Synovial stem cells secrete more lubricin than fat-derived stem cells in knee osteoarthritis donors

Knee osteoarthritis is the most common joint disorder. It involves progressive cartilage breakdown, synovial inflammation, and changes in the knee's fat pad. Standard treatments such as anti-inflammatory drugs, hyaluronic acid injections, and exercise often give limited relief, and many patients eventually need joint replacement. Injecting mesenchymal stem cells (MSCs) into the joint is an emerging alternative. Adipose-derived MSCs are widely used because fat is easy to harvest. Synovial MSCs, taken from the joint lining, have shown stronger cartilage-forming ability. One proposed explanation is lubricin, a protective joint glycoprotein whose levels fall as OA progresses.

The authors, from the Institute of Science Tokyo, collected synovium (from the suprapatellar pouch) and subcutaneous fat (from the incision site) from 16 OA patients undergoing total knee replacement. The donors were 12 women and 4 men, aged 58 to 87 (median 75). Patients with infection, rheumatoid arthritis, or revision surgery were excluded. MSCs were isolated by collagenase digestion and expanded. Passage 2 cells from each tissue were seeded at 5000 cells/cm² in six replicate wells per donor and cultured for 48 hours. Lubricin in the supernatant was measured by ELISA. For 11 donors the concentrations were measured directly. For the other 5, cell counts were taken and lubricin was normalized to cell number. The team also tested MSC identity by flow cytometry and trilineage differentiation (cartilage, fat, bone). They looked for correlations between synovial MSC lubricin output and age, CRP, white blood cell count, knee pain (numerical rating scale), macroscopic synovial redness and hyperplasia, and Krenn's synovitis score.

In the 11 directly measured donors, synovial MSCs secreted significantly more lubricin than adipose MSCs overall (p = 0.014, Wilcoxon matched-pairs test), with higher output in 8 of the 11 donors. In the 5 donors with cell-number normalization, synovial MSCs secreted more lubricin than adipose MSCs in every donor. Those 5 were described only descriptively because the sample was too small for statistics. Representative synovial and adipose MSC preparations met standard MSC identity criteria. Lubricin secretion by synovial MSCs showed no correlation with age, inflammatory markers, pain scores, or synovial inflammation.

The results give the first direct measurement, to the authors' knowledge, of secreted lubricin protein from synovial versus adipose MSCs. Earlier work relied mainly on gene expression or the proportion of cells staining for lubricin. They support the idea that lubricin production may help explain the cartilage-protective edge of synovial MSCs seen in animal and early human studies, and they may help guide cell-source selection for OA cell therapy.

Several caveats apply. This is a small in vitro study in OA patients at the time of knee replacement, and it did not test whether the extra lubricin yields clinical benefit. Synovial MSCs did not outperform adipose MSCs in every donor, and the lack of correlation with clinical measures means donor-level variability remains unexplained.