Carlotta Perucca Orfei1, Angelo Boffa2, Yosef Sourugeon3, Lior Laver4,5,6, Jérémy Magalon7,8,9, Mikel Sánchez10,11, Thomas Tischer12, Giuseppe Filardo13,14,15, Laura de Girolamo1. 1. IRCCS Istituto Ortopedico Galeazzi, Laboratorio di Biotecnologie Applicate all'Ortopedia, Milan, Italy. 2. Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. angeloboffa@libero.it. 3. Rambam Health Care Campus, Haifa, Israel. 4. Department of Orthopaedics, Hillel Yaffe Medical Center (HYMC), Hadera, Israel. 5. Arthrosport Clinic, Tel-Aviv, Israel. 6. Technion University Hospital (Israel Institute of Technology) - Rappaport Faculty of Medicine, Haifa, Israel. 7. Cell Therapy Laboratory, Hôpital De La Conception, AP-HM, Marseille, France. 8. INSERM, NRA, C2VN, Aix Marseille Univ, Marseille, France. 9. SAS Remedex, Marseille, France. 10. Arthroscopic Surgery Unit, Hospital Vithas Vitoria, Vitoria-Gasteiz, Spain. 11. Advanced Biological Therapy Unit, Hospital Vithas Vitoria, Vitoria-Gasteiz, Spain. 12. Department of Orthopaedic Surgery, University of Rostock, Rostock, Germany. 13. Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. 14. Service of Orthopaedics and Traumatology, Department of Surgery, EOC, Lugano, Switzerland. 15. Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland.
Abstract
PURPOSE: The aim of this systematic review was to determine if adipose tissue-derived cell-based injectable therapies can induce disease-modifying effects in joints affected by osteoarthritis (OA). METHODS: A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical studies comparing injectable adipose-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE's tool. RESULTS: Seventy-one studies were included (2,086 animals) with an increasing publication trend over time. Expanded cells were used in 65 studies, 3 studies applied point of care products, and 3 studies investigated both approaches. Overall, 48 out of 51 studies (94%) reported better results with adipose-derived products compared to OA controls, with positive findings in 17 out of 20 studies (85%) in macroscopic, in 37 out of 40 studies (93%) in histological, and in 22 out of 23 studies (96%) in immunohistochemical evaluations. Clinical and biomarker evaluations showed positive results in 14 studies out of 18 (78%) and 12 studies out of 14 (86%), while only 9 studies out of 17 (53%) of the imaging evaluations were able to detect differences versus controls. The risk of bias was low in 38% of items, unclear in 51%, and high in (11%). CONCLUSION: The current preclinical models document consistent evidence of disease-modifying effects of adipose-derived cell-based therapies for the treatment of OA. The high heterogeneity of the published studies highlights the need for further targeted research to provide recommendations on the optimal methodologies for a more effective application of these injective therapies for the treatment of OA in clinical practice. LEVEL OF EVIDENCE: II.
PURPOSE: The aim of this systematic review was to determine if adipose tissue-derived cell-based injectable therapies can induce disease-modifying effects in joints affected by osteoarthritis (OA). METHODS: A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical studies comparing injectable adipose-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE's tool. RESULTS: Seventy-one studies were included (2,086 animals) with an increasing publication trend over time. Expanded cells were used in 65 studies, 3 studies applied point of care products, and 3 studies investigated both approaches. Overall, 48 out of 51 studies (94%) reported better results with adipose-derived products compared to OA controls, with positive findings in 17 out of 20 studies (85%) in macroscopic, in 37 out of 40 studies (93%) in histological, and in 22 out of 23 studies (96%) in immunohistochemical evaluations. Clinical and biomarker evaluations showed positive results in 14 studies out of 18 (78%) and 12 studies out of 14 (86%), while only 9 studies out of 17 (53%) of the imaging evaluations were able to detect differences versus controls. The risk of bias was low in 38% of items, unclear in 51%, and high in (11%). CONCLUSION: The current preclinical models document consistent evidence of disease-modifying effects of adipose-derived cell-based therapies for the treatment of OA. The high heterogeneity of the published studies highlights the need for further targeted research to provide recommendations on the optimal methodologies for a more effective application of these injective therapies for the treatment of OA in clinical practice. LEVEL OF EVIDENCE: II.
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