Abstract
BackgroundPrevious basic research and clinical studies examined the effects of mesenchymal stem cells (MSCs) on regeneration and maintenance of articular cartilage. However, our pilot study suggested that MSCs are more effective at suppressing inflammation and pain rather than promoting cartilage regeneration in osteoarthritis. Adipose tissue is considered a useful source of MSCs; it can be harvested easily in larger quantities compared with the bone marrow. The present study was designed to evaluate the anti-inflammatory, analgesic, and regenerative effects of intra-articularly injected processed lipoaspirate (PLA) cells (containing adipose-derived MSCs) on degenerative cartilage in a rat osteoarthritis model.MethodsPLA cells were isolated from subcutaneous adipose tissue of 12-week-old female Sprague-Dawley rats. Osteoarthritis was induced by injection of monoiodoacetate (MIA). Each rat received 1 × 106 MSCs into the joint at day 7 (early injection group) and day 14 (late injection group) post-MIA injection. At 7, 14, 21 days after MIA administration, pain was assessed by immunostaining and western blotting of dorsal root ganglion (DRG). Cartilage quality was assessed macroscopically and by safranin-O and H&E staining, and joint inflammation was assessed by western blotting of the synovium.ResultsThe early injection group showed less cartilage degradation, whereas the late injection group showed cartilage damage similar to untreated OA group. The relative expression level of CGRP protein in DRG neurons was significantly lower in the two treatment groups, compared with the untreated group.ConclusionsIntra-articular injection of PLA cells prevented degenerative changes in the early injection group, but had little effect in promoting cartilage repair in the late injection group. Interestingly, intra-articular injection of PLA cells resulted in suppression of inflammation and pain in both OA groups. Further studies are needed to determine the long-term effects of intra-articular injection of PLA cells in osteoarthritis.
Highlights
Previous basic research and clinical studies examined the effects of mesenchymal stem cells (MSCs) on regeneration and maintenance of articular cartilage
Flow cytometry was used to determine the phenotypic profile of the rat processed lipoaspirate (PLA) cells: 99.4% of these cells were positive for CD29 (Fig. 2a), 99.0% positive for CD90 (Fig. 2b), 99.7% negative for CD31 (Fig. 2c), and 100% negative for isotype control (Fig. 2d)
Effect of intraarticular injection of PLA cells on cartilage degradation In the untreated OA group, cartilage erosion was observed at 2 weeks, and bone destruction became evident at 3 weeks with further progression at 4 weeks (Fig. 3a)
Summary
Previous basic research and clinical studies examined the effects of mesenchymal stem cells (MSCs) on regeneration and maintenance of articular cartilage. The present study was designed to evaluate the anti-inflammatory, analgesic, and regenerative effects of intra-articularly injected processed lipoaspirate (PLA) cells (containing adipose-derived MSCs) on degenerative cartilage in a rat osteoarthritis model. Total knee arthroplasty and tibial osteotomy are currently performed worldwide to eliminate knee pain and improve joint function, knee OA is often managed conservatively with medications, intra-articular injections, brace, fomentation and physiotherapy. In this context, it is desirable to develop effective therapies for knee OA that are less invasive, inexpensive, safe, and produce rapid and long-lasting effects. Cartilage tissues have limited intrinsic capacity for repair and no medications have yet been developed that can achieve durable modification of OA progression
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