title: Apple ethanol extract promotes proliferation of human adult stem cells, which involves the regenerative potential of stem cells.
abstract: Tissue regeneration using adult stem cells (ASCs) has significant potential as a novel treatment for many degenerative diseases. Previous studies have established that age negatively affects the proliferation status and differentiation potential of ASCs, suggesting a possible limitation in their potential therapeutic use. Therefore, we hypothesized that apple extract might exert beneficial effects on ASCs. The specific objectives were to investigate the proliferative effect of apple ethanol extract on human adipose tissue-derived mesenchymal stem cells (ADSCs) and human cord blood-derived mesenchymal stem cells (CB-MSCs), and identify the possible molecular mechanisms. Apple extract promoted proliferation of ADSCs and CB-MSCs as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Click-iT 5-ethynyl-2'-deoxyuridine flow cytometry assays. In addition, phosphorylation of p44/42 MAPK (ERK), mammalian target of rapamycin (mTOR), p70 S6 kinase (p70S6K), S6 ribosomal protein (S6RP), eukaryotic initiation factor (eIF) 4B and eIF4E was induced stepwise in ADSCs. Furthermore, apple extract significantly induced the production of vascular endothelial growth factor and interleukin-6 in both ADSCs and CB-MSCs. Similarly, apple extract-induced phosphorylation of the mTOR/p70S6K/S6RP/eIF4B/eIF4E pathway was blocked by pretreatment with PD98059, a specific ERK inhibitor. These results indicate that apple extract-induced proliferation of ADSCs under serum-free conditions is mediated by ERK-dependent cytokine production. Moreover, the beneficial effect of apple extract on proliferation of ASCs may overcome the limitation in therapeutic use of stem cells in tissue regeneration and maintenance of stem cell homeostasis.
authors.affiliation: Viral Disease Division, Animal and Plant Quarantine Agency, 177 Hyeoksin-Ro, Gimcheon City, 396-60, Gyeongsangbuk Do, Republic of Korea.
authors.forename: Jienny
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Beauty and Cosmetic Science, College of Health Science, Eulji University, Seongnam City, 131-35, Gyunggi Do, Republic of Korea.
authors.forename: Moon Sam
authors.initials: MS
authors.lastname: Shin
authors.affiliation: Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City, 164-19, Gyunggi Do, Republic of Korea.
authors.forename: Mi Ok
authors.initials: MO
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City, 164-19, Gyunggi Do, Republic of Korea.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Jang
authors.affiliation: Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City, 164-19, Gyunggi Do, Republic of Korea.
authors.forename: Sae Woong
authors.initials: SW
authors.lastname: Oh
authors.affiliation: Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City, 164-19, Gyunggi Do, Republic of Korea.
authors.forename: Mingyeong
authors.initials: M
authors.lastname: Kang
authors.affiliation: Skincure Life Science Institute, Seongnam City, 132-16, Gyunggi Do, Republic of Korea.
authors.forename: Kwangseon
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Microbiology, School of Medicine, Kyung Hee University, 024-53 Seoul, Republic of Korea. Electronic address: yongseek@khu.ac.kr.
authors.forename: Yong Seek
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City, 164-19, Gyunggi Do, Republic of Korea. Electronic address: bioneer@skku.edu.
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
mesh_terms: D000273:Adipose Tissue; D000328:Adult; D053687:Adult Stem Cells / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects*; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D005312:Fetal Blood; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D027845:Malus; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D012038:Regeneration; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D039642:Eukaryotic Initiation Factors; C508600:IL6 protein, human; D015850:Interleukin-6; D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; C031799:eIF-4B; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D048052:Mitogen-Activated Protein Kinase 3; C022616:thiazolyl blue; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine
keywords: Adult stem cells; Apple extract; Cytokines; ERK; mTOR pathway