TNF and periodontitis: Interestingly, Nakao Y et al. recently reported that priming GMSCs by TNF-α stimulation not only increased the exosome secretion but also the exosomal expression of CD73, thus enhancing their immunomodulatory effects on polarization of anti-inflammatory M2 macrophages in vitro (98). In vivo, local application of exosomes from TNF-α primed GMSCs display significantly enhanced therapeutic effects on a mice model of periodontitis as compared to treatment with naïve GMSC-derived exosomes (98).