2015 ISAKOS Biennial Congress ePoster #204

Antiinflammatory and Anabolic Effects of Stem Cells For Osteoarthritis: An In Vitro Study

Mario Ferretti, MD, PhD, São Paulo, SP BRAZIL
Eliane Antonioli, PhD, São Paulo, SP BRAZIL
Carla Piccinato, PhD, São Paulo, SP BRAZIL
Helena B. Nader, PhD, São Paulo, SP BRAZIL
Anna C. Goldberg, PhD, São Paulo, SP BRAZIL
Moises Cohen, MD, PhD, Prof., São Paulo, SP BRAZIL

Hospital Israelita Albert Einstein, Sao Paulo, SP, BRAZIL

FDA Status Not Applicable

Summary: Bone Marrow Mesenchymal Stem Cells (BMSCs) were cultured in conjunction with osteoarthritic chondrocytes. Our results have shown that BMSCs are able to increase production of hyaluronan (extracellular matrix) and decrease inflammatory cytokines (IL-6 and IL-8). In conclusion, our in vitro findings show that BMSCs may have a potential therapeutic effect for osteoarthritis.




Bone marrow mesenchymal stem cells (BM-MSCs) are considered a good source for cellular therapy in cartilage repair. But, their potential to repair the extracellular matrix, in an osteoarthritic environment, is still controversial. In osteoarthritis (OA), antiinflammatory action and extracellular matrix production are important steps for cartilage healing. Therefore, the aim of this study was to evaluate the interaction of BM-MSC and OA-chondrocyte on the production of hyaluronan and inflammatory cytokines.
Methods:Autologous bone marrow and cartilage harvested from OA patients undergoing total knee arthroplasty were co-cultured in a transwell system for 3 and 6 days. Hyaluronan and inflammatory cytokines were measured in supernatants by (ELISA) and by flow cytometry. Inflammatory cytokines, Hyaluronan synthase (HAS)-1, 2, and 3 and hyaluronidases (HYAL) -1, 2, and 3 gene expressions were measured by real-time PCR.
Results:BM-MSCs cell count decreased 1.40 fold after 3 days in co-culture with OA chondrocytes compared to BM-MSCs alone (7.6 x104 vs. 10 x104; P=.05) and 2 fold after 6 days (13.5x104 vs. 6x104; P=..001). However, BM-MSCs produced 2 fold more hyaluronan than OA-chondrocytes (2.80 pg/cell vs. 1.5 pg/cell; P=.05) and after 6 days in co-culture increased 2 fold the production of hyaluronan compared to BM-MSCs alone (3.09 pg/cell vs. 1.45 pg/cell; P=.05). BM-MSCs presented higher HAS-1 mRNA expression when compared to chondrocytes (5.2 vs. 0.46; P=.05) and after co-culture with OA-chondrocyte, HAS-1 mRNA expression in BM-MSCs was upregulated (3.7 vs. 26 1.0; P=.05). In contrast, OA-chondrocytes produced more IL-6 than BM-MSCs after both 3 and 6 days (113 ng/cell,238ng/cell vs.14 ng/cell and 25 ng/cell, P=.0001). Similarly, OA-chondrocytes produced also more IL-8 than BM-MSCs (3 days: 130 vs. 9; P=.05 and 6 days: 107 vs. 5; P=.05) but changes were less pronounced. IL-6 production was reduced in co-culture when compared to chondrocytes alone after 3 days (55 ng/cell vs. 113 pg/cell; P=.05) and after 6 days(238 ng/cell vs. 130 ng/cell; P=.05).
Conclusion:Our results show that, in the presence of OA-chondrocytes, BM-MSCs increase hyaluronan production and decrease inflammatory IL-6 and IL-8 cytokines. It suggests that BM-MSCs may be a potential tool for OA regenerative therapy due to capacity to produce extracellular matrix and inhibit inflammatory cytokines.