Systemic delivery of mesenchymal stem cells condition media in repeated doses acts as magic bullets in restoring IFN-γ/IL-4 balance in asthmatic rats

Aims: With respect to recent advantage in stem cell application, given the concern reported previously after stem cell transplantation, mesenchymal stem cell-derived conditioned media (MSC-CM) could be a potential approach to guarantee more safety and efficient outcomes than the current stem cell-based regenerative therapies. Main methods: Male rats were assigned into four experimental groups (n=6); healthy rats (C group), OVA sensitized rats (S group), OVA sensitized rats received a single dose of 50 mu l CM intravenously (S group + SD-CM) and OVA sensitized rats received repeated doses of 50 mu l CM intravenously (S group + RD-CM). Two weeks post-allergen challenge, the therapeutic effects of systemic administrated CM in single and repeated dosages were investigated by monitoring the transcription of T-bet, GATA-3, IL-4 and IFN-gamma genes along with pathological changes in asthmatic lung tissue. IL-4 and IFN-gamma levels and IFN-gamma/IL-4 ratio were further evaluated in sera. Key findings: Our data revealed that the systemic introduction of CM in repeated dosages could significantly reduce pathological injures in OVA-sensitized rats by the modulation of expression of T-bet and GATA-3 in lung tissues and interleukins levels (p < 0.001 to p < 0.05). In contrary, CM in single dosage did not yield any beneficial effect. Significance: Overall, we indicated that systemic administration of CM in repeated dosages, but not in single dose, could be strategic approach in amelioration of asthmatic changes, presumably by the regulating the differentiation of naive CD4 T cells into Th1/Th2 effector cells via modulation of T-bet and GATA-3 expression in OVA-sensitized male rats.