br Materials and Methods br

Materials and Methods
Results
Discussion The prophylactic tolerance protocol entails the administration of immunosuppressive drugs. Rapamycin is an mTOR inhibitor approved for immunosuppression in organ transplantation (and is commonly used in children (Ganschow et al., 2013)) and has potent tolerogenic properties (Fischer et al., 2009; Battaglia et al., 2005). CTLA4Ig (abatacept) and its derivative belatacept are approved for use in rheumatoid arthritis and organ transplantation, respectively (Bonelli et al., 2013; Wekerle and Grinyo, 2012), and have tolerogenic effects as well. However, neither mTOR inhibition, nor CTLA4Ig are effective in establishing robust tolerance on their own, (Linhart et al., 2007; Pilat et al., 2011). The toxicity of these immunosuppressive drugs is expected to be low when given for a short-course treatment in the period of allergic sensitization (Westman et al., 2015). Specifically, the combination of rapamycin and belatacept has been tested in renal transplantation and was found to be safe (Ferguson et al., 2011). No anti-CD40L mAb is clinically available yet, but next generation anti-CD40L domain antibodies avoiding the thromboembolic side effects observed with conventional anti-CD40L mAbs are under pre-clinical development (Suchard et al., 2013; Xie et al., 2014), and anti-CD40 mAbs could soon offer an alternative as well (Goldwater et al., 2013). The presented cell therapy regimen does not require any cytotoxic or myelosuppressive preconditioning which has been necessary for BM engraftment in various previous BMT regimens (Baranyi et al., 2008; Baranyi et al., 2012), further limiting potential safety risks. While cells from a transgenic mouse were used in the present experiments, expression of Anti-infection Compound Library on the surface of autologous cells might be feasible through various means. Retroviral transduction is currently insufficiently safe for non-vital indications (Hacein-Bey-Abina et al., 2010), but site-specific integration of genes into HSC of cord blood became recently possible and might eventually provide a viable option (Genovese et al., 2014). Chemical coupling of allergens might provide an attractive alternative (Jenkins and Schwartz, 2009; Getts et al., 2011). While not directly tested in the present study, antigen expression is likely required for a limited period only, as transient chimerism is effective in permanently tolerizing an alloresponse in experimental models (Tian et al., 2002; Tian et al., 2006) and the clinical setting (Kawai et al., 2008). The use of hypoallergenic allergen derivatives (Valenta et al., 2010), or allergen-derived peptides containing the relevant T cell epitopes (Focke-Tejkl et al., 2014), might further enhance the safety aspects of this approach, avoiding the risk of triggering anaphylaxis. Mobilized peripheral blood stem cells have been successfully used instead of BM cells in the setting of transplantation tolerance (Koporc et al., 2008; Scandling et al., 2008), and would be a clinically more acceptable cell source as they can be obtained non-invasively. Eventually, cord-blood could serve as the ideal hematopoietic cells source (Pineault and Abu-Khader, 2015).
Authors\' Contributions
Disclosure
Introduction Cardiovascular disease remains the most common cause of mortality worldwide, accounting for more than 17 million deaths annually (Anon., 2011). Myocardial infarction (MI) leads to irreversible myocardial sequelae, often causing debilitating symptoms and shortening life span. Recently, biological regenerative innovations have been introduced as promising therapeutic options (Soler-Botija et al., 2012; Gálvez-Montón et al., 2013a; Prat-Vidal et al., 2014). Cardiac fat contains a population of mesenchymal-like progenitor cells capable of differentiating into cells that closely resemble cardiomyocytes, both morphologically and molecularly. In murine MI models, these cells improved cardiac function parameters and promoted local neoangiogenesis under hypoxia (Bayes-Genis et al., 2010). The adipose tissue surrounding the heart and pericardium may serve as an autologous biological matrix for salvaging injured myocardium.