The chemokine receptors Ccr5 and Cxcr6 enhance migration of mesenchymal stem cells into the degenerating retina

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• dc.contributor.author Pesaresi, Martina
• dc.contributor.author Bonilla-Pons, Sergi A.
• dc.contributor.author Sebastián Pérez, Rubén
• dc.contributor.author Di Vicino, Umberto
• dc.contributor.author Alcoverro-Bertran, Marc
• dc.contributor.author Michael, Ralph
• dc.contributor.author Cosma, Maria Pia
• dc.date.accessioned 2021-03-15T11:48:51Z
• dc.date.issued 2021
• dc.description.abstract Cell therapy approaches hold great potential for treating retinopathies, which are currently incurable. This study addresses the problem of inadequate migration and integration of transplanted cells into the host retina. To this end, we have identified the chemokines that were most upregulated during retinal degeneration and that could chemoattract mesenchymal stem cells (MSCs). The results were observed using a pharmacological model of ganglion/amacrine cell degeneration and a genetic model of retinitis pigmentosa, from both mice and human retinae. Remarkably, MSCs overexpressing Ccr5 and Cxcr6, which are receptors bound by a subset of the identified chemokines, displayed improved migration after transplantation in the degenerating retina. They also led to enhanced rescue of cell death and to preservation of electrophysiological function. Overall, we show that chemokines released from the degenerating retinae can drive migration of transplanted stem cells, and that overexpression of chemokine receptors can improve cell therapy-based regenerative approaches.
• dc.description.sponsorship This work was supported by Velux Stiftung (976 a to M.P.C.), La Caixa Health (HR17-00231), the Ministerio de Ciencia e Innovación, (BFU2017-86760-P to M.P.C.) (AEI/FEDER, UE), the AGAUR grant from Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya, (2017 SGR 689 to M.P.C.), the subprograma estatal de Formación del Ministerio de Economía y Competitividad ref. BES-2015-075802 (to M.P.) and ref. BES-2015-075805 (to S.A.B.-P.), the Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement de la Generalitat de Catalunya ref. 2018FI_B_00637 (to R.S.-P.), and the co‐finance of Fondo Social Europeo (FSE to R.S.-P.). We acknowledge support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme / Generalitat de Catalunya
• dc.format.mimetype application/pdf
• dc.identifier.citation Pesaresi M, Bonilla-Pons SA, Sebastian-Perez R, Vicino U, Alcoverro-Bertran M. Michael R et al. The chemokine receptors Ccr5 and Cxcr6 enhance migration of mesenchymal stem cells into the degenerating retina. Mol Ther. 2021 Feb 3;29(2):804-821. DOI: 10.1016/j.ymthe.2020.10.026
• dc.identifier.doi http://dx.doi.org/10.1016/j.ymthe.2020.10.026
• dc.identifier.issn 1525-0016
• dc.identifier.uri http://hdl.handle.net/10230/46779
• dc.language.iso eng
• dc.publisher Science Direct
• dc.relation.ispartof Molecular Therapy. 2021 Feb 3;29(2):804-821
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BES-2015-075802
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BES-2015-075805
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86760-P
• dc.rights © 2020 The American Society of Gene and Cell Therapy
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Retina
• dc.subject.other Genètica
• dc.title The chemokine receptors Ccr5 and Cxcr6 enhance migration of mesenchymal stem cells into the degenerating retina
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion