Generic placeholder image

Current Rheumatology Reviews

Editor-in-Chief

ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Review Article

Mesenchymal Cells are a Promising -But Still Unsatisfying- Anti- Inflammatory Therapeutic Strategy for Osteoarthritis: A Narrative Review

Author(s): Sergio Rosini, Gianantonio Saviola*, Laura Comini and Luigi Molfetta

Volume 19, Issue 3, 2023

Published on: 28 December, 2022

Page: [287 - 293] Pages: 7

DOI: 10.2174/1573397118666220928141624

Price: $65

conference banner
Abstract

Osteoarthritis (OA) is a chronic disease with both degenerative and inflammatory characteristics, affecting the osteochondral unit with the involvement of cartilage, subchondral bone and periarticular tissues. OA can produce chronic pain with neuropathic and inflammatory characteristics, leading to an increased disability. OA is secondary to many predisposing factors where the inflammatory process plays a key role. To manage OA, it would seem logical to block the factors influencing the inflammatory process at different levels, T lymphocytes, neutrophils, and the balance between phenotype-1 macrophages (M1, pro-inflammatory) and phenotype-2 macrophages (M2 anti-inflammatory), the managing cells. The efforts to repair and rebuild the lost cartilage and the attempts to implant autologous or heterologous material, with or without growth factors and the administration of drugs or the use of medical devices, have failed their objective. TNF-alpha and IL-1 inhibitors can only have a transient effect on pain; intra-articular oxidized Low-Density Lipoproteins are able to stimulate the activation of M2, while growth factors need to be better investigated. Also, intra-articular injections of mesenchymal stem cells (MSC) can inhibit the proliferation of T-lymphocytes, leading to cartilage repair and to osteophytes inhibition thanks to the release of exosomes, nanosized particles which are the active components. Gut microbiota has a potential role in the development of OA and could be able to influence the response to therapeutic agents.

Keywords: osteoarthritis, inflammation, macrophages, phenotype, exosomes, MSC, synovium

