Abstract
uman mesenchymal stem cells (hMSCs) are multipotential progenitors that can differentiate into several types of cells. It also proved to retain low immunogenicity and an immunomodulatory effect. Since baculovirus mediates efficient gene transfer to mammalian cells, combine hMSCs with baculovirus would be a promising gene treatment. We had discovered baculovirus (BV) transduction of hMSCs triggered Toll-like receptor-3 (TLR3) pathway, including activation of downstream signal molecules (IRF3 and NF-κB) and cytokine( IL-6 and IL-8). Normal human cell reach senescence since telomere erosion with cell passage. To expand lifespan of hMSCs for large cells demand, it is necessarily to figure out the relationship between cell apoptosis and cell immunity. Here, we explore the immune responses against baculovirus of hMSCs with cell passage base on TLR3 signal pathway, and found that baculovirus-induced IL-6 and IL-8 increase while cells became old. Also TLR3 activation at P13 was more obvious than P9, resulting transcription factors, IRF3 and NF-κB, stronger translocation. On the other way, we immortalized hMSCs via hTERT transfection and made baculovirus transduction as usual, and discovered that cytokine secretion returned to the level of cell without transduction. These data demonstrate, for the first time, that the immune responses against baculovirus are severe at pre-senescence hMSCs. These findings underscore the importance of improving cell apoptosis for baculovirus gene vector application. We also evaluated the effects of baculovirus-induced miRNA at host cell immunity. Through siRNA inhibition at those miRNA, we found that secretion of IL-6 and IL-8 decreased since miR-143* inhibition. Above indicate that baculovirus-induced miRNA truly affect cell immunity.