PPARβ/δ is involved in the cardioprotective effect of mesenchymal stem cells

C. Sarre, N. Nernpermpisooth, C. Barrere, P. Luz-Crawford, G. Tejedor, R. Contreras, A. Vincent, C. Jorgensen, J. Nargeot, F. Djouad, S. Barrere-Lemaire

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva


Introduction: Myocardial infarction ranks first for the mortality worldwide. Since adult hearts are unable to regenerate, fibrosis expands after infarction, leading to cardiac remodeling and heart failure. Adult mesenchymal stem cells (MSC) regenerative properties, as well as their safety and efficacy have been demonstrated in preclinical models but in clinical trials, their beneficial effects are controversial. MSC from mice knockout for the PPARbd nuclear receptor gene have been shown to provide a stronger therapeutic effect than MSC from wild-type mice in an experimental model of arthritis (Luz-Crawford et al., ARD 2016). Objective: The aim of our study was to compare the therapeutic effects of KO MSC cells and WT MSC versus the control condition (no MSC). Method: Hearts from C57Bl6 mice were subjected ex vivo to 30 minutes ischemia followed by 1-hour reperfusion. MSC from wild-type (WT MSC) and PPARbd knockout (KO MSC) mice were perfused on the Langendorff during reperfusion. The TTC-method was used to evaluate infarct size. Coronary effluents collected at t = 0 (before ischemia), t = 30 min and t = 60 min during reperfusion were analyzed for their cytokinic profile using CBA analysis. Results: The dose-response curve was established using various doses of MSC (3, 6 and 24.105 cells/heart): 6.105 was the optimal dose. Unexpectedly, the cardioprotective effect of WT MSC compared to control was lost using KO MSC. Our preliminary data have shown that KO MSC treatment decreases CXCL1 and IL-6 release versus control. By contrast, KO MSC injection increases IL-10 release versus control. All these effects were abolished when hearts were treated with KO MSC. Conclusion: Our study shows that both the cardioprotective and the anti-inflammatory effects of MSC are lost when PPARbd receptors are lacking. These results need to be confirmed: Mesoscale Discovery experiments are currently performed with those effluents.
Idioma originalInglés estadounidense
Páginas (desde-hasta)230
PublicaciónArchives of Cardiovascular Diseases Supplements
EstadoPublicada - oct. 2021


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