Abstract
Background: Mesenchymal stem cell (MSC) therapy has emerged as a promising treatment option for knee osteoarthritis. Adipose MSCs are commonly used due to their easy accessibility; however, synovial MSCs have demonstrated a superior capacity for cartilage matrix synthesis. The mechanism underlying this difference in therapeutic efficacy may involve lubricin, a crucial glycoprotein that maintains joint lubrication and protects cartilage. Notably, lubricin levels decrease during the progression of osteoarthritis. The aim of this study was to compare extracellular lubricin secretion by human synovial MSCs versus adipose MSCs. We also analyzed potential correlations between synovial MSC lubricin secretion and synovial inflammation. Methods: Tissues for MSC isolation were obtained from 16 human donors with osteoarthritis who underwent total knee arthroplasty. Synovium was collected from the suprapatellar pouch on the femoral side, whereas adipose tissue was harvested from the subcutaneous layer of the knee skin incision. The synovial and adipose MSCs from each donor were cultured for 48 h (six replicate wells per donor), and lubricin concentrations in culture supernatants were measured using ELISA. For 11 donors, lubricin concentrations were measured directly, whereas the concentrations were normalized to cell number for the other 5 donors. MSC identity was assessed by flow cytometry and trilineage differentiation assays. Correlations between synovial MSC lubricin secretion and clinical parameters, including age, CRP, WBC, numerical rating scale for knee pain, synovial redness, synovial hyperplasia, and Krenn's synovitis score, were assessed. Results: Lubricin secretion was significantly greater from synovial MSCs than from adipose MSCs in 8 of the 11 directly analyzed MSC supernatants (p = 0.014 by Wilcoxon matched-pairs signed-rank test). However, the results from all 5 donors whose lubricin concentrations were normalized to cell number revealed a consistently higher lubricin secretion by synovial MSCs than by adipose MSCs. Every representative preparation of synovial and adipose MSCs fulfilled standard MSC identity criteria. No correlations were found between lubricin secretion and synovial inflammation or any clinical parameters. Conclusions: More lubricin was secreted from human synovial MSCs than from adipose MSCs in the majority of donors examined. These findings support the potential therapeutic advantages of using synovial MSCs for osteoarthritis treatment.