Immunology and cartilage regeneration

Abstract

The intrinsic regenerative capacity of avascular cartilage is limited. Cartilage injuries result in chronic, non-healing lesions requiring surgical management. Frequently, these surgical techniques make use of allogeneic cells and tissues. This review discusses the immune status of these materials. Cartilage allografts, often used in orthopedic and plastic surgeries, have rarely provoked a significant immune response. In whole cartilage transplants, the dense matrix produced by chondrocytes inhibits lymphocyte migration, preventing immune detection rendering them "antigen sequestered." It is unclear whether isolated chondrocytes are immune-privileged; chondrocytes express immune inhibitory B7 molecules, indicating that they have some ability to modulate immune reactions. Allogeneic cartilage grafts often involve a bony portion often retaining immunogenic cells and proteins-to facilitate good surgical attachment and concern that this may enhance inflammation and immune rejection. However, studies of failed cartilage grafts have not found immune responses to be a contributing factor. Meniscus allografts, which also retain a bony portion, raise similar concerns as cartilage allografts. Despite this, the plugs improved patient outcomes, indicating that the immunological effects were not clinically significant. Finally, allogeneic mesenchymal stromal cells (MSCs) also are being investigated as a treatment for cartilage damage. MSCs have been demonstrated to have unique immunomodulatory properties including their ability to reduce immune cell infiltration and to modulate inflammation. In summary, the immunogenic properties of cartilage vary with the type of allograft used: Cartilage allografts demonstrate active immune-suppressive mechanisms as evidenced by lack of allograft rejection, while MSC allografts appear to be safe for transplantation.

Age-dependent differences in response to partial-thickness cartilage defects in a rat model as a measure to evaluate the efficacy of interventions for cartilage repair

“…PBS group (7.83 ± 0.98) vs. PRP group (6.50 ± 0.84) (p = 0.162), MSC + PBS group (4.67 ± 0.82) (p = 0.020) and MSC + PRP group (4.50 ± 0.84) (p = 0.015); PRP group vs. MSC + PBS group (p = 0.037) and MSC + PRP group (p = 0.015); and MSC + PBS group vs. MSC + PRP group (p = 0.999) to become an effective alternative treatment material because MSCs pose few problems in the donor side with harvesting, easily proliferate in culture and easily differentiate into chondrocytes (Agung et al 2006;Shirasawa et al 2006). They speculated migrated MSCs worked as a cell source for repair tissue but recent studies reported an immunomodulatory function of MSCs as another possible mechanism for tissue repair (Nam et al 2018;Smith et al 2015). Various tissues have been evaluated as sources of MSCs and synoviumderived stem cells (SDSCs) are considered to have the greatest potential for expansion and chondrogenesis, compared with other MSC sources (De Bari et al 2001;Sakaguchi et al 2005).…”

Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair

“…Chondrocytes reside in small compartmented cavities called lacunae that are surrounded by large areas of dense cartilage ECM making it difficult for these cells to move freely or migrate in response to biological cues of damaged tissue. Moreover, the lack of blood vasculature prevents the infiltration of articular cartilage by circulating immune cells [212]. Multiple approaches have been documented to help restore cartilage without surgical proceedings, but the fact remains that there are virtually no clinical treatment options in existence that completely restore damaged articular cartilage to its native state [213][214][215][216][217].…”

Xenotransplantation of pig chondrocytes: therapeutic potential and barriers for cartilage repair

“…Despite the clinical benefit attained with meniscus allotransplantation and osteochondral allograft transplantation Gracitelli et al, 2015), some concerns have been raised about the potential detrimental effects of the elicited immune response. Evidence is accumulating of the immune-privileged properties of cartilage, but isolated chondrocytes and especially the bony portion of the osteochondral grafts are more immunogenic (Smith et al, 2015). Early work pointed out that allogeneic chondrocytes may elicit an immune response when injected heterotopically in rats (Romaniuk et al, 1995).…”