Thymosin beta-4 promotes mesenchymal stem cell proliferation via an interleukin-8-dependent mechanism.

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 ß4 (Tß4) is a novel trophic factor that has antimicrobial effects and the potential to promote tissue repair. Tß4 is a ubiquitous, naturally-occurring peptide in the wound bed. Therefore, the relationship between Tß4 and MSCs, especially adjacent adipose tissue-derived stem cells (ASCs), merits consideration. Exogenous Tß4 treatment enhanced the proliferation of human ASCs, resulting in prominent nuclear localization of PCNA immunoreactivity. In addition, exogenous Tß4 also increased IL-8 secretion and blocking of IL-8 with neutralizing antibodies decreased Tß4-induced ASC proliferation, suggesting that IL-8 is a critical mediator of Tß4-enhanced proliferation. Moreover, Tß4 activated phosphorylation of ERK1/2 and increased the nuclear translocation of NF-κB. These observation provide that Tß4 promotes the expansion of human ASCs via an IL-8-dependent mechanism that involves the ERK and NF-κB pathways. Therefore, Tß4 could be used as a tool for MSC expansion in cell therapeutics.