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Micro-fragmentation is a valid alternative to cell expansion and enzymatic digestion of adipose tissue for the treatment of knee osteoarthritis: a comparative preclinical study

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Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

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.

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Funding

This study was funded by the Project “Adipose-derived mesenchymal stem cells as a new minimally invasive regenerative treatment to target early osteoarthritis: from preclinical procedure selection to clinical application in a randomised double-blinded controlled trial” (project code: RF-2011–02352638).

Author information

Author notes

  1. Giuseppe Filardo and Matilde Tschon equally contributed to this work.

  2. Milena Fini and Elizaveta Kon equally contributed to this work.

Authors and Affiliations

  1. Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, Bologna, Italy

    Giuseppe Filardo & Alice Roffi

  2. Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, Bologna, Italy

    Matilde Tschon, Silvia Brogini, Gianluca Giavaresi, Lucia Martini, Nicolò Nicoli Aldini & Milena Fini

  3. SC Chirurgia Protesica e dei Reimpianti d’Anca e di Ginocchio, IRCCS Istituto Ortopedico Rizzoli, Via Pupilli 2, 40136, Bologna, Italy

    Francesco Perdisa

  4. Laboratorio RAMSES, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, Bologna, Italy

    Carola Cavallo, Giovanna Desando & Brunella Grigolo

  5. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele, Milan, Italy

    Elizaveta Kon

  6. Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, Rozzano, 20089, Milan, Italy

    Elizaveta Kon

Authors
  1. Giuseppe Filardo
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Corresponding author

Correspondence to Francesco Perdisa.

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All Authors confirm they have no Conflict of interests related to the present paper.

Ethical approval

This in vivo study was performed complying with the European and Italian Law on animal experiments, after the approvals of the research protocol by the Ethical Committee and Animal Welfare Body of IRCCS Istituto Ortopedico Rizzoli and by the Italian Ministry of Health (Authorization No. 862/2015-PR) in agreement with Italian (Legislative Decree 26/2014) and EU regulations (Directive 2010/63/EU on the protection of animals used for scientific purposes).

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Filardo, G., Tschon, M., Perdisa, F. et al. Micro-fragmentation is a valid alternative to cell expansion and enzymatic digestion of adipose tissue for the treatment of knee osteoarthritis: a comparative preclinical study. Knee Surg Sports Traumatol Arthrosc 30, 773–781 (2022). https://doi.org/10.1007/s00167-020-06373-y

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