FGF2-primed 3D spheroids producing IL-8 promote therapeutic angiogenesis in murine hindlimb ischemia

Abstract Peripheral artery disease is a progressive, devastating disease that leads to critical limb ischemia (CLI). Therapeutic angiogenesis using stem cell therapy has emerged as a promising approach for its treatment; however, adapting cell-based therapy has been limited by poor cell survival and...

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Autores principales:	Jungkyun Choi, Wooshik Choi, Yunji Joo, Haeun Chung, Dokyun Kim, Seung Ja Oh, Sang-Heon Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/9f82ccb5f8b1426583a1c44e3d70a113
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spelling	oai:doaj.org-article:9f82ccb5f8b1426583a1c44e3d70a1132021-12-02T15:10:56ZFGF2-primed 3D spheroids producing IL-8 promote therapeutic angiogenesis in murine hindlimb ischemia10.1038/s41536-021-00159-72057-3995https://doaj.org/article/9f82ccb5f8b1426583a1c44e3d70a1132021-08-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00159-7https://doaj.org/toc/2057-3995Abstract Peripheral artery disease is a progressive, devastating disease that leads to critical limb ischemia (CLI). Therapeutic angiogenesis using stem cell therapy has emerged as a promising approach for its treatment; however, adapting cell-based therapy has been limited by poor cell survival and low treatment efficiency. To overcome unmet clinical needs, we developed a fibroblast growth factor 2 (FGF2)-immobilized matrix that enabled control of cell adhesion to the surface and exerted a priming effect on the cell. Human adipose-derived stem cells (hASCs) grown in this matrix formed a functionally enhanced cells spheroid (FECS-Ad) that secreted various angiogenic factors including interleukin-8 (IL-8). We demonstrated that IL-8 was upregulated by the FGF2-mediated priming effect during FECS-Ad formation. Immobilized FGF2 substrate induced stronger IL-8 expression than soluble FGF2 ligands, presumably through the FGFR1/JNK/NF-κB signaling cascade. In IL-8-silenced FECS-Ad, vascular endothelial growth factor (VEGF) expression was decreased and angiogenic potential was reduced. Intramuscular injection of FECS-Ad promoted angiogenesis and muscle regeneration in mouse ischemic tissue, while IL-8 silencing in FECS-Ad inhibited these effects. Taken together, our data demonstrate that IL-8 contributes to therapeutic angiogenesis and suggest that FECS-Ad generated using the MBP-FGF2 matrix might provide a reliable platform for developing therapeutic agents to treat CLI.Jungkyun ChoiWooshik ChoiYunji JooHaeun ChungDokyun KimSeung Ja OhSang-Heon KimNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Jungkyun Choi Wooshik Choi Yunji Joo Haeun Chung Dokyun Kim Seung Ja Oh Sang-Heon Kim FGF2-primed 3D spheroids producing IL-8 promote therapeutic angiogenesis in murine hindlimb ischemia
description	Abstract Peripheral artery disease is a progressive, devastating disease that leads to critical limb ischemia (CLI). Therapeutic angiogenesis using stem cell therapy has emerged as a promising approach for its treatment; however, adapting cell-based therapy has been limited by poor cell survival and low treatment efficiency. To overcome unmet clinical needs, we developed a fibroblast growth factor 2 (FGF2)-immobilized matrix that enabled control of cell adhesion to the surface and exerted a priming effect on the cell. Human adipose-derived stem cells (hASCs) grown in this matrix formed a functionally enhanced cells spheroid (FECS-Ad) that secreted various angiogenic factors including interleukin-8 (IL-8). We demonstrated that IL-8 was upregulated by the FGF2-mediated priming effect during FECS-Ad formation. Immobilized FGF2 substrate induced stronger IL-8 expression than soluble FGF2 ligands, presumably through the FGFR1/JNK/NF-κB signaling cascade. In IL-8-silenced FECS-Ad, vascular endothelial growth factor (VEGF) expression was decreased and angiogenic potential was reduced. Intramuscular injection of FECS-Ad promoted angiogenesis and muscle regeneration in mouse ischemic tissue, while IL-8 silencing in FECS-Ad inhibited these effects. Taken together, our data demonstrate that IL-8 contributes to therapeutic angiogenesis and suggest that FECS-Ad generated using the MBP-FGF2 matrix might provide a reliable platform for developing therapeutic agents to treat CLI.
format	article
author	Jungkyun Choi Wooshik Choi Yunji Joo Haeun Chung Dokyun Kim Seung Ja Oh Sang-Heon Kim
author_facet	Jungkyun Choi Wooshik Choi Yunji Joo Haeun Chung Dokyun Kim Seung Ja Oh Sang-Heon Kim
author_sort	Jungkyun Choi
title	FGF2-primed 3D spheroids producing IL-8 promote therapeutic angiogenesis in murine hindlimb ischemia
title_short	FGF2-primed 3D spheroids producing IL-8 promote therapeutic angiogenesis in murine hindlimb ischemia
title_full	FGF2-primed 3D spheroids producing IL-8 promote therapeutic angiogenesis in murine hindlimb ischemia
title_fullStr	FGF2-primed 3D spheroids producing IL-8 promote therapeutic angiogenesis in murine hindlimb ischemia
title_full_unstemmed	FGF2-primed 3D spheroids producing IL-8 promote therapeutic angiogenesis in murine hindlimb ischemia
title_sort	fgf2-primed 3d spheroids producing il-8 promote therapeutic angiogenesis in murine hindlimb ischemia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9f82ccb5f8b1426583a1c44e3d70a113
work_keys_str_mv	AT jungkyunchoi fgf2primed3dspheroidsproducingil8promotetherapeuticangiogenesisinmurinehindlimbischemia AT wooshikchoi fgf2primed3dspheroidsproducingil8promotetherapeuticangiogenesisinmurinehindlimbischemia AT yunjijoo fgf2primed3dspheroidsproducingil8promotetherapeuticangiogenesisinmurinehindlimbischemia AT haeunchung fgf2primed3dspheroidsproducingil8promotetherapeuticangiogenesisinmurinehindlimbischemia AT dokyunkim fgf2primed3dspheroidsproducingil8promotetherapeuticangiogenesisinmurinehindlimbischemia AT seungjaoh fgf2primed3dspheroidsproducingil8promotetherapeuticangiogenesisinmurinehindlimbischemia AT sangheonkim fgf2primed3dspheroidsproducingil8promotetherapeuticangiogenesisinmurinehindlimbischemia
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FGF2-primed 3D spheroids producing IL-8 promote therapeutic angiogenesis in murine hindlimb ischemia

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