Generation of induced secretome from adipose-derived stem cells specialized for disease-specific treatment:An experimental mouse model

Bong Jun Kwak; Ha-Eun Hong; Haeyeon Seo; Ho Joong Choi; Joseph Ahn; Kee-Hwan Kim; Ok-Hee Kim; Sang Chul Lee; Say-June Kim

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Generation of induced secretome from adipose-derived stem cells specialized for disease-specific treatment:An experimental mouse model

Generation of induced secretome from adipose-derived stem cells specialized for disease-specific treatment:An experimental mouse model

作者：

Bong Jun Kwak Ha-Eun Hong Haeyeon Seo Ho Joong Choi Joseph Ahn Kee-Hwan Kim Ok-Hee Kim Sang Chul Lee Say-June Kim

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Adipose-derived

STEM

CELLS

Disease-specificity

Mesenchymal

STEM

CELLS

SECRETOME

Peroxiredoxin-1

THIOACETAMIDE

Toxic

hepatic

failure

摘要：

BACKGROUND Recently,the exclusive use of mesenchymal stem cell(MSC)-secreted molecules,named as the secretome,have been evaluated for overcoming the limitations of cell-based therapy while maintaining its advantages.AIM To improve cell-free therapy by adding disease-specificity through stimulation of MSCs using disease-causing materials.METHODS We collected the secretory materials(named as inducers)released from AML12 hepatocytes that had been pretreated with thioacetamide(TAA)and generated the TAA-induced secretome(TAA-isecretome)after stimulating adipose-derived stem cells with the inducers.The TAA-isecretome was intravenously administered to mice with TAA-induced hepatic failure and those with partial hepatectomy.RESULTS TAA-isecretome infusion showed higher therapeutic potential in terms of(1)restoring disorganized hepatic tissue to normal tissue;(2)inhibiting proinflammatory cytokines(interleukin-6 and tumor necrosis factor-α);and(3)reducing abnormally elevated liver enzymes(aspartate aminotransferase and alanine aminotransferase)compared to the na?ve secretome infusion in mice with TAA-induced hepatic failure.However,the TAA-isecretome showed inferior therapeutic potential for restoring hepatic function in partially hepatectomized mice.Proteomic analysis of TAA-isecretome identified that antioxidant processes were the most predominant enriched biological networks of the proteins exclusively identified in the TAA-isecretome.In addition,peroxiredoxin-1,a potent antioxidant protein,was found to be one of representative components of TAA-isecretome and played a central role in the protection of TAA-induced hepatic injury.CONCLUSION Appropriate stimulation of adipose-derived stem cells with TAA led to the production of a secretome enriched with proteins,especially peroxiredoxin-1,with higher antioxidant activity.Our results suggest that appropriate stimulation of MSCs with pathogenic agents can lead to the production of a secretome specialized for protecting against the pathogen.This approach is expected to ope

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篇名	Generation of induced secretome from adipose-derived stem cells specialized for disease-specific treatment:An experimental mouse model
来源期刊	世界干细胞杂志:英文版(电子版)	学科	医学
关键词	Adipose-derived STEM CELLS Disease-specificity Mesenchymal STEM CELLS SECRETOME Peroxiredoxin-1 THIOACETAMIDE Toxic hepatic failure
年，卷（期）	2020,（1）	所属期刊栏目
研究方向		页码范围	70-86
页数	17页	分类号	R73
字数		语种
DOI