Abstract
Osteoarthritis (OA) is the most common form of arthritis worldwide. It is a major cause of disability in the adult population with its prevalence expected to increase dramatically over the next 20 years. Although current therapies can alleviate symptoms and improve function in early course of the disease, OA inevitably progresses to end-stage disease requiring total joint arthroplasty. Mesenchymal stromal cells (MSCs) have emerged as a candidate cell type with great potential for intra-articular (IA) repair therapy. However, there is still a considerable lack of knowledge concerning their behaviour, biology and therapeutic effects. To start addressing this, we explored the secretory profile of bone marrow derived MSCs in early and end-stage knee OA synovial fluid (SF).
Subjects were recruited and categorised into early [Kellgren-Lawrence (KL) grade I and II, n=12] and end-stage (KL grade III and IV, n=11) knee OA groups. The SF proteome of early and end-stage OA was tested before and three days after the addition of bone marrow MSCs (16.5×10^3, single donor) using multiplex ELISA (64 cytokines) and mass spectrometry (302 proteins detected). Non parametric Wilcoxon-signed rank test for paired samples was used to compare the levels of proteins before and after addition of MSCs in early and end-stage knee OA SF. Significant differences were determined after multiple comparisons correction (FDR) with a p<0.05.
Gender distribution and BMI were not statistically different between the two cohorts (p>0.05). However, patients in early knee OA cohort were significantly younger (44.7 years, SD=7.1) than patients in the end-stage cohort (58.6 years, SD=4.4; p<0.05). In both early and end-stage knee OA, MSCs increased the levels of VEGF-A (by 320.24 pg/mL), IL-6 (by 826.78 pg/mL) and IL-8 (by 128.85 pg/mL), factors involved in angiogenesis; CXCL1/2/3 (by 103.35 pg/mL), CCL2 (by 1187.27 pg/mL), CCL3 (by 15.82 pg/mL) and CCL7 (by 10.43 pg/mL), growth factors and chemokines. However, CXCL5 (by 48.61 pg/mL) levels increased only in early knee OA, whereas PDGF-AA (by 15.36 pg/mL) and CXCL12 (by 497.19 pg/mL) levels increased only in end-stage knee OA.
This study demonstrates that bone marrow derived MSCs secrete angiogenic and chemotactic factors both in early and end-stage knee OA. More importantly, MSCs show a differential reaction between early and end-stage OA. Functional assays are required to further understand on how the therapeutic effect of MSCs is modulated when exposed to OA SF.
