Introduction: Anthracyclines are highly effective chemotherapeutic agents associated with cardiac toxicity. Anthracycline induced cardiomyopathy (AIC) carries a reported mortality rate in excess of 20% at four years on medical therapy. Effective therapies for AIC have not been established. The Stem Cell Injection for Cancer Survivors (SeNeCA) trial is examining the role of allogenic mesenchymal stem cell (MSC) therapy in treating AIC. To understand the mechanism and predict the efficacy of MSCs in myocardial recovery, we evaluated the restorative effects of MSCs following doxorubicin (dox) administration in vitro , employing iPSC- derived cardiomyocytes (iCM) generated from trial patients. Hypothesis: MSCs will rescue AIC patient-specific iCM from dox injury. Methods and Results: We generated three AIC patient-specific iPSC lines from SeNeCA patients. In vitro dox sensitivity was shown to be comparable to published values for AIC patient iCM. iCM were then cultured in 1μM dox for 24hrs and assessed for viability and apoptosis 72- hours post-injury by annexin-PI, ApoLive Glo, and tetrazolium (MTT) assay. MSC efficacy was assessed using co-culture. 2.5 x 10^5 iCM were plated and co-cultured with 2.5 x 10^5 MSC using a 1μm pore trans-well system. Compared to monoculture, MSC co-culture improved post- doxorubicin iCM viability significantly (50.0±4.0%* vs 35.7±0.8%, *p-value< 0.005) by MTT and reduced apoptosis significantly (40.4±2.9%* vs 48.6±0.8%, *p-value<0.01). Reactive oxygen species (ROS) production was also reduced (25.5%* vs 16%) by CellRox. MSC-derived microvesicles (MV) were assessed as potential effector molecules. MV demonstrated a dose- dependent effect with statistically significant improvement in viability achieved at a dose of ~500 MV/cell (44.5±4.4%* vs. 34.9±4.4%, *p-value<0.06) by MTT. Results were corroborated by ApoLive Glo and annexin PI showing significantly reduced apoptosis and increased viability. Conclusion: Allogeneic MSCs can attenuate apoptosis and ROS production following doxorubicin injury in patient-specific iCM. This effect is largely mediated via MV. Our findings will be validated by the SeNeCA trial demonstrating proof-of-concept in in vitro clinical trials employing iPSC-derivatives.