Giuseppe Filardo1, Matilde Tschon2, Milena Fini2, Elizaveta Kon3,4, Francesco Perdisa5, Silvia Brogini2, Carola Cavallo6, Giovanna Desando6, Gianluca Giavaresi2, Brunella Grigolo6, Lucia Martini2, Nicolò Nicoli Aldini2, Alice Roffi1. 1. Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, Bologna, Italy. 2. Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, Bologna, Italy. 3. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele, Milan, Italy. 4. Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, Rozzano, 20089, Milan, Italy. 5. SC Chirurgia Protesica e dei Reimpianti d'Anca e di Ginocchio, IRCCS Istituto Ortopedico Rizzoli, Via Pupilli 2, 40136, Bologna, Italy. dr.perdisa@gmail.com. 6. Laboratorio RAMSES, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, Bologna, Italy.
Abstract
PURPOSE: The aim of this study was to compare three procedures to exploit adipose-derived cells for the treatment of osteoarthritis (OA) in a preclinical model, to understand their therapeutic potential and identify the most suitable approach for the clinical application. METHODS: Biological samples from adipose tissue, processed by mechanical micro-fragmentation (MF), enzymatic digestion (SVF) or cell expansion (ADSCs), were first characterized in vitro and then used in vivo in a surgically induced OA rabbit model: Group 1-control group (untreated 12 knees/saline 12 knees), Group 2-MF (24 knees), Group 3-SVF (24 knees), Group 4-ADSCs (24 knees). Macroscopic, histological, histomorphometric, immunohistochemical and blood and synovial fluid analyses were evaluated at 2 and 4 months from the treatments. RESULTS: Samples obtained by the three procedures yielded 85-95% of viable cells. In vivo assessments showed no significant side effects or inflammatory responses after the injection. The macroscopic Hanashi score did not show significant differences among treated groups and controls. The histopathological evaluation of synovial tissues showed lower signs of synovitis for MF, although the semiquantitative analysis (Krenn score) did not reach statistical significance. Instead, MF showed the best results both in terms of qualitative and semi-quantitative evaluations of articular cartilage, with a more uniform staining, a smoother surface and a significantly better Laverty score (p = 0.004). CONCLUSION: MF, SVF, and expanded ADSCs did not elicit significant local or systemic adverse reactions in this preclinical OA model. Among the different methods used to exploit the adipose tissue potential, MF showed the most promising findings in particular in terms of protection of the articular surface from the joint degenerative OA processes. LEVEL OF EVIDENCE: Preclinical animal study.
PURPOSE: The aim of this study was to compare three procedures to exploit adipose-derived cells for the treatment of osteoarthritis (OA) in a preclinical model, to understand their therapeutic potential and identify the most suitable approach for the clinical application. METHODS: Biological samples from adipose tissue, processed by mechanical micro-fragmentation (MF), enzymatic digestion (SVF) or cell expansion (ADSCs), were first characterized in vitro and then used in vivo in a surgically induced OA rabbit model: Group 1-control group (untreated 12 knees/saline 12 knees), Group 2-MF (24 knees), Group 3-SVF (24 knees), Group 4-ADSCs (24 knees). Macroscopic, histological, histomorphometric, immunohistochemical and blood and synovial fluid analyses were evaluated at 2 and 4 months from the treatments. RESULTS: Samples obtained by the three procedures yielded 85-95% of viable cells. In vivo assessments showed no significant side effects or inflammatory responses after the injection. The macroscopic Hanashi score did not show significant differences among treated groups and controls. The histopathological evaluation of synovial tissues showed lower signs of synovitis for MF, although the semiquantitative analysis (Krenn score) did not reach statistical significance. Instead, MF showed the best results both in terms of qualitative and semi-quantitative evaluations of articular cartilage, with a more uniform staining, a smoother surface and a significantly better Laverty score (p = 0.004). CONCLUSION: MF, SVF, and expanded ADSCs did not elicit significant local or systemic adverse reactions in this preclinical OA model. Among the different methods used to exploit the adipose tissue potential, MF showed the most promising findings in particular in terms of protection of the articular surface from the joint degenerative OA processes. LEVEL OF EVIDENCE: Preclinical animal study.
Authors: L Danisovic; L Oravcova; L Krajciova; Z Varchulova Novakova; M Bohac; I Varga; J Vojtassak Journal: J Physiol Pharmacol Date: 2017-02 Impact factor: 3.011
Authors: Paul Girard; Joelle Dulong; Jerome Duisit; Camille Mocquard; Simon Le Gallou; Benoit Chaput; Elise Lupon; Eric Watier; Audrey Varin; Karin Tarte; Nicolas Bertheuil Journal: Front Bioeng Biotechnol Date: 2022-09-13