The human amniotic fluid stem cell secretome effectively counteracts doxorubicin-induced cardiotoxicity

• DOI: 10.1038/srep29994
• Publication Date: 2016-07-22T05:32:36Z
• Authors: Edoardo Lazzarini; Carolina Balbi; Paola Altieri; Ulrich Pfeffer; Elisa Gambini; Marco Canepa; Luigi Varesio; Maria Carla Bosco; Domenico Coviello; Giulio Pompilio; Claudio Brunelli; Ranieri Cancedda; Pietro Ameri; Sveva Bollini
• Keywords: Cardiotoxicity; CXCL1

Abstract The anthracycline doxorubicin (Dox) is widely used in oncology, but it may cause a cardiomyopathy with bleak prognosis that cannot be effectively prevented. secretome of human amniotic fluid-derived stem cells (hAFS) has previously been demonstrated to significantly reduce ischemic cardiac damage. Here shown that, following hypoxic preconditioning, hAFS conditioned medium (hAFS-CM) antagonizes senescence and apoptosis cardiomyocytes progenitor cells, two major features Dox cardiotoxicity. Mechanistic studies mouse neonatal ventricular (mNVCM) reveal hAFS-CM inhibition Dox-elicited associated decreased DNA damage, nuclear translocation NF-kB upregulation the controlled genes, Il6 Cxcl1 , promoting mNVCM survival. Furthermore, induces expression efflux transporter, Abcb1b extrusion from mNVCM. PI3K/Akt signaling cascade, upstream NF-kB, potently activated by pre-treatment PI3K inhibitor abrogates accumulation into nucleus, modulation prevention Dox-initiated response hAFS-CM. These results support concept are valuable source cardioprotective factors lay foundations for development cell-based paracrine treatment chemotherapy-related