Enabling Technologies for Cell-Based Clinical Translation Human Placenta-Derived Adherent Cells Improve Cardiac Performance in Mice With Chronic Heart Failure

Key Words. Placental adherent cell x Mesenchymal stromal cell x Chronic heart failure x Cell therapy Human placenta-derived adherent cells (PDACs) are a culture-expanded, undifferentiated mesenchymal-like population derived from full-term placental tissue, with immunomodulatory, anti-inflammatory, angiogenic, and neuroprotective properties. PDA-001 (cenplacel-L), an intrave-nous formulation of PDAC cells, is in clinical development for the treatment of autoimmune and in-flammatory diseases.We tested the therapeutic effects of PDA-001 inmicewith chronic heart failure (CHF). Three weeks after transaortic constriction surgery to induce CHF, the mice underwent direct intramyocardial (IM) or i.v. injection of PDA-001 at a high (0.53 106 cells per mouse), medium (0.53 105 cells per mouse), or low (0.53 104 cells per mouse) dose. The mice were sacrificed 4 weeks after treatment. Echocardiography and ventricular catheterization showed that IM injection of PDA-001 significantly improved left ventricular systolic and diastolic function compared with injection of ve-hicle or i.v. injection of PDA-001. IM injection of PDA-001 also decreased cardiac fibrosis, shown by trichrome staining in the vicinity of the injection sites. Low-dose treatment showed the best improve-ment in cardiac performance comparedwith themedium- and high-dose groups. In another indepen-dent study to determine themechanismof actionwith bromodeoxyuridine labeling, the proliferation rates of endothelial cells and cardiomyocytes were significantly increased by low ormedium IM dose PDA-001. However, no surviving PDA-001 cells were detected in the heart 1 month after injection. In vivo real-time imaging consistently revealed that the PDA-001 cells were detectable only within 2 days after IM injection of luciferase-expressing PDA-001. Together, these results have demon-strated the cardiac therapeutic potential of PDA-001, likely through a paracrine effect. STEM CELLS TRANSLATIONALMEDICINE 2015;4:269–27