Reiterative infusions of MSCs improve pediatric osteogenesis imperfecta eliciting a pro-osteogenic paracrine response: TERCELOI clinical trial
dc.contributor.author | Infante, Arantza | |
dc.contributor.author | Gener, Blanca | |
dc.contributor.author | Vázquez, Miguel | |
dc.contributor.author | Olivares, Nerea | |
dc.contributor.author | Arrieta, Arantza | |
dc.contributor.author | Grau, Gema | |
dc.contributor.author | Llano, Isabel | |
dc.contributor.author | Madero, Luis | |
dc.contributor.author | Bueno, Ana Maria | |
dc.contributor.author | Sagastizabal, Belén | |
dc.contributor.author | Gerovska, Daniela | |
dc.contributor.author | Araúzo Bravo, Marcos J. | |
dc.contributor.author | Astigarraga Aguirre, María Iciar | |
dc.contributor.author | Rodríguez López, Clara Isabel | |
dc.date.accessioned | 2021-02-26T13:30:49Z | |
dc.date.available | 2021-02-26T13:30:49Z | |
dc.date.issued | 2021-01-12 | |
dc.identifier.citation | Clinical and Translational Medicine 11 : (2021) // Article ID e265 | es_ES |
dc.identifier.issn | 2001-1326 | |
dc.identifier.uri | http://hdl.handle.net/10810/50347 | |
dc.description.abstract | Background Osteogenesis imperfecta (OI) is a rare genetic disease characterized by bone fragility, with a wide range in the severity of clinical manifestations. The majority of cases are due to mutations in the COL1A1 or COL1A2 genes, which encode type I collagen. Mesenchymal stem cells (MSCs), as the progenitors of the osteoblasts, the main type I collagen secreting cell type in the bone, have been proposed and tested as an innovative therapy for OI with promising but transient outcomes. Methods To overcome the short-term effect of MSCs therapy, we performed a phase I clinical trial based on reiterative infusions of histocompatible MSCs, administered in a 2.5-year period, in two pediatric patients affected by severe and moderate OI. The aim of this study was to assess the safety and effectiveness of this cell therapy in nonimmunosuppressed OI patients. The host response to MSCs was studied by analyzing the sera from OI patients, collected before, during, and after the cell therapy. Results We first demonstrated that the sequential administration of MSCs was safe and improved the bone parameters and quality of life of OI patients along the cell treatment plus 2-year follow-up period. Moreover, the study of the mechanism of action indicated that MSCs therapy elicited a pro-osteogenic paracrine response in patients, especially noticeable in the patient affected by severe OI. Conclusions Our results demonstrate the feasibility and potential of reiterative MSCs infusion for two pediatric OI and highlight the paracrine response shown by patients as a consequence of MSCs treatment. | es_ES |
dc.description.sponsorship | We are grateful to the patients affected by OI and their families, and to the AHUCE Foundation, especially to its director Ms Julia Piniella, for the support during the clinical trial. We also thank Dr ME Fernandez-Santos (GM-Cell Production Unit, IiSGM) for her expertise in the cell production, Jose Ignacio Pijoan Zubizarreta (Clinical Epidemiology Unit of Cruces University Hospital) for the overall support provided to the project, and Natale Imaz (Biocruces Bizkaia Health Research Institute) for providing the data and safety monitoring of the clinical trial. We are indebted to all the health professionals from Cruces University Hospital, especially to the Pediatric Intensive Care Unit for their participation. This study was funded by the Spanish Ministry of Health through the call for independent clinical trials projects "EC10-219," Instituto de Salud Carlos III through the project "PI15/00820" (Co-funded by European Regional Development Fund; "A way to make Europe"), Bioef-EiTB maratoia (BIO14/TP/007), and the AHUCE Foundation. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | cell therapy | es_ES |
dc.subject | mesenchymal stem cell | es_ES |
dc.subject | paracrine mechanism of action | es_ES |
dc.subject | regenerative medicine | es_ES |
dc.title | Reiterative infusions of MSCs improve pediatric osteogenesis imperfecta eliciting a pro-osteogenic paracrine response: TERCELOI clinical trial | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/10.1002/ctm2.265 | es_ES |
dc.identifier.doi | 10.1002/ctm2.265 | |
dc.departamentoes | Pediatría | es_ES |
dc.departamentoeu | Pediatria | es_ES |
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Except where otherwise noted, this item's license is described as The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited