Skip to main content

Are We Right to Consider Mesenchymal Stem Cells to Be a New Perspective for Patients with Juvenile Idiopathic Arthritis?

Archivum Immunologiae et Therapiae Experimentalis volume 66, pages 267–271 (2018)Cite this article

Abstract

Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in childhood. Up to 50% of patients are resistant to standard therapy, which includes non-steroid anti-inflammatory drugs, corticosteroids, disease-modifying anti-rheumatic drugs and biologic therapies. Intra-articular injection of mesenchymal stem cells (MSCs) is proposed as a new approach to JIA treatment. MSCs can modulate inflammation via mechanisms of both adaptive and innate immune response. They are able to inhibit T and B cell proliferation, promote regulatory T cells, suppress the maturation of dendritic cells, stimulate macrophage differentiation into M2 phenotype and reduce effectiveness of natural killer cells. They also secrete plethora of soluble factors which influence joint inflammation. Recent clinical studies reviewed in the article provide promising results which may suggest including intra-articular injection of MSCs in therapy of patients with oligoarticular JIA.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1

References

  • Abdelrazik H, Spaggiari GM, Chiossone L et al (2011) Mesenchymal stem cells expanded in human platelet lysate display a decreased inhibitory capacity on T- and NK-cell proliferation and function. Eur J Immunol 41:3281–3290

    Article  PubMed  CAS  Google Scholar 

  • Ansboro S, Roelofs AJ, De Bari C (2017) Mesenchymal stem cells for the management of rheumatoid arthritis: immune modulation, repair or both? Curr Opin Rheumatol 29:201–207

    Article  PubMed  CAS  Google Scholar 

  • Bartholomew A, Sturgeon C, Siatskas M et al (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42–48

    Article  PubMed  Google Scholar 

  • Bocelli-Tyndall C, Bracci L, Spagnoli G et al (2007) Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and auto-immune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro. Rheumatology 46:403–408

    Article  PubMed  CAS  Google Scholar 

  • Burt RK, Slavin S, Burns WH, Marmont AM (2002) Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure? Blood 99:768–784

    Article  PubMed  CAS  Google Scholar 

  • Calkoen FG, Brinkman DM, Vervat C et al (2013) Mesenchymal stromal cells isolated from children with systemic juvenile idiopathic arthritis suppress innate and adaptive immune responses. CytoTherapy 15:280–291

    Article  PubMed  CAS  Google Scholar 

  • Cipriani P, Carubbi F, Liakouli V et al (2013) Stem cells in autoimmune diseases: Implications for pathogenesis and future trends in therapy. Autoimmun Rev 12:709–716

    Article  PubMed  CAS  Google Scholar 

  • Colter DC, Class R, DiGirolamo CM et al (2000) Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow. Proc Natl Acad Sci USA 97:3213–3218

    Article  PubMed  CAS  Google Scholar 

  • Contreras RA, Figueroa FE, Djouad F et al (2016) Mesenchymal stem cells regulate the innate and adaptive immune responses dampening arthritis progression. Stem Cells Int 2016:3162743

  • Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 28:875–884

    Article  PubMed  CAS  Google Scholar 

  • Di Nicola M, Carlo-Stella C, Magni M et al (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838–3843

    Article  PubMed  Google Scholar 

  • Djouad F, Bony C, Haupl T et al (2005) Transcriptional profiles discriminate bone marrow-derived and synovium-derived mesenchymal stem cells. Arthritis Res Ther 7:R1304–R1315

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • English K (2013) Mechanisms of mesenchymal stromal cell immunomodulation. Immunol Cell Biol 91:19–26

    Article  PubMed  CAS  Google Scholar 

  • Friedenstein AJ, Chailakhyan RK, Latsinik NV et al (1974) Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 17:331–340

    Article  PubMed  CAS  Google Scholar 

  • Giancane G, Consolaro A, Lanni S et al (2016) Juvenile idiopathic arthritis: diagnosis and treatment. Rheumatol Ther 3:187–207

    Article  PubMed  PubMed Central  Google Scholar 

  • Hahn YS, Kim JG (2010) Pathogenesis and clinical manifestations of juvenile rheumatoid arthritis. Korean J Pediatr 53:921–930

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hinks A, Cobb J, Marion MC et al (2013) Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis. Nat Genet 45:664–669

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hou J, Ouyang Y, Deng H et al (2016) Whole-genome expression analysis and signal pathway screening of synovium-derived mesenchymal stromal cells in rheumatoid arthritis. Stem Cells Int 2016:1375031

  • Huang JL (2012) New advances in juvenile idiopathic arthritis. Chang Gung Med J 35:1–14

    PubMed  Google Scholar 

  • Jo CH, Lee YG, Shin WH et al (2014) Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells 32:1254–1266

    Article  PubMed  CAS  Google Scholar 

  • Jorgensen C, Djouad F, Apparailly F et al (2003) Engineering mesenchymal stem cells for immunotherapy. Gene Ther 10:928–931

    Article  PubMed  CAS  Google Scholar 

  • Kastrinaki MC, Sidiropoulos P, Roche S et al (2008) Functional, molecular and proteomic characterisation of bone marrow mesenchymal stem cells in rheumatoid arthritis. Ann Rheum Dis 67:741–749

