Genetic reprogramming with stem cells regenerates glomerular epithelial podocytes in Alport syndrome

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dc.citation.issueNumber6en_US
dc.citation.journalTitleLife Science Allianceen_US
dc.citation.volumeNumber7en_US
dc.contributor.authorLeBleu, Valerie S.en_US
dc.contributor.authorKanasaki, Keizoen_US
dc.contributor.authorLovisa, Saraen_US
dc.contributor.authorAlge, Joseph L.en_US
dc.contributor.authorKim, Jihaen_US
dc.contributor.authorChen, Yangen_US
dc.contributor.authorTeng, Yingqien_US
dc.contributor.authorGerami-Naini, Behzaden_US
dc.contributor.authorSugimoto, Hikaruen_US
dc.contributor.authorKato, Noritoshien_US
dc.contributor.authorRevuelta, Ignacioen_US
dc.contributor.authorGrau, Nicoleen_US
dc.contributor.authorSleeman, Jonathan P.en_US
dc.contributor.authorTaduri, Gangadharen_US
dc.contributor.authorKizu, Akaneen_US
dc.contributor.authorRafii, Shahinen_US
dc.contributor.authorHochedlinger, Konraden_US
dc.contributor.authorQuaggin, Susan E.en_US
dc.contributor.authorKalluri, Raghuen_US
dc.date.accessioned2024-07-25T20:55:16Zen_US
dc.date.available2024-07-25T20:55:16Zen_US
dc.date.issued2024en_US
dc.description.abstractGlomerular filtration relies on the type IV collagen (ColIV) network of the glomerular basement membrane, namely, in the triple helical molecules containing the α3, α4, and α5 chains of ColIV. Loss of function mutations in the genes encoding these chains (Col4a3, Col4a4, and Col4a5) is associated with the loss of renal function observed in Alport syndrome (AS). Precise understanding of the cellular basis for the patho-mechanism remains unknown and a specific therapy for this disease does not currently exist. Here, we generated a novel allele for the conditional deletion of Col4a3 in different glomerular cell types in mice. We found that podocytes specifically generate α3 chains in the developing glomerular basement membrane, and that its absence is sufficient to impair glomerular filtration as seen in AS. Next, we show that horizontal gene transfer, enhanced by TGFβ1 and using allogenic bone marrow–derived mesenchymal stem cells and induced pluripotent stem cells, rescues Col4a3 expression and revive kidney function in Col4a3-deficient AS mice. Our proof-of-concept study supports that horizontal gene transfer such as cell fusion enables cell-based therapy in Alport syndrome.en_US
dc.identifier.citationLeBleu, V. S., Kanasaki, K., Lovisa, S., Alge, J. L., Kim, J., Chen, Y., Teng, Y., Gerami-Naini, B., Sugimoto, H., Kato, N., Revuelta, I., Grau, N., Sleeman, J. P., Taduri, G., Kizu, A., Rafii, S., Hochedlinger, K., Quaggin, S. E., & Kalluri, R. (2024). Genetic reprogramming with stem cells regenerates glomerular epithelial podocytes in Alport syndrome. Life Science Alliance, 7(6). https://doi.org/10.26508/lsa.202402664en_US
dc.identifier.digitale202402664-fullen_US
dc.identifier.doihttps://doi.org/10.26508/lsa.202402664en_US
dc.identifier.urihttps://hdl.handle.net/1911/117511en_US
dc.language.isoengen_US
dc.publisherEmbo Pressen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleGenetic reprogramming with stem cells regenerates glomerular epithelial podocytes in Alport syndromeen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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