Development of Novel Mouse Model of Ulcers Induced by Implantation of Magnets

Abstract We developed a novel mouse model of human refractory cutaneous ulcers that more faithfully reflects pathology and evaluated the effects of mixed cell sheets comprising peripheral blood mononuclear cells and fibroblasts, which we previously developed for treating refractory cutaneous ulcers....

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Autores principales:	Yuriko Takeuchi, Koji Ueno, Takahiro Mizoguchi, Makoto Samura, Takasuke Harada, Atsunori Oga, Tomoaki Murata, Tohru Hosoyama, Noriyasu Morikage, Kimikazu Hamano
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d46508a340e443c3b1139c2ccfbaac9e
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spelling	oai:doaj.org-article:d46508a340e443c3b1139c2ccfbaac9e2021-12-02T15:05:41ZDevelopment of Novel Mouse Model of Ulcers Induced by Implantation of Magnets10.1038/s41598-017-05250-y2045-2322https://doaj.org/article/d46508a340e443c3b1139c2ccfbaac9e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05250-yhttps://doaj.org/toc/2045-2322Abstract We developed a novel mouse model of human refractory cutaneous ulcers that more faithfully reflects pathology and evaluated the effects of mixed cell sheets comprising peripheral blood mononuclear cells and fibroblasts, which we previously developed for treating refractory cutaneous ulcers. Model development involved sandwiching the skin between two magnets, one of which was implanted under the skin for 7 consecutive days. This magnet-implanted ulcer model produced persistently large amounts of exudate and induced the infiltration of the ulcer with inflammatory cells. The model mice had a thicker epidermis and impaired transforming growth factor-β (TGF-β) signaling followed by SMAD2 down-regulation, which causes epidermal hyperplasia in chronic ulcers. Impaired TGF-β signaling also occurred in the ulcers of critical limb ischemia patients. Mixed cell implantation in this ulcer model reduced TNF-α and IL-6 levels in the tissues surrounding the mixed cell sheet-treated ulcers compared with controls or mice treated with trafermin (FGF2). Seven days after commencing therapy, the epidermis was thinner in mice treated with the mixed cell sheets than in controls. This model may therefore serve as a clinically relevant model of human ulcers, and our mixed cell sheets may effectively relieve chronic inflammation and inhibit refractoriness mechanisms.Yuriko TakeuchiKoji UenoTakahiro MizoguchiMakoto SamuraTakasuke HaradaAtsunori OgaTomoaki MurataTohru HosoyamaNoriyasu MorikageKimikazu HamanoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuriko Takeuchi Koji Ueno Takahiro Mizoguchi Makoto Samura Takasuke Harada Atsunori Oga Tomoaki Murata Tohru Hosoyama Noriyasu Morikage Kimikazu Hamano Development of Novel Mouse Model of Ulcers Induced by Implantation of Magnets
description	Abstract We developed a novel mouse model of human refractory cutaneous ulcers that more faithfully reflects pathology and evaluated the effects of mixed cell sheets comprising peripheral blood mononuclear cells and fibroblasts, which we previously developed for treating refractory cutaneous ulcers. Model development involved sandwiching the skin between two magnets, one of which was implanted under the skin for 7 consecutive days. This magnet-implanted ulcer model produced persistently large amounts of exudate and induced the infiltration of the ulcer with inflammatory cells. The model mice had a thicker epidermis and impaired transforming growth factor-β (TGF-β) signaling followed by SMAD2 down-regulation, which causes epidermal hyperplasia in chronic ulcers. Impaired TGF-β signaling also occurred in the ulcers of critical limb ischemia patients. Mixed cell implantation in this ulcer model reduced TNF-α and IL-6 levels in the tissues surrounding the mixed cell sheet-treated ulcers compared with controls or mice treated with trafermin (FGF2). Seven days after commencing therapy, the epidermis was thinner in mice treated with the mixed cell sheets than in controls. This model may therefore serve as a clinically relevant model of human ulcers, and our mixed cell sheets may effectively relieve chronic inflammation and inhibit refractoriness mechanisms.
format	article
author	Yuriko Takeuchi Koji Ueno Takahiro Mizoguchi Makoto Samura Takasuke Harada Atsunori Oga Tomoaki Murata Tohru Hosoyama Noriyasu Morikage Kimikazu Hamano
author_facet	Yuriko Takeuchi Koji Ueno Takahiro Mizoguchi Makoto Samura Takasuke Harada Atsunori Oga Tomoaki Murata Tohru Hosoyama Noriyasu Morikage Kimikazu Hamano
author_sort	Yuriko Takeuchi
title	Development of Novel Mouse Model of Ulcers Induced by Implantation of Magnets
title_short	Development of Novel Mouse Model of Ulcers Induced by Implantation of Magnets
title_full	Development of Novel Mouse Model of Ulcers Induced by Implantation of Magnets
title_fullStr	Development of Novel Mouse Model of Ulcers Induced by Implantation of Magnets
title_full_unstemmed	Development of Novel Mouse Model of Ulcers Induced by Implantation of Magnets
title_sort	development of novel mouse model of ulcers induced by implantation of magnets
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d46508a340e443c3b1139c2ccfbaac9e
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_version_	1718388735325765632

Development of Novel Mouse Model of Ulcers Induced by Implantation of Magnets

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