Abstract 205: Cryopreserved Cardiac Tissue Graft (MyCardia) Improved Cardiac Function in Rats With Heart Failure

Abstract

Introduction: There are currently 2M patients with NYHA Class II-IV heart failure of ischemic etiology in the United States. Cell-based therapies hold tremendous potential to provide therapeutic benefit for treating degenerative diseases such as chronic heart failure (CHF). Therapeutic adoption of engineered grafts will require ease of use and demonstration of cost-effectiveness. Here we describe for the first time the ability to cryopreserve an engineered tissue (MyCardia™) and demonstrate functional recovery in a rat model of CHF. Methods: MyCardia grafts were cultured with human dermal fibroblasts (hNDF) and human iPSC derived cardiomyocytes (hiPSC-CMs) (FCDI) into a bioabsorbable mesh (Novus Scientific). Grafts were cryopreserved at -196C for 2-4weeks, thawed, reconstituted and implanted into rats with CHF. Myocardial infarction (MI) were generated in immune competent rats by ligating the left coronary artery. Three weeks after MI, rats received graft implants via median sternotomy. Echocardiography was performed at 3 and 7 weeks post graft implantation. In addition, terminal hemodynamics were performed. Results: MyCardia maintained spontaneous and synchronous contractions pre-freeze (65±10bpm) and post thaw (60±10bpm). Grafts were maintained to 40 days post thaw with no deterioration in composition or beat rate. MyCardia reversed maladaptive left ventricular (LV) remodeling by decreasing (p<0.05) LV volume systole/diastole, LV diameter systole/diastole with trending improvement in EF and FS from 3 and 7 weeks post implantation as compared to CHF controls. Grafts decreased LV end diastolic pressure, 24±6 mmHg vs. 18±3mmHg and showed trending improvements in LV dP/dt(-) and dP/dt(+) as compared to controls. In addition, MyCardia results in 36% reduction in LV EDP operating volume as demonstrated by a leftward shift of the diastolic pressure-volume relationship. Conclusion: MyCardia can be cryopreserved, reconstituted and implanted in rats with CHF. Treated rats demonstrated reversal of maladaptive LV remodeling and continued functional improvement from 3 to 7 weeks post treatment. We anticipate that the ability to cryopreserve will allow long-term storage after large batch manufacture, providing cost and utility advantages.