    Article  PubMed  CAS  Google Scholar 

  • MacFarlane RJ, Graham SM, Davies PS et al (2013) Anti-inflammatory role and immunomodulation of mesenchymal stem cells in systemic joint diseases: potential for treatment. Expert Opin Ther Targets 17:243–254

    Article  PubMed  CAS  Google Scholar 

  • McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429–442

    Article  PubMed  CAS  Google Scholar 

  • Melief SM, Zwaginga JJ, Fibbe WE et al (2013) Adipose tissue-derived multipotent stromal cells have a higher immunomodulatory capacity than their bone marrow-derived counterparts. Stem Cells Transl Med 2:455–463

    Article  PubMed  PubMed Central  Google Scholar 

  • Nemeth K, Leelahavanichkul A, Yuen PS et al (2009) Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 15:42–49

    Article  PubMed  CAS  Google Scholar 

  • Nie Y, Lau C, Lie A et al (2010) Defective phenotype of mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus 19:850–859

    Article  PubMed  CAS  Google Scholar 

  • Noel D, Djouad F, Jorgense C (2002) Regenerative medicine through mesenchymal stem cells for bone and cartilage repair. Curr Opin Investig Drugs 3:1000–1004

    PubMed  Google Scholar 

  • Norambuena GA, Khoury M, Jorgensen C (2012) Mesenchymal stem cells in osteoarticular pediatric diseases: an update. Pediatr Res 71:452–458

    Article  PubMed  CAS  Google Scholar 

  • Park MJ, Lee SH, Moon SJ et al (2016) Overexpression of soluble RAGE in mesenchymal stem cells enhances their immunoregulatory potential for cellular therapy in autoimmune arthritis. Sci Rep 6:35933

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Petty RE, Southwood TR, Manners P et al (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31:390–392

    PubMed  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  • Ravelli A, Martini A (2007) Juvenile idiopathic arthritis. The Lancet 369:767–778

    Article  CAS  Google Scholar 

  • Shalev-Malul G, Soler DC, Ting AE et al (2016) Development of a functional biomarker for use in cell-based therapy studies in seropositive rheumatoid arthritis. Stem Cells Transl Med 5:628–6321

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shin TH, Kim HS, Kang TW et al (2016) Human umbilical cord blood-stem cells direct macrophage polarization and block inflammasome activation to alleviate rheumatoid arthritis. Cell Death Dis 7:e2524

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Spaggiari GM, Capobianco A, Abdelrazik H et al (2008) Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 111:1327–1333

    Article  PubMed  CAS  Google Scholar 

  • Swart J, Martens A, Wulffraat N (2008) Mesenchymal stem cells: a future for the treatment of arthritis? Joint Bone Spine 75:379–382

    Article  PubMed  Google Scholar 

  • Swart J, Wulffraat N, Prakken BJ et al (2015) Mesenchymal stromal cell treatment in juvenile idiopathic arthritis: a pilot study [abstract]. Arthritis Rheumatol 67:3813–3814

    Google Scholar 

  • Swidrowska-Jaros J, Orczyk K, Smolewska E (2016) Macrophages - silent enemies in juvenile idiopathic arthritis. Postepy Hig Med Dosw (Online) 70:743–750

    Article  Google Scholar 

  • Uccelli A, de Rosbo NK (2015) The immunomodulatory function of mesenchymal stem cells: mode of action and pathways. Ann N Y Acad Sci 1351:114–126

    Article  PubMed  Google Scholar 

  • Verwoerd A, Ter Haar NM, de Roock S et al (2016) The human microbiome and juvenile idiopathic arthritis. Pediatr Rheumatol Online J 14:55

    Article  PubMed  PubMed Central  Google Scholar 

  • Wakitani S, Okabe T, Horibe S et al (2011) Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J Tissue Eng Regen Med 5:146–150

    Article  PubMed  Google Scholar 

  • Wang L, Zhang Y, Li H et al (2016) Clinical observation of employment of umbilical cord derived mesenchymal stem cell for juvenile idiopathic arthritis therapy. Stem Cells Int 2016:9165267

  • Wu CC, Liu FL, Sytwu HK et al (2016) CD146 + mesenchymal stem cells display greater therapeutic potential than CD146- cells for treating collagen-induced arthritis in mice. Stem Cell Res Ther 7:23

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Y, Khan D, Delling J et al (2012) Mechanisms underlying the osteo- and adipo-differentiation of human mesenchymal stem cells. Sci World J 2012:793823

Download references

Acknowledgements

This work was partially supported by the grant No. 503/8-000-04/503-81-002 from Medical University of Lodz, Poland.

Author information

Affiliations

  1. Department of Pediatric Rheumatology, Medical University of Lodz, Sporna 36/50, 91-738, Lodz, Poland

    Krzysztof Orczyk & Elzbieta Smolewska

Authors
  1. Krzysztof Orczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elzbieta Smolewska
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elzbieta Smolewska.

Ethics declarations

Conflict of interest

Authors declare no conflict of interests.

About this article

Verify currency and authenticity via CrossMark

Cite this article

Orczyk, K., Smolewska, E. Are We Right to Consider Mesenchymal Stem Cells to Be a New Perspective for Patients with Juvenile Idiopathic Arthritis?. Arch. Immunol. Ther. Exp. 66, 267–271 (2018). https://doi.org/10.1007/s00005-017-0493-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-017-0493-3

Keywords

  • Mesenchymal stem cells
  • Juvenile idiopathic arthritis
  • Pathogenesis