Combined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart

Abstract Although endogenous cardiac repair by recruitment of stem cells may serve as a therapeutic approach to healing a damaged heart, how to effectively enhance the migration of stem cells to the damaged heart is unclear. Here, we examined whether the combined administration of prostacyclin agoni...

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Autores principales:	Nagako Sougawa, Shigeru Miyagawa, Takuji Kawamura, Ryohei Matsuura, Akima Harada, Yoshiki Sakai, Noriko Mochizuki-Oda, Ryoko Sato-Nishiuchi, Kiyotoshi Sekiguchi, Yoshiki Sawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d5eab8b2b872415c8dba102b5032a1ae
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spelling	oai:doaj.org-article:d5eab8b2b872415c8dba102b5032a1ae2021-11-21T12:24:17ZCombined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart10.1038/s41598-021-00918-y2045-2322https://doaj.org/article/d5eab8b2b872415c8dba102b5032a1ae2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00918-yhttps://doaj.org/toc/2045-2322Abstract Although endogenous cardiac repair by recruitment of stem cells may serve as a therapeutic approach to healing a damaged heart, how to effectively enhance the migration of stem cells to the damaged heart is unclear. Here, we examined whether the combined administration of prostacyclin agonist (ONO1301), a multiple-cytokine inducer, and stem cell niche laminin-221 (LM221), enhances regeneration through endogenous cardiac repair. We administered ONO1301- and LM221-immersed sheets, LM221-immersed sheets, ONO1301-immersed sheets, and PBS-immersed sheets (control) to an acute infarction rat model. Four weeks later, cardiac function, histology, and cytokine expression were analysed. The combined administration of LM221 and ONO1301 upregulated angiogenic and chemotactic factors in the myocardium after 4 weeks and enhanced the accumulation of ILB4 positive cells, SMA positive cells, and platelet-derived growth factor receptor alpha (PDGFRα) and CD90 double-positive cells, leading to the generation of mature microvascular networks. Interstitial fibrosis reduced and functional recovery was prominent in LM221- and ONO1301-administrated hearts as compared with those in ONO1301-administrated or control hearts. LM221 and ONO1301 combination enhanced recruitment of PDGFRα and CD90 double-positive cells, maturation of vessels, and functional recovery in rat acute myocardial infarction hearts, highlighting a new promising acellular approach for the failed heart.Nagako SougawaShigeru MiyagawaTakuji KawamuraRyohei MatsuuraAkima HaradaYoshiki SakaiNoriko Mochizuki-OdaRyoko Sato-NishiuchiKiyotoshi SekiguchiYoshiki SawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nagako Sougawa Shigeru Miyagawa Takuji Kawamura Ryohei Matsuura Akima Harada Yoshiki Sakai Noriko Mochizuki-Oda Ryoko Sato-Nishiuchi Kiyotoshi Sekiguchi Yoshiki Sawa Combined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart
description	Abstract Although endogenous cardiac repair by recruitment of stem cells may serve as a therapeutic approach to healing a damaged heart, how to effectively enhance the migration of stem cells to the damaged heart is unclear. Here, we examined whether the combined administration of prostacyclin agonist (ONO1301), a multiple-cytokine inducer, and stem cell niche laminin-221 (LM221), enhances regeneration through endogenous cardiac repair. We administered ONO1301- and LM221-immersed sheets, LM221-immersed sheets, ONO1301-immersed sheets, and PBS-immersed sheets (control) to an acute infarction rat model. Four weeks later, cardiac function, histology, and cytokine expression were analysed. The combined administration of LM221 and ONO1301 upregulated angiogenic and chemotactic factors in the myocardium after 4 weeks and enhanced the accumulation of ILB4 positive cells, SMA positive cells, and platelet-derived growth factor receptor alpha (PDGFRα) and CD90 double-positive cells, leading to the generation of mature microvascular networks. Interstitial fibrosis reduced and functional recovery was prominent in LM221- and ONO1301-administrated hearts as compared with those in ONO1301-administrated or control hearts. LM221 and ONO1301 combination enhanced recruitment of PDGFRα and CD90 double-positive cells, maturation of vessels, and functional recovery in rat acute myocardial infarction hearts, highlighting a new promising acellular approach for the failed heart.
format	article
author	Nagako Sougawa Shigeru Miyagawa Takuji Kawamura Ryohei Matsuura Akima Harada Yoshiki Sakai Noriko Mochizuki-Oda Ryoko Sato-Nishiuchi Kiyotoshi Sekiguchi Yoshiki Sawa
author_facet	Nagako Sougawa Shigeru Miyagawa Takuji Kawamura Ryohei Matsuura Akima Harada Yoshiki Sakai Noriko Mochizuki-Oda Ryoko Sato-Nishiuchi Kiyotoshi Sekiguchi Yoshiki Sawa
author_sort	Nagako Sougawa
title	Combined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart
title_short	Combined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart
title_full	Combined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart
title_fullStr	Combined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart
title_full_unstemmed	Combined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart
title_sort	combined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d5eab8b2b872415c8dba102b5032a1ae
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Combined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart

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