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 beta 4 (T beta 4) is a novel trophic factor that has antimicrobial effects and the potential to promote tissue repair. T beta 4 is a ubiquitous, naturally-occurring peptide in the wound bed. Therefore, the relationship between T beta 4 and MSCs, especially adjacent adipose tissue-derived stem cells (ASCs), merits consideration. Exogenous T beta 4 treatment enhanced the proliferation of human ASCs, resulting in prominent nuclear localization of PCNA immunoreactivity. In addition, exogenous T beta 4 also increased IL-8 secretion and blocking of IL-8 with neutralizing antibodies decreased T beta 4-induced ASC proliferation, suggesting that IL-8 is a critical mediator of T beta 4-enhanced proliferation. Moreover, T beta 4 activated phosphorylation of ERK1/2 and increased the nuclear translocation of NF-kappa B. These observation provide that T beta 4 promotes the expansion of human ASCs via an IL-8-dependent mechanism that involves the ERK and NF-kappa B pathways. Therefore, T beta 4 could be used as a tool for MSC expansion in cell therapeutics. (C) 2013 Published by Elsevier Inc.