Autologous Adipose-Derived Mesenchymal Stem Cells Combined with Shockwave Therapy Synergistically Ameliorates the Osteoarthritic Pathological Factors in Knee Joint

Abstract

Adipose-derived mesenchymal stem cells (ADSCs) and shockwave (SW) therapy have been shown to exert a chondroprotective effect for osteoarthritis (OA). The results of this study demonstrated that autologous ADSCs had dose-dependent and synergistic effects with SW therapy (0.25 mJ/mm2 with 800 impulses) in OA rat knee joint. Autologous, high-dose 2 × 106 ADSCs (ADSC2 group) combined with SW therapy significantly increased the bone volume, trabecular thickness, and trabecular number among in the treatment groups. ADSC2 combined with SW therapy significantly reduced the synovitis score and OARSI score in comparison with other treatments. In the analysis of inflammation-induced extracellular matrix factors of the articular cartilage in OA, the results displayed that ADSC2 combined with SW therapy had a greater than other treatments in terms of reducing tumor necrosis factor-inducible gene (TSG)-6 and proteoglycan (PRG)-4, in addition to increasing tissue inhibitor matrix metalloproteinase (TIMP)-1 and type II collagen. Furthermore, ADSC2 combined with SW therapy significantly reduced the expression of inflammation-induced bone morphogenetic protein (BMP)-2 and BMP-6. Therefore, the results demonstrated that ADSC2 combined with SW therapy had a synergistic effect to ameliorate osteoarthritic pathological factors in OA joints.

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies

“…Seventeen studies evaluated the effects by imaging analysis: nine studies (52.9%) reported significant differences in favour of adipose-derived products, while eight studies observed no differences. In particular, micro-computed tomography (micro-CT) evaluation was performed in six studies, with positive effects in five studies in terms of prevention of cartilage and subchondral bone degeneration and improvement of bone thickness and volume [23][24][25][26][27]. Radiographic evaluation was performed in 6 studies with only one study showing a statistically significant difference in favour of adipose-derived products [28].…”

Adipose-Derived Mesenchymal Stem Cells-Conditioned Medium Modulates the Expression of Inflammation Induced Bone Morphogenetic Protein-2, -5 and -6 as Well as Compared with Shockwave Therapy on Rat Knee Osteoarthritis

“…The SW group animals received SW treatment using an SW device DUOLITH SD1 (STORZ MEDICAL AG, Tägerwilen, Switzerland). A shockwave was applied to the subchondral bone of the medial tibial condyle of the left knee at 0.5 cm below the joint line and 0.5 cm from the medial skin surface [29]. Each knee received 800 pulses of SW at 0.25 mJ/mm 2 energy flux density of 4 Hz.…”

“…Preparation of rat adipose-derived MSCs (ADSCs) was performed as described in our previous study [29,30]. Briefly, rat ADSCs were isolated from subcutaneous adipose tissues of SD rats at 8 weeks of age.…”

“…The method for the identification of rat ADSCs was performed as described in our previous study [29,30]. The spindle-shaped rat ADSCs were cultured after three to five passages, and the specific surface markers were characterized by flow cytometry (BD LSRII, San Jose, CA, USA).…”

“…The spindle-shaped rat ADSCs were cultured after three to five passages, and the specific surface markers were characterized by flow cytometry (BD LSRII, San Jose, CA, USA). Cells were incubated with specific antibodies conjugated with fluorescein isothiocyanate (FITC) or phycoerythrin (PE) against the indicated markers including CD29, CD45, CD90, CD106, RT1a, and RT1b [29].…”