[1]
Molfetta L, Casabella A, Rosini S, Saviola G, Palermo A. Role of the osteochondral unit in the pathogenesis of osteoarthritis: Focus on the potential use of clodronate. Curr Rheumatol Rev 2022; 18(1): 2-11.
[http://dx.doi.org/10.2174/1573397117666211006094117] [PMID: 34615451]
[2]
Steinmetz PR, Balko C, David JR. Lymphocyte mediators and cellular hypersensitivity. N Engl J Med 1973; 288(3): 143-9.
[http://dx.doi.org/10.1056/NEJM197301182880311] [PMID: 4567414]
[3]
Nathan CF, Murray HW, Wiebe ME, Rubin BY. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 1983; 158(3): 670-89.
[http://dx.doi.org/10.1084/jem.158.3.670] [PMID: 6411853]
[4]
Abramson SL, Gallin JI. IL-4 inhibits superoxide production by human mononuclear phagocytes. J Immunol 1990; 144(2): 625-30.
[PMID: 2153171]
[5]
Stein M, Keshav S, Harris N, Gordon S. Interleukin 4 potently enhances murine macrophage mannose receptor activity: A marker of alternative immunologic macrophage activation. J Exp Med 1992; 176(1): 287-92.
[http://dx.doi.org/10.1084/jem.176.1.287] [PMID: 1613462]
[6]
Manferdini C, Paolella F, Gabusi E, et al. From osteoarthritic synovium to synovial-derived cells characterization: Synovial macrophages are key effector cells. Arthritis Res Ther 2016; 18(1): 83.
[http://dx.doi.org/10.1186/s13075-016-0983-4] [PMID: 27044395]
[7]
Culemann S, Grüneboom A, Nicolás-Ávila JÁ, et al. Locally renewing resident synovial macrophages provide a protective barrier for the joint. Nature 2019; 572(7771): 670-5.
[http://dx.doi.org/10.1038/s41586-019-1471-1] [PMID: 31391580]
[8]
Zhou D, Huang C, Lin Z, et al. Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. Cell Signal 2014; 26(2): 192-7.
[http://dx.doi.org/10.1016/j.cellsig.2013.11.004] [PMID: 24219909]
[9]
Fernandes TL, Gomoll AH, Lattermann C, Hernandez AJ, Bueno DF, Amano MT. Macrophage: A potential target on cartilage regeneration. Front Immunol 2020; 11: 111.
[http://dx.doi.org/10.3389/fimmu.2020.00111] [PMID: 32117263]
[10]
O’Brien K, Tailor P, Leonard C, et al. Enumeration and localization of mesenchymal progenitor cells and macrophages in synovium from normal individuals and patients with pre-osteoarthritis or clinically diagnosed osteoarthritis. Int J Mol Sci 2017; 18(4): 774.
[http://dx.doi.org/10.3390/ijms18040774] [PMID: 28379175]
[11]
Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: Enabling diversity with identity. Nat Rev Immunol 2011; 11(11): 750-61.
[http://dx.doi.org/10.1038/nri3088] [PMID: 22025054]
[12]
El Chartouni C, Schwarzfischer L, Rehli M. Interleukin-4 induced interferon regulatory factor (IRF) 4 participates in the regulation of alternative macrophage priming. Immunobiology 2010; 215(9-10): 821-5.
[http://dx.doi.org/10.1016/j.imbio.2010.05.031] [PMID: 20580461]
[13]
Malyshev I, Malyshev Y. Current concept and update of the macrophage plasticity concept: Intracellular mechanisms of reprogramming and m3 macrophage “switch” phenotype. BioMed Res Int 2015; 2015: 1-22.
[http://dx.doi.org/10.1155/2015/341308] [PMID: 26366410]
[14]
Tardito S, Martinelli G, Soldano S, et al. Macrophage M1/M2 polarization and rheumatoid arthritis: A systematic review. Autoimmun Rev 2019; 18(11): 102397.
[http://dx.doi.org/10.1016/j.autrev.2019.102397] [PMID: 31520798]
[15]
Deng Z, Zhang Q, Zhao Z, et al. Crosstalk between immune cells and bone cells or chondrocytes. Int Immunopharmacol 2021; 101(Pt A): 108179.
[http://dx.doi.org/10.1016/j.intimp.2021.108179]
[16]
Chaney S, Vergara R, Qiryaqoz Z, Suggs K, Akkouch A. The involvement of neutrophils in the pathophysiology and treatment of osteoarthritis. Biomedicines 2022; 10(7): 1604.
[http://dx.doi.org/10.3390/biomedicines10071604] [PMID: 35884909]
[17]
Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American college of rheumatology/arthritis foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Care Res 2020; 72(2): 149-62.
