期刊
MOLECULAR THERAPY
卷 29, 期 2, 页码 804-821出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2020.10.026
关键词
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资金
- Velux Stiftung [976a]
- La Caixa Health [HR17-00231]
- Ministerio de Ciencia e Innovacion [BFU2017-86760-P]
- AGAUR grant from the Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement de la Generalitat de Catalunya [2017 SGR 689]
- Subprograma Estatal de Formacion del Ministerio de Economia y Competitividad [BES-2015-072802, BES-2015-075805]
- Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement de la Generalitat de Catalunya [2018FI_B_00637]
- Fondo Social Europeo (FSE)
- Spanish Ministry of Science and Innovation
- Centro de Excelencia Severo Ochoa
- CERCA Programme/Generalitat de Catalunya
This study demonstrates that chemokines released from degenerating retinae can drive the migration of transplanted stem cells, and overexpression of chemokine receptors can improve the effectiveness of stem cell therapy by enhancing rescue of cell death and preserving electrophysiological function.
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.
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