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

作　　者：Bruno C Menarim James N MacLeod Linda A Dahlgren 

机构地区：[1]Gluck Equine Research Center,Department of Veterinary Science,College of Agriculture,Food and Environment,University of Kentucky,Lexington,KY 40546,United States [2]Department of Large Animal Clinical Sciences,Virginia-Maryland College of Veterinary Medicine,Virginia Tech,Blacksburg,VA 24060,United States

出　　处：《World Journal of Stem Cells》2021年第7期825-840,共16页世界干细胞杂志（英文版）（电子版）

摘　　要：Osteoarthritis(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 macrophagemediated resolution of joint inflammation and those required for eff

关 键 词：OSTEOARTHRITIS ARTHROPATHY SYNOVITIS Hematopoietic progenitor HOMEOSTASIS Cell therapy 

分 类 号：R684.3[医药卫生—骨科学]