Abstract 11208: Unexpected Adverse Effect of Mesenchymal Stroma Cell Infusion on Cardiac Function in Doxorubicin-Induced Dilated Cardiomyopathy in Rat
Background: One of the most serious complications of anthracycline therapy in cancer patients is heart failure due to cardiotoxicity and dilated cardiomyopathy (DCM). We aimed to test the hypothesis that IV infusion of mesenchymal stromal cells (MSC), possessing various reparative and regenerative properties, will ameliorate cardiac function in a rat model of anthracyclinic -induced cardiomyopathy.
Methods and Results: Cardiotoxicity and DCM were induced in 40 female Sprague Dawley (SD) rats by weekly intra peritoneal (IP) injections of doxycyclin 3 mg/Kg (cumulative dose 15 mg/Kg for 5 weeks). One week later, the rats were allocated to receive two weekly IV infusions of MSCs (1 x 106), or saline and subsequently monitored for 2 weeks. At the end of doxycyclin therapy, All animals developed DCM, characterized by increase in LV diastolic (0.3±0.007 vs. 0.36±0.007 mm; p<0.001) and systolic area (0.11±0.004 vs. 0.13±0.005 mm; p<0.002), pathological increase in LV mass (0.54±0.01 vs. 0.62±0.02 gr; p<0.0001) and deterioration in fractional shortening (p=0.04). Surprisingly, MSC therapy was associated with further deterioration in fractional shortening (-7.7 ±4.5% vs. 9.7±5.6%, for control, p=0.02), fractional area change (-9.5±3.4% vs. 5.7±3.4%, for control, p=0.004), and increase in LV systolic area vs. control (24.4±9.7% vs. -0.97±6.9%, p=0.04). Interestingly, MSC therapy was associated with preserved kidney function reflected by smaller change in serum creatinine, compared with controls (1±7 vs. 32±16 %, p=0.07).
Conclusions: IV MSC therapy accelerate adverse LV remodeling and dysfunction in anthracyclinic -induced cardiomyopathy in rat. Our findings suggest caution regarding non-selective MSC therapy for anthracyclin-induced DCM.
- © 2011 by American Heart Association, Inc.