[http://dx.doi.org/10.1002/acr.24131] [PMID: 31908149]
[18]
Conaghan PG, Cook AD, Hamilton JA, Tak PP. Therapeutic options for targeting inflammatory osteoarthritis pain. Nat Rev Rheumatol 2019; 15(6): 355-63.
[http://dx.doi.org/10.1038/s41584-019-0221-y] [PMID: 31068673]
[19]
Rios FJ, Koga MM, Pecenin M, Ferracini M, Gidlund M, Jancar S. Oxidized LDL induces alternative macrophage phenotype through activation of CD36 and PAFR. Mediators Inflamm 2013; 2013: 1-8.
[http://dx.doi.org/10.1155/2013/198193] [PMID: 24062612]
[20]
Dai M, Sui B, Xue Y, Liu X, Sun J. Cartilage repair in degenerative osteoarthritis mediated by squid type II collagen via immunomodulating activation of M2 macrophages, inhibiting apoptosis and hypertrophy of chondrocytes. Biomaterials 2018; 180: 91-103.
[http://dx.doi.org/10.1016/j.biomaterials.2018.07.011] [PMID: 30031224]
[21]
Dai M, Liu X, Wang N, Sun J. Squid type II collagen as a novel biomaterial: Isolation, characterization, immunogenicity and relieving effect on degenerative osteoarthritis via inhibiting STAT1 signaling in pro-inflammatory macrophages. Mater Sci Eng C 2018; 89: 283-94.
[http://dx.doi.org/10.1016/j.msec.2018.04.021] [PMID: 29752100]
[22]
Harrell CR, Markovic BS, Fellabaum C, Arsenijevic A, Volarevic V. Mesenchymal stem cell-based therapy of osteoarthritis: Current knowledge and future perspectives. Biomed Pharmacother 2019; 109: 2318-26.
[http://dx.doi.org/10.1016/j.biopha.2018.11.099] [PMID: 30551490]
[23]
Djouad F, Bouffi C, Ghannam S, Noël D, Jorgensen C. Mesenchymal stem cells: Innovative therapeutic tools for rheumatic diseases. Nat Rev Rheumatol 2009; 5(7): 392-9.
[http://dx.doi.org/10.1038/nrrheum.2009.104] [PMID: 19568253]
[24]
Kim JE, Lee SM, Kim SH, et al. Effect of self-assembled peptide-mesenchymal stem cell complex on the progression of os-teoarthritis in a rat model. Int J Nanomedicine 2014; 9 (Suppl. 1): 141-57.
[http://dx.doi.org/10.2147/IJN.S54114]
[25]
Mokbel AN, El Tookhy OS, Shamaa AA, Rashed LA, Sabry D, El Sayed AM. Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskelet Disord 2011; 12(1): 259.
[http://dx.doi.org/10.1186/1471-2474-12-259] [PMID: 22085445]
[26]
Barry FP. Biology and clinical applications of mesenchymal stem cells. Birth Defects Res C Embryo Today 2003; 69(3): 250-6.
[http://dx.doi.org/10.1002/bdrc.10021] [PMID: 14671778]
[27]
Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage 2002; 10(3): 199-206.
[http://dx.doi.org/10.1053/joca.2001.0504] [PMID: 11869080]
[28]
Kim JD, Lee GW, Jung GH, et al. Clinical outcome of autologous bone marrow aspirates concentrate (BMAC) injection in degenerative arthritis of the knee. Eur J Orthop Surg Traumatol 2014; 24(8): 1505-11.
[http://dx.doi.org/10.1007/s00590-013-1393-9] [PMID: 24398701]
[29]
von Bahr L, Batsis I, Moll G, et al. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. Stem Cells 2012; 30(7): 1575-8.
[http://dx.doi.org/10.1002/stem.1118] [PMID: 22553154]
[30]
Soler R, Orozco L, Munar A, et al. Final results of a phase I–II trial using ex vivo expanded autologous Mesenchymal Stromal Cells for the treatment of osteoarthritis of the knee confirming safety and suggesting cartilage regeneration. Knee 2016; 23(4): 647-54.
[http://dx.doi.org/10.1016/j.knee.2015.08.013] [PMID: 26783191]
[31]
Matas J, Orrego M, Amenabar D, et al. Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for knee osteoarthritis: Repeated msc dosing is superior to a single MSC dose and to hyaluronic acid in a controlled randomized phase I/II trial. Stem Cells Transl Med 2019; 8(3): 215-24.
[http://dx.doi.org/10.1002/sctm.18-0053] [PMID: 30592390]
[32]
Keshtkar S, Azarpira N, Ghahremani MH. Mesenchymal stem cell-derived extracellular vesicles: Novel frontiers in regenerative medicine. Stem Cell Res Ther 2018; 9(1): 63.
