Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model

Abstract Notch signaling-modified human mesenchymal stem cell, SB623 cell, is a promising cell therapy product for ischemic stroke. With the aim to expand indications for their use for critical limb-threatening ischemia (CLTI), we hypothesized that SB623 cells improved tissue perfusion by inducing a...

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Autores principales:	Shusaku Maeda, Shigeru Miyagawa, Takuji Kawamura, Takashi Shibuya, Kenichi Watanabe, Takaya Nakagawa, Akima Harada, Dai Chida, Yoshiki Sawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d4292c66fd8248e985ea76f5ffbfea56
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spelling	oai:doaj.org-article:d4292c66fd8248e985ea76f5ffbfea562021-12-02T13:24:36ZNotch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model10.1038/s41598-021-82284-32045-2322https://doaj.org/article/d4292c66fd8248e985ea76f5ffbfea562021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82284-3https://doaj.org/toc/2045-2322Abstract Notch signaling-modified human mesenchymal stem cell, SB623 cell, is a promising cell therapy product for ischemic stroke. With the aim to expand indications for their use for critical limb-threatening ischemia (CLTI), we hypothesized that SB623 cells improved tissue perfusion by inducing angiogenesis or arteriogenesis in a hindlimb ischemia model rat. In Sprague–Dawley rats, hindlimb ischemia was generated by femoral artery removal, then seven days after ischemic induction 1 × 105 SB623 cells or PBS was injected into the ischemic adductor muscle. As compared with the PBS group, tissue perfusion was significantly increased in the SB623 group. While capillary density did not vary between the groups, αSMA- and vWF-positive arterioles with a diameter > 15 μm were significantly increased in the SB623 group. Whole transcriptome analysis of endothelial cells co-cultured with SB623 cells showed upregulation of the Notch signaling pathway as well as several other pathways potentially leading to arteriogenesis. Furthermore, rat muscle treated with SB623 cells showed a trend for higher ephrin-B2 and significantly higher EphB4 expression, which are known as arteriogenic markers. In the hindlimb ischemia model, SB623 cells improved tissue perfusion by inducing arteriogenesis, suggesting a promising cell source for treatment of CLTI.Shusaku MaedaShigeru MiyagawaTakuji KawamuraTakashi ShibuyaKenichi WatanabeTakaya NakagawaAkima HaradaDai ChidaYoshiki SawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shusaku Maeda Shigeru Miyagawa Takuji Kawamura Takashi Shibuya Kenichi Watanabe Takaya Nakagawa Akima Harada Dai Chida Yoshiki Sawa Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model
description	Abstract Notch signaling-modified human mesenchymal stem cell, SB623 cell, is a promising cell therapy product for ischemic stroke. With the aim to expand indications for their use for critical limb-threatening ischemia (CLTI), we hypothesized that SB623 cells improved tissue perfusion by inducing angiogenesis or arteriogenesis in a hindlimb ischemia model rat. In Sprague–Dawley rats, hindlimb ischemia was generated by femoral artery removal, then seven days after ischemic induction 1 × 105 SB623 cells or PBS was injected into the ischemic adductor muscle. As compared with the PBS group, tissue perfusion was significantly increased in the SB623 group. While capillary density did not vary between the groups, αSMA- and vWF-positive arterioles with a diameter > 15 μm were significantly increased in the SB623 group. Whole transcriptome analysis of endothelial cells co-cultured with SB623 cells showed upregulation of the Notch signaling pathway as well as several other pathways potentially leading to arteriogenesis. Furthermore, rat muscle treated with SB623 cells showed a trend for higher ephrin-B2 and significantly higher EphB4 expression, which are known as arteriogenic markers. In the hindlimb ischemia model, SB623 cells improved tissue perfusion by inducing arteriogenesis, suggesting a promising cell source for treatment of CLTI.
format	article
author	Shusaku Maeda Shigeru Miyagawa Takuji Kawamura Takashi Shibuya Kenichi Watanabe Takaya Nakagawa Akima Harada Dai Chida Yoshiki Sawa
author_facet	Shusaku Maeda Shigeru Miyagawa Takuji Kawamura Takashi Shibuya Kenichi Watanabe Takaya Nakagawa Akima Harada Dai Chida Yoshiki Sawa
author_sort	Shusaku Maeda
title	Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model
title_short	Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model
title_full	Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model
title_fullStr	Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model
title_full_unstemmed	Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model
title_sort	notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d4292c66fd8248e985ea76f5ffbfea56
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Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model

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