Figure 5.

Human sTNFR-transduced hMSCs reduced joint inflammation in immunodeficient and immunocompetent arthritic rodent models. (A): AbIA. BalbC/SCID mice were i.m. injected with 4 × 10⁶ untransduced hMSCs or hsTNFR-transduced hMSCs (cellular injection IM in schematic) 7 days before arthritic induction. To initiate arthritis, 300 μl of anticollagen type II monoclonal antibody cocktail (Ab in schematic) was i.v. infused into the mice followed 2 days later by an LPS challenge (50 μg per mouse, i.p.; LPS in schematic). The thickness of hind paws was measured with an electronic calibrator two to three times per week, and the data were plotted as percentages of naïve, untransduced hMSCs (n = 10). (B): CIA. Fischer rats were immunized s.c. with mouse collagen II (50 mg) 30 days before the initiation of arthritis (CII Antigen in schematic). Seven days before arthritis induction, 4 × 10⁶ untransduced hMSCs or hsTNFR-transduced hMSCs, etanercept (4 mg/kg, injected twice per week), or dexamethasone (0.25 mg) was i.p. injected (Treatment in schematic). Arthritic induction was initiated by the injection of mouse collagen II (0.5 mg in 50 μl of phosphate-buffered saline [PBS]) into the right knee joint cavity (CII Antigen Inject Knee in schematic); for an internal comparison, PBS (50 μl) was injected into the left knee joint cavity. The swelling (measured with an electronic calibrator) of the right knee was compared with that of the left knee, and the ratio was plotted over time for each of the treatments (n = 10). Abbreviations: Ab, antibody; AbIA, antibody-induced arthritis; CIA, collagen-induced arthritis; Cll, collagen; hMSC, human mesenchymal stem cell; hsTNFR, human soluble tumor necrosis factor receptor II; IM, intramuscular; LPS, lipopolysaccharide; Lt, left; Rt, right.