression in rheumatoid arthritis (RA): evidence of RANTES and macrophage inflammatory protein (MIP)-1β production by synovial T cells. Clin Exp Immunol. (1995) 101: 398– 407. 10.1111/j.1365-2249.1995.tb03126.x 7545093 PMC1553247 · DOI
  58. [60]Pavkova Goldbergova M Lipkova J Pavek N Gatterova J Vasku A Soucek M. RANTES, MCP-1 chemokines and factors describing rheumatoid arthritis. Mol Immunol. (2012) 52: 273– 8. 10.1016/j.molimm.2012.06.006 22750227 · DOI
  59. [61]Moschovakis GL Bubke A Friedrichsen M Ristenpart J Back JW Falk CS. The chemokine receptor CCR7 is a promising target for rheumatoid arthritis therapy. Cell Mol Immunol. (2018) 10.1038/s41423-018-0056-5 29973648 PMC6804778 · DOI
  60. [62]Garcia-Zepeda EA Rothenberg ME Ownbey RT Celestin J Leder P Luster AD. Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia. Nat Med. (1996) 2: 449– 56. 10.1038/nm0496-449 8597956 · DOI
  61. [63]Williams TJ. Eotaxin-1 (CCL11). Front Immunol. (2015) 6: 84. 10.3389/fimmu.2015.00084 25759694 PMC4338813 · DOI
  62. [64]Harigai M Hara M Yoshimura T Leonard EJ Inoue K Kashiwazaki S. Monocyte chemoattractant protein-1 (MCP-1) in inflammatory joint diseases and its involvement in the cytokine network of rheumatoid synovium. Clin Immunol Immunopathol. (1993) 69: 83– 91. 10.1006/clin.1993.1153 8403545 · DOI
  63. [65]Ohshima S Saeki Y Mima T Sasai M Nishioka K Nomura S. Interleukin 6 plays a key role in the development of antigen-induced arthritis. Proc Natl Acad Sci USA. (1998) 95: 8222– 6. 10.1073/pnas.95.14.8222 9653168 PMC20957 · DOI · Paper page
  64. [66]Shahrara S Proudfoot AEI Park CC Volin MV Haines GK Woods JM. Inhibition of monocyte chemoattractant protein-1 ameliorates rat adjuvant-induced arthritis. J Immunol. (2008) 180: 3447– 56. 10.4049/jimmunol.180.5.3447 18292571 · DOI

Cited by

Sorted by citations

Authors
Miranda, J. P., Camões, S. P., Gaspar, M. M., Rodrigues, J. S., Carvalheiro, M., Bárcia, R. N., Cruz, P., Cruz, H., Simões, S., & Santos, J. M.
Affiliations
  • University of Lisbon (PT)
  • ECBio (Portugal) (PT)
  • Universidade do Porto (PT)
Corresponding author
Miranda, Joana P.
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2019-02-05
Volume
10
Pages
18-18
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2019.00018
PMC
PMC6370626
OpenAlex
W2914373166
Cited by
109
References
1
Citations by year
2026: 6 · 2025: 12 · 2024: 14 · 2023: 16 · 2022: 26 · 2021: 20 · 2020: 9 · 2019: 6
FWCI
8.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
Funders
Fundação para a Ciência e a Tecnologia (EXPL/DTP-FTO/0308/2013, TUBITAK/003/2014, UID/DTP/04138/2013, PTDC/MED-TOX/29183/2017, PTDC/SAU-SER/30197/2017)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
Keywords
rheumatoid arthritis, human umbilical cord mesenchymal stem cells, secretome, 3D cell culture, conditioned medium, cell-free therapy, adjuvant-induced arthritis, anti-inflammatory cytokines, glycosaminoglycan synthesis, paracrine signaling, immunomodulation
MeSH terms
Animals, Arthritis, Rheumatoid, Biopsy, Cells, Cultured, Disease Models, Animal, Glycosaminoglycans, Umbilical Cord, Biomarkers, Chondrocytes, Proteome, Proteomics, Mesenchymal Stem Cell Transplantation, Mice, Rats, Mesenchymal Stem Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review