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Hsa-miR-520d Converts Fibroblasts into CD105+ Populations

BACKGROUND: We have previously shown that hsa-miR-520d-5p can convert cancer cells into induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) via a dedifferentiation by a demethylation mechanism. METHODS: We tested the effect of miR-520d-5p on human fibroblasts to determine whether...

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Autores principales: Ishihara, Yoshitaka, Tsuno, Satoshi, Kuwamoto, Satoshi, Yamashita, Taro, Endo, Yusuke, Hasegawa, Junichi, Miura, Norimasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269822/
https://www.ncbi.nlm.nih.gov/pubmed/25303886
http://dx.doi.org/10.1007/s40268-014-0064-6
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author Ishihara, Yoshitaka
Tsuno, Satoshi
Kuwamoto, Satoshi
Yamashita, Taro
Endo, Yusuke
Hasegawa, Junichi
Miura, Norimasa
author_facet Ishihara, Yoshitaka
Tsuno, Satoshi
Kuwamoto, Satoshi
Yamashita, Taro
Endo, Yusuke
Hasegawa, Junichi
Miura, Norimasa
author_sort Ishihara, Yoshitaka
collection PubMed
description BACKGROUND: We have previously shown that hsa-miR-520d-5p can convert cancer cells into induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) via a dedifferentiation by a demethylation mechanism. METHODS: We tested the effect of miR-520d-5p on human fibroblasts to determine whether it could be safely used in normal cells for future clinical therapeutic applications. After we transfected the microRNA into fibroblasts, we analyzed the phenotypic changes, gene expression levels, and stemness induction in vitro, and we evaluated tumor formation in an in vivo xenograft model. RESULTS: The transfected fibroblasts turned into CD105+ cell populations, survived approximately 24 weeks, and exhibited increases in both the collagen-producing ability and in differentiation. Combinatorial transfection of small interfering RNAs for miR-520d-5p target genes (ELAVL2, GATAD2B, and TEAD1) produced similar results to miR-520d-5p transfection. These molecules converted normal cells into MSCs and not iPSCs. CONCLUSIONS: In vitro data indicate the potent usefulness of this small molecule as a therapeutic biomaterial in normal cells and cancer cells because CD105+ cells never converted to iPSCs despite repeated transfections and all types of transfectants lost their tumorigenicity. This maintenance of a benign state following miR-520d-5p transfection appears to be caused by p53 upregulation. We conclude that miR-520d-5p may be a useful biomaterial at an in vitro level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40268-014-0064-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-42698222014-12-22 Hsa-miR-520d Converts Fibroblasts into CD105+ Populations Ishihara, Yoshitaka Tsuno, Satoshi Kuwamoto, Satoshi Yamashita, Taro Endo, Yusuke Hasegawa, Junichi Miura, Norimasa Drugs R D Original Research Article BACKGROUND: We have previously shown that hsa-miR-520d-5p can convert cancer cells into induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) via a dedifferentiation by a demethylation mechanism. METHODS: We tested the effect of miR-520d-5p on human fibroblasts to determine whether it could be safely used in normal cells for future clinical therapeutic applications. After we transfected the microRNA into fibroblasts, we analyzed the phenotypic changes, gene expression levels, and stemness induction in vitro, and we evaluated tumor formation in an in vivo xenograft model. RESULTS: The transfected fibroblasts turned into CD105+ cell populations, survived approximately 24 weeks, and exhibited increases in both the collagen-producing ability and in differentiation. Combinatorial transfection of small interfering RNAs for miR-520d-5p target genes (ELAVL2, GATAD2B, and TEAD1) produced similar results to miR-520d-5p transfection. These molecules converted normal cells into MSCs and not iPSCs. CONCLUSIONS: In vitro data indicate the potent usefulness of this small molecule as a therapeutic biomaterial in normal cells and cancer cells because CD105+ cells never converted to iPSCs despite repeated transfections and all types of transfectants lost their tumorigenicity. This maintenance of a benign state following miR-520d-5p transfection appears to be caused by p53 upregulation. We conclude that miR-520d-5p may be a useful biomaterial at an in vitro level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40268-014-0064-6) contains supplementary material, which is available to authorized users. Springer International Publishing 2014-10-11 2014-12 /pmc/articles/PMC4269822/ /pubmed/25303886 http://dx.doi.org/10.1007/s40268-014-0064-6 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by-nc/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Research Article
Ishihara, Yoshitaka
Tsuno, Satoshi
Kuwamoto, Satoshi
Yamashita, Taro
Endo, Yusuke
Hasegawa, Junichi
Miura, Norimasa
Hsa-miR-520d Converts Fibroblasts into CD105+ Populations
title Hsa-miR-520d Converts Fibroblasts into CD105+ Populations
title_full Hsa-miR-520d Converts Fibroblasts into CD105+ Populations
title_fullStr Hsa-miR-520d Converts Fibroblasts into CD105+ Populations
title_full_unstemmed Hsa-miR-520d Converts Fibroblasts into CD105+ Populations
title_short Hsa-miR-520d Converts Fibroblasts into CD105+ Populations
title_sort hsa-mir-520d converts fibroblasts into cd105+ populations
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269822/
https://www.ncbi.nlm.nih.gov/pubmed/25303886
http://dx.doi.org/10.1007/s40268-014-0064-6
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