[http://dx.doi.org/10.1186/s13287-018-0791-7] [PMID: 29523213]
[33]
Zhang S, Chu WC, Lai RC, Lim SK, Hui JHP, Toh WS. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis Cartilage 2016; 24(12): 2135-40.
[http://dx.doi.org/10.1016/j.joca.2016.06.022] [PMID: 27390028]
[34]
Ni Z, Zhou S, Li S, et al. Exosomes: Roles and therapeutic potential in osteoarthritis. Bone Res 2020; 8(1): 25.
[http://dx.doi.org/10.1038/s41413-020-0100-9] [PMID: 32596023]
[35]
Kim YG, Choi J, Kim K. Mesenchymal stem cell‐derived exosomes for effective cartilage tissue repair and treatment of osteoarthritis. Biotechnol J 2020; 15(12): 2000082.
[http://dx.doi.org/10.1002/biot.202000082] [PMID: 32559340]
[36]
Mistry H, Connock M, Pink J, et al. Autologous chondrocyte implantation in the knee: Systematic review and economic evaluation. Health Technol Assess 2017; 21(6): 1-294.
[http://dx.doi.org/10.3310/hta21060] [PMID: 28244303]
[37]
Wells T, Davidson C, Mörgelin M, Bird JLE, Bayliss MT, Dudhia J. Age-related changes in the composition, the molecular stoichiometry and the stability of proteoglycan aggregates extracted from human articular cartilage. Biochem J 2003; 370(1): 69-79.
[http://dx.doi.org/10.1042/bj20020968] [PMID: 12431185]
[38]
Felson DT, Anderson JJ, Naimark A, Walker AM, Meenan RF. Obesity and knee osteoarthritis. the framingham study. Ann Intern Med 1988; 109(1): 18-24.
[http://dx.doi.org/10.7326/0003-4819-109-1-18] [PMID: 3377350]
[39]
Beavers KM, Beavers DP, Newman JJ, et al. Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis. Osteoarthritis Cartilage 2015; 23(2): 249-56.
[http://dx.doi.org/10.1016/j.joca.2014.11.005] [PMID: 25450847]
[40]
Vincent HK, Heywood K, Connelly J, Hurley RW. Obesity and weight loss in the treatment and prevention of osteoarthritis. PM R 2012; 4(5): S59-67.
[http://dx.doi.org/10.1016/j.pmrj.2012.01.005] [PMID: 22632704]
[41]
Courties A, Sellam J, Berenbaum F. Metabolic syndrome-associated osteoarthritis. Curr Opin Rheumatol 2017; 29(2): 214-22.
[http://dx.doi.org/10.1097/BOR.0000000000000373] [PMID: 28072592]
[42]
Sellam J, Berenbaum F. Is osteoarthritis a metabolic disease? Joint Bone Spine 2013; 80(6): 568-73.
[http://dx.doi.org/10.1016/j.jbspin.2013.09.007] [PMID: 24176735]
[43]
Dell’Isola A, Allan R, Smith SL, Marreiros SSP, Steultjens M. Identification of clinical phenotypes in knee osteoarthritis: A systematic review of the literature. BMC Musculoskelet Disord 2016; 17(1): 425.
[http://dx.doi.org/10.1186/s12891-016-1286-2] [PMID: 27733199]
[44]
Lucas S, Omata Y, Hofmann J, et al. Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss. Nat Commun 2018; 9(1): 55.
[http://dx.doi.org/10.1038/s41467-017-02490-4] [PMID: 29302038]
[45]
Biver E, Berenbaum F, Valdes AM, et al. Gut microbiota and osteoarthritis management: An expert consensus of the European society for clinical and economic aspects of osteoporosis, osteoarthritis and musculoskeletal diseases (ESCEO). Ageing Res Rev 2019; 55: 100946.
[http://dx.doi.org/10.1016/j.arr.2019.100946] [PMID: 31437484]
[46]
Saidane O, Courties A, Sellam J. Dietary fibers in osteoarthritis: What are the evidences? Joint Bone Spine 2019; 86(4): 411-4.
[http://dx.doi.org/10.1016/j.jbspin.2018.10.010] [PMID: 30471420]
[47]
Henrotin Y, Patrier S, Pralus A, Roche M, Nivoliez A. Protective actions of oral administration of Bifidobacterium longum CBi0703 in spontaneous osteoarthritis in dunkin hartley guinea pig model. Cartilage 2021; 13(2) (Suppl.): 1204S-13S.
[http://dx.doi.org/10.1177/1947603519841674] [PMID: 30982336]
[48]
Wang J, Chen WD, Wang YD. The relationship between gut microbiota and inflammatory diseases: The role of macrophages. Front Microbiol 2020; 11: 1065.
[http://dx.doi.org/10.3389/fmicb.2020.01065] [PMID: 32582063]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy