Abstract
IntroductionA major problem in cartilage repair is the lack of chondrogenic cells migrating from healthy tissue into defects. Cartilage is essentially avascular and therefore its healing is not considered to involve mononuclear cells. Peripheral blood derived mononuclear cells (PBMC) offer a readily available autologous cell source for clinical use and therefore this study was designed to evaluate the effects of PBMCs on chondrocytes and cartilage.MethodsHuman primary chondrocytes and cartilage tissue explants were taken from patients undergoing total knee replacement (n = 17). Peripheral blood samples were obtained from healthy volunteers (n = 12) and mononuclear cells were isolated by density-gradient centrifugation. Cell migration and chemokinetic potential were measured using a scratch assay, xCELLigence and CyQuant assay. PCR array and quantitative PCR was used to evaluate mRNA expression of 87 cell motility and/or chondrogenic genes.ResultsThe chondrocyte migration rate was 2.6 times higher at 3 hour time point (p < 0.0001) and total number of migrating chondrocytes was 9.7 times higher (p < 0.0001) after three day indirect PBMC stimulus and 8.2 times higher (p < 0.0001) after three day direct co-culture with PBMCs. A cartilage explant model confirmed that PBMCs also exert a chemokinetic role on ex vivo tissue. PBMC stimulation was found to significantly upregulate the mRNA levels of 2 chondrogenic genes; collagen type II (COL2A1 600–fold, p < 0.0001) and SRY box 9 (SOX9 30–fold, p < 0.0001) and the mRNA levels of 7 genes central in cell motility and migration were differentially regulated by 24h PBMC stimulation.ConclusionThe results support the concept that PBMC treatment enhances chondrocyte migration without suppressing the chondrogenic phenotype possibly via mechanistic pathways involving MMP9 and IGF1. In the future, peripheral blood mononuclear cells could be used as an autologous point-ofcare treatment to attract native chondrocytes from the diseased tissue to aid in cartilage repair.
Highlights
A major problem in cartilage repair is the lack of chondrogenic cells migrating from healthy tissue into defects
The aim of this study was to observe whether Peripheral blood derived mononuclear cells (PBMC) enhance chondrocyte migration without adversely effecting chondrogenicity in order to establish if PBMCs have potential in therapeutic cartilage repair
At 24 h, the scratch width in untreated chondrocyte cultures was reduced by 51 %, whereas with the chondrocytes cultured with PBMCs, it was reduced by 84 % (p = 0.002) (Fig. 2a)
Summary
A major problem in cartilage repair is the lack of chondrogenic cells migrating from healthy tissue into defects. Cartilage is essentially avascular and its healing is not considered to involve mononuclear cells. During our previous studies using explants derived from human osteoarthritic articular cartilage cultured in serum-free conditions we have observed the formation of cell monolayers around the explants after 7–10 days in culture [7]. This evidence suggests that human chondrocytes are capable of substantial migration and this action is likely to be initiated either by pre-existing OA damage or by cutting the tissue. The migratory cells are proliferative and exhibit a phenotype different from chondrocytes [8]
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