Effect of Preconditioned Mesenchymal Stem Cells with Nisin Prebiotic on the Expression of Wound Healing Factors Such as TGF-β1, FGF-2, IL-1, IL-6, and IL-10

Stem cell therapy aims to replace damaged with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Mesenchymal stem cells (MSCs) have been applied for transplantation, but the disadvantage of MSC is that low survival rate following transplantation, so each strategy protects MSCs from cell death and increasing survival is valuable for therapy. Scaffold-based cell applications are a new approach to optimize cell delivery for wounds to enhance engraftment and paracrine activity of therapeutic stem cells. Nisin has now been shown to have antimicrobial activity against both gram-positive and gram-negative disease-associated pathogens. Preconditioning with protective factors is one strategy for protecting cells from harmful conditions and could be to enhance the survival and recovery of injured tissues. The aim of this article was to evaluate the effect of poly-L-lactic acid (PLLA) and preconditioning MSCs with Nisin in vitro cell survival. Mesenchymal stem cells were cultured and preconditioned with Nisin in different concentrations. After the evaluation of the sub-lethal dose of Nisin by MTT, in the next step, they were exposed to H2O2 or serum deprivation. Survival and anti-inflammation effects were evaluated by MTT assay and real-time PCR. Furthermore, the protein expression of TGF-beta 1 and FGF-2 was performed by ELISA. The 250 and 500 IU/mL of Nisin led to a significant anti-apoptotic impact on MSCs. Cell viability and proliferation in MSC-Nisin-PLLA significantly increased in comparison to the MSCs exposed in H2O2 or serum deprivation in 250-500 IU/mL Nisin. The gene expression of IL-10, TGF-beta, and FGF-2 was significantly up-regulated with Nisin treatment (p < 0.001, p < 0.01). Also, after cells treated with Nisin, TGF-beta and FGF-2 protein expression was increased (p < 0.01). In conclusion, Nisin could increase anti-inflammation factors. Lay Summary Mesenchymal stem cell (MSC) therapy has been very fascinated with wound healing. But the important limitation is that the MSCs are sensitive and short-lived in harsh conditions. Preconditioning is effective to increase cellular resistance and survival. Prebiotic Nisin is a good choice for MSC preconditioning. Nisin improves the stability of MSCs. Long-lived MSCs produce more anti-inflammatory and less inflammatory cytokines and growth factors, which help cell repair and differentiation into fibroblasts at the site of tissue damage. Besides, 3D porous scaffolds have been developed to support cell proliferation, allow oxygen exchange, and help the delivery of drugs and growth factors.