MMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds

Introduction: Intractable ulcers may ultimately lead to amputation. To promote wound healing, researchers developed a serum-free ex vivo peripheral blood mononuclear cell quality and quantity culture (MNC-QQc) as a source for cell therapy. In mice, pigs, and even humans, cell therapy with MNC-QQc re...

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Autores principales:	Tsubame Nishikai-Yan Shen, Makiko Kado, Hiroko Hagiwara, Satoshi Fujimura, Hiroshi Mizuno, Rica Tanaka
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	MMP9 Wound healing Cell therapy Cell culture MNC-QQc Medicine (General) R5-920 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/e1df63111d76455a9d7f488f5bde7514
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spelling	oai:doaj.org-article:e1df63111d76455a9d7f488f5bde75142021-11-06T04:30:19ZMMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds2352-320410.1016/j.reth.2021.10.003https://doaj.org/article/e1df63111d76455a9d7f488f5bde75142021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S235232042100081Xhttps://doaj.org/toc/2352-3204Introduction: Intractable ulcers may ultimately lead to amputation. To promote wound healing, researchers developed a serum-free ex vivo peripheral blood mononuclear cell quality and quantity culture (MNC-QQc) as a source for cell therapy. In mice, pigs, and even humans, cell therapy with MNC-QQc reportedly yields a high regenerative efficacy. However, the mechanism of wound healing by MNC-QQc cells remains largely unknown. Hence, using an in vitro wound healing model, this study aimed to investigate MNC-QQc cells and the migratory potential of dermal fibroblasts. Methods: After separation from a 50 mL blood sample from healthy individuals, mononuclear cells were cultured for 7 days in a serum-free ex vivo expansion system with five different cytokines (MNC-QQc method). The effects of MNC-QQc cells on human dermal fibroblast migration were observed by scratch assay. An angiogenesis array screened the MNC-QQc cell supernatant for proteins related to wound healing. Finally, fibroblast migration was confirmed by observing the intracellular signal transduction pathways via Western blot. Results: The migration of fibroblasts co-cultured with MNC-QQc cells increased by matrix metallopeptidase-9 (MMP9) secretion, as suggested by the angiogenesis array. Furthermore, the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in fibroblast/MNC-QQc cell co-culture and fibroblast culture with added recombinant human MMP9 protein increased. When fibroblasts were cultured with either an MMP9 inhibitor or a STAT3 inhibitor, both fibroblast migration and STAT3 phosphorylation were significantly suppressed. Conclusions: MNC-QQc cells promote wound healing by the secretion of MMP9, which induces fibroblast migration via the STAT3 signaling pathway.Tsubame Nishikai-Yan ShenMakiko KadoHiroko HagiwaraSatoshi FujimuraHiroshi MizunoRica TanakaElsevierarticleMMP9Wound healingCell therapyCell cultureMNC-QQcMedicine (General)R5-920CytologyQH573-671ENRegenerative Therapy, Vol 18, Iss , Pp 464-471 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MMP9 Wound healing Cell therapy Cell culture MNC-QQc Medicine (General) R5-920 Cytology QH573-671
spellingShingle	MMP9 Wound healing Cell therapy Cell culture MNC-QQc Medicine (General) R5-920 Cytology QH573-671 Tsubame Nishikai-Yan Shen Makiko Kado Hiroko Hagiwara Satoshi Fujimura Hiroshi Mizuno Rica Tanaka MMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds
description	Introduction: Intractable ulcers may ultimately lead to amputation. To promote wound healing, researchers developed a serum-free ex vivo peripheral blood mononuclear cell quality and quantity culture (MNC-QQc) as a source for cell therapy. In mice, pigs, and even humans, cell therapy with MNC-QQc reportedly yields a high regenerative efficacy. However, the mechanism of wound healing by MNC-QQc cells remains largely unknown. Hence, using an in vitro wound healing model, this study aimed to investigate MNC-QQc cells and the migratory potential of dermal fibroblasts. Methods: After separation from a 50 mL blood sample from healthy individuals, mononuclear cells were cultured for 7 days in a serum-free ex vivo expansion system with five different cytokines (MNC-QQc method). The effects of MNC-QQc cells on human dermal fibroblast migration were observed by scratch assay. An angiogenesis array screened the MNC-QQc cell supernatant for proteins related to wound healing. Finally, fibroblast migration was confirmed by observing the intracellular signal transduction pathways via Western blot. Results: The migration of fibroblasts co-cultured with MNC-QQc cells increased by matrix metallopeptidase-9 (MMP9) secretion, as suggested by the angiogenesis array. Furthermore, the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in fibroblast/MNC-QQc cell co-culture and fibroblast culture with added recombinant human MMP9 protein increased. When fibroblasts were cultured with either an MMP9 inhibitor or a STAT3 inhibitor, both fibroblast migration and STAT3 phosphorylation were significantly suppressed. Conclusions: MNC-QQc cells promote wound healing by the secretion of MMP9, which induces fibroblast migration via the STAT3 signaling pathway.
format	article
author	Tsubame Nishikai-Yan Shen Makiko Kado Hiroko Hagiwara Satoshi Fujimura Hiroshi Mizuno Rica Tanaka
author_facet	Tsubame Nishikai-Yan Shen Makiko Kado Hiroko Hagiwara Satoshi Fujimura Hiroshi Mizuno Rica Tanaka
author_sort	Tsubame Nishikai-Yan Shen
title	MMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds
title_short	MMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds
title_full	MMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds
title_fullStr	MMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds
title_full_unstemmed	MMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds
title_sort	mmp9 secreted from mononuclear cell quality and quantity culture mediates stat3 phosphorylation and fibroblast migration in wounds
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/e1df63111d76455a9d7f488f5bde7514
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_version_	1718443888258056192

MMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds

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