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Bone marrow mononuclear cells for joint therapy: The role of macrophages in inflammation resolution and tissue repair

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dc.contributor.authorMenarim, Bruno C.en
dc.contributor.authorMacLeod, James N.en
dc.contributor.authorDahlgren, Linda A.en
dc.contributor.departmentLarge Animal Clinical Sciencesen
dc.date.accessioned2021-08-10T15:38:34Zen
dc.date.available2021-08-10T15:38:34Zen
dc.date.issued2021-07-26en
dc.date.updated2021-08-10T15:37:14Zen
dc.description.abstractOsteoarthritis (OA) is the most prevalent joint disease causing major disability and medical expenditures. Synovitis is a central feature of OA and is primarily driven by macrophages. Synovial macrophages not only drive inflammation but also its resolution, through a coordinated, simultaneous expression of pro- and anti-inflammatory mechanisms that are essential to counteract damage and recover homeostasis. Current OA therapies are largely based on anti-inflammatory principles and therefore block pro-inflammatory mechanisms such as prostaglandin E2 and Nuclear factor-kappa B signaling pathways. However, such mechanisms are also innately required for mounting a pro-resolving response, and their blockage often results in chronic low-grade inflammation. Following minor injury, macrophages shield the damaged area and drive tissue repair. If the damage is more extensive, macrophages incite inflammation recruiting more macrophages from the bone marrow to maximize tissue repair and ultimately resolve inflammation. However, sustained damage and inflammation often overwhelms pro-resolving mechanisms of synovial macrophages leading to the chronic inflammation and related tissue degeneration observed in OA. Recently, experimental and clinical studies have shown that joint injection with autologous bone marrow mononuclear cells replenishes inflamed joints with macrophage and hematopoietic progenitors, enhancing mechanisms of inflammation resolution, providing remarkable and long-lasting effects. Besides creating an ideal environment for resolution with high concentrations of interleukin-10 and anabolic growth factors, macrophage progenitors also have a direct role in tissue repair. Macrophages constitute a large part of the early granulation tissue, and further transdifferentiate from myeloid into a mesenchymal phenotype. These cells, characterized as fibrocytes, are essential for repairing osteochondral defects. Ongoing "omics" studies focused on identifying key drivers of macrophage-mediated resolution of joint inflammation and those required for efficient osteochondral repair, have the potential to uncover ways for developing engineered macrophages or off-the-shelf pro-resolving therapies that can benefit patients suffering from many types of arthropaties, not only OA.en
dc.description.versionPublished versionen
dc.format.extentPages 825-840en
dc.format.extent16 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.4252/wjsc.v13.i7.825en
dc.identifier.issn1948-0210en
dc.identifier.issue7en
dc.identifier.orcidDahlgren, Linda [0000-0002-3825-7763]en
dc.identifier.pmid34367479 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/104622en
dc.identifier.volume13en
dc.language.isoenen
dc.publisherBaishidengen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000679408700007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.subjectLife Sciences & Biomedicineen
dc.subjectCell & Tissue Engineeringen
dc.subjectCell Biologyen
dc.subjectOsteoarthritisen
dc.subjectArthropathyen
dc.subjectSynovitisen
dc.subjectHematopoietic progenitoren
dc.subjectHomeostasisen
dc.subjectCell therapyen
dc.subjectMESENCHYMAL STEM-CELLSen
dc.subjectAUTOLOGOUS CONDITIONED SERUMen
dc.subjectKNEE OSTEOARTHRITISen
dc.subjectSYNOVIAL BIOPSIESen
dc.subjectDIFFERENTIATIONen
dc.subjectINTERLEUKIN-10en
dc.subjectCARTILAGEen
dc.subjectIL-10en
dc.subjectCHONDROCYTESen
dc.subjectCYTOKINESen
dc.titleBone marrow mononuclear cells for joint therapy: The role of macrophages in inflammation resolution and tissue repairen
dc.title.serialWorld Journal of Stem Cellsen
dc.typeArticle - Refereeden
dc.typeBook reviewen
dc.type.dcmitypeTexten
dc.type.otherJournalen
dcterms.dateAccepted2021-06-22en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Large Animal Clinical Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

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