Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial
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| Název: | Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial |
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| Autoři: | Pers, Yves-Marie, Rackwitz, Lars, Ferreira, Rosanna, Pullig, Oliver, Delfour, Christophe, Barry, Frank, Sensebe, Luc, Casteilla, Louis, Fleury, Sandrine, Bourin, Philippe, Noël, Danièle, Canovas, François, Cyteval, Catherine, Lisignoli, Gina, Schrauth, Joachim, Haddad, Daniel, Domergue, Sophie, Noeth, Ulrich, Jorgensen, Christian |
| Přispěvatelé: | Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Lapeyronie CHU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Julius-Maximilians-Universität Würzburg = University of Würzburg Würsburg, Germany (JMU), Département de Rhumatologie Hôpital Lapeyronie - CHU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), CHU Montpellier = Montpellier University Hospital, National University of Ireland Galway (NUI Galway), Établissement Français du Sang Alpes-Méditerranée (EFS Alpes-Méditerranée), STROMALab, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), EFS, Istituto Ortopedico Rizzoli Bologna, Hôpital Gui de Chauliac CHU Montpellier, The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement 241719. Work in the laboratory INSERM U844 was also supported by the Inserm Institute, the University of Montpellier, and the Agence Nationale pour la Recherche for support of the national infrastructure: “ECELLFRANCE: Development of a national adult mesenchymal stem cell based therapy platform., ANR-11-INBS-0005,ECELLFRANCE,Développement d'une Plateforme Nationale pour la médecine régénératrice(2011), European Project: 241719,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,ADIPOA(2010) |
| Zdroj: | ISSN: 2157-6564. |
| Informace o vydavateli: | CCSD Wiley |
| Rok vydání: | 2016 |
| Sbírka: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| Témata: | Osteoarthritis, Phase I clinical trial, Regenerative medicine, Therapeutic potential, Adipose mesenchymal stromal cells, Intra-articular injection, MESH: Adipose Tissue / cytology, Adipose Tissue / transplantation, Aged, Cell Count, Female, Humans, Injections, Intra-Articular, Male, Mesenchymal Stem Cell Transplantation* / adverse effects, Mesenchymal Stem Cell Transplantation* / methods, Mesenchymal Stem Cells / cytology, Middle Aged, Knee / pathology, Knee / therapy, Severity of Illness Index, Treatment Outcome, [SDV]Life Sciences [q-bio] |
| Popis: | International audience ; Osteoarthritis x Adipose mesenchymal stromal cells x Intra-articular injection x Therapeutic potential x Regenerative medicine x Phase I clinical trial ABSTRACT Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 3 10 6 cells), medium dose (10 3 10 6), and high dose (50 3 10 6). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intraarticular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy. |
| Druh dokumentu: | article in journal/newspaper |
| Jazyk: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/27217345; info:eu-repo/grantAgreement/EC/FP7/241719/EU/ADIPOSE DERIVED STROMAL CELLS FOR OSTEOARTHRITIS/ADIPOA; PUBMED: 27217345; PUBMEDCENTRAL: PMC4922848 |
| DOI: | 10.5966/sctm.2015-0245 |
| Dostupnost: | https://hal.umontpellier.fr/hal-01834263 https://hal.umontpellier.fr/hal-01834263v1/document https://hal.umontpellier.fr/hal-01834263v1/file/IRMB%2057_p35_Adipose%20Mesenchymal%20Stromal%20Cell-BasedTherapy%20for%20Severe%20Osteoarthritis%20of%20the%20Knee_sctm_20150245.pdf https://doi.org/10.5966/sctm.2015-0245 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| Přístupové číslo: | edsbas.C10BAF8D |
| Databáze: | BASE |
Nájsť tento článok vo Web of Science | Abstrakt: | International audience ; Osteoarthritis x Adipose mesenchymal stromal cells x Intra-articular injection x Therapeutic potential x Regenerative medicine x Phase I clinical trial ABSTRACT Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 3 10 6 cells), medium dose (10 3 10 6), and high dose (50 3 10 6). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intraarticular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy. |
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| DOI: | 10.5966/sctm.2015-0245 |