Pietro Randelli1,2, Laura de Girolamo3, Marco Viganò3, Gaia Lugano3, Carlotta Perucca Orfei4, Alessandra Menon1,2, Enrico Ragni3, Alessandra Colombini3, Paola De Luca3. 1. Laboratory of Applied Biomechanics, Department of Biomedical Sciences for Health, Università degli Studi di Milano, Via Mangiagalli 31, 20133, Milan, Italy. 2. 1° Clinica Ortopedica, ASST Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO, Piazza Cardinal Ferrari 1, 20122, Milan, Italy. 3. Orthopedics Biotechnology Lab, IRCCS Istituto Ortopedico Galeazzi, via Riccardo Galeazzi 4, 20161, Milan, Italy. 4. Orthopedics Biotechnology Lab, IRCCS Istituto Ortopedico Galeazzi, via Riccardo Galeazzi 4, 20161, Milan, Italy. carlotta.perucca@grupposandonato.it.
Abstract
PURPOSE: Rotator cuff tears are common musculoskeletal disorders, and surgical repair is characterized by a high rate of re-tear. Regenerative medicine strategies, in particular mesenchymal stem cell-based therapies, have been proposed to enhance tendon healing and reduce the re-tear rate. Autologous microfragmented adipose tissue (μFAT) allows for the clinical application of cell therapies and showed the ability to improve tenocyte proliferation and viability in previous in vitro assessments. The hypothesis of this study is that μFAT paracrine action would reduce the catabolic and inflammatory marker expression in tendon cells (TCs) derived from injured supraspinatus tendon (SST). METHODS: TCs derived from injured SST were co-cultured with autologous μFAT in transwell for 48 h. Metabolic activity, DNA content, the content of soluble mediators in the media, and the gene expression of tendon-specific, inflammatory, and catabolic markers were analyzed. RESULTS: μFAT-treated TCs showed a reduced expression of PTGS2 and MMP-3 with respect to untreated controls. Increased IL-1Ra, VEGF, and IL-6 content were observed in the media of μFAT-treated samples, in comparison with untreated TCs. CONCLUSION: μFAT exerted an anti-inflammatory action on supraspinatus tendon cells in vitro through paracrine action, resulting in the reduction of catabolic and inflammatory marker expression. These observations potentially support the use of μFAT as adjuvant therapy in the treatment of rotator cuff disease.
PURPOSE: Rotator cuff tears are common musculoskeletal disorders, and surgical repair is characterized by a high rate of re-tear. Regenerative medicine strategies, in particular mesenchymal stem cell-based therapies, have been proposed to enhance tendon healing and reduce the re-tear rate. Autologous microfragmented adipose tissue (μFAT) allows for the clinical application of cell therapies and showed the ability to improve tenocyte proliferation and viability in previous in vitro assessments. The hypothesis of this study is that μFAT paracrine action would reduce the catabolic and inflammatory marker expression in tendon cells (TCs) derived from injured supraspinatus tendon (SST). METHODS:TCs derived from injured SST were co-cultured with autologous μFAT in transwell for 48 h. Metabolic activity, DNA content, the content of soluble mediators in the media, and the gene expression of tendon-specific, inflammatory, and catabolic markers were analyzed. RESULTS: μFAT-treated TCs showed a reduced expression of PTGS2 and MMP-3 with respect to untreated controls. Increased IL-1Ra, VEGF, and IL-6 content were observed in the media of μFAT-treated samples, in comparison with untreated TCs. CONCLUSION: μFAT exerted an anti-inflammatory action on supraspinatus tendon cells in vitro through paracrine action, resulting in the reduction of catabolic and inflammatory marker expression. These observations potentially support the use of μFAT as adjuvant therapy in the treatment of rotator cuff disease.
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