Priming perspectives and MSCs robustness are currently under development. Pre-treating MSCs before injection may enhance the expression of fitness markers and stimulate greater therapeutic outcome. For instance, reports suggest cytokine mediated activation of MSCs lead to strong immunosuppressive behavior, and thereby attenuation of lung injury in rodents [31, 33], however some contradictory findings are also available as no effective role of proinflammatory cytokine priming was observed on MSCs in a model of acute lung injury and ARDS [34]. Therefore, the effect of cytokine priming needs to be further verified to prove the efficacy of primed MSCs in lung anomalies. Besides cytokines, priming of MSCs by growth factors is also a potent mechanism for MSC activation before infusion in pulmonary diseases [35]. Likewise, hypoxia preconditioning can also improve the proliferation and therapeutic efficacy of MSCs, as evident in bleomycin-induced pulmonary fibrosis model [36]. Further, employing pharmacological agents such as paclitaxel to prime MSCs could also be helpful in improving lung anomalies [37]. Therefore, in line with above findings it could reasonably by presume that MSC priming is a significant approach for treating pulmonary anomalies. In the light of above findings, herein, we propose that the mechanism of priming of MSC could be implied to the following: i) Licensing by pro-inflammatory cytokines such as IFN-γ, TNF-α, etc., to enhance immunosuppressive potential; ii) Priming by non-cytokines stimuli such as hormones/growth factors like HGF to boost defensive and protective cellular mechanisms; iii) Pre-conditioning by hypoxia, and/or pharmacological agents, e.g., sphingosine-1-phosphate, etc., to enhance engraftment and reparative effects; iv) Activation by spheroid culturing to enhance homing, survival, differentiation, and lineage specificity e.g. angiogenic mechanism; v) The timing of MSCs engraftment and engagement in the process of activation of immune cells to achieve the most excellent beneficial effect of MSCs infusion.