title: Thymosin beta-4 promotes mesenchymal stem cell proliferation via an interleukin-8-dependent mechanism.
abstract: Mesenchymal stem cells (MSCs) hold great promise for the field of tissue regeneration. Because only a limited number of MSCs can be obtained from each donor site, it is important to establish standard methods for MSC expansion using growth and trophic factors. Thymosin β4 (Tβ4) is a novel trophic factor that has antimicrobial effects and the potential to promote tissue repair. Tβ4 is a ubiquitous, naturally-occurring peptide in the wound bed. Therefore, the relationship between Tβ4 and MSCs, especially adjacent adipose tissue-derived stem cells (ASCs), merits consideration. Exogenous Tβ4 treatment enhanced the proliferation of human ASCs, resulting in prominent nuclear localization of PCNA immunoreactivity. In addition, exogenous Tβ4 also increased IL-8 secretion and blocking of IL-8 with neutralizing antibodies decreased Tβ4-induced ASC proliferation, suggesting that IL-8 is a critical mediator of Tβ4-enhanced proliferation. Moreover, Tβ4 activated phosphorylation of ERK1/2 and increased the nuclear translocation of NF-κB. These observation provide that Tβ4 promotes the expansion of human ASCs via an IL-8-dependent mechanism that involves the ERK and NF-κB pathways. Therefore, Tβ4 could be used as a tool for MSC expansion in cell therapeutics.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Korea University Medical Center, Gojan 1-dong, Danwon-gu, Ansan-si, Gyeonggi-do 425-707, Republic of Korea.
authors.forename: Byung-Joon
authors.initials: BJ
authors.lastname: Jeon
authors.forename: Yoolhee
authors.initials: Y
authors.lastname: Yang
authors.forename: Su
authors.initials: S
authors.lastname: Kyung Shim
authors.forename: Heung-Mo
authors.initials: HM
authors.lastname: Yang
authors.forename: Daeho
authors.initials: D
authors.lastname: Cho
authors.forename: Sa
authors.initials: S
authors.lastname: Ik Bang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000273:Adipose Tissue / Q000166:cytology; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D013947:Thymosin / Q000494:pharmacology*; D000099201:Thymosin beta(4)
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D016209:Interleukin-8; D018809:Proliferating Cell Nuclear Antigen; D013947:Thymosin; D000099201:Thymosin beta(4); C508606:CXCL8 protein, human
keywords: Cell proliferation; ERK pathway, NF-κB; Interleukin-8; Mesenchymal stem cells; Thymosin β4