title: Human placenta-derived adherent cells improve cardiac performance in mice with chronic heart failure.
abstract: 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 intravenous formulation of PDAC cells, is in clinical development for the treatment of autoimmune and inflammatory diseases. We tested the therapeutic effects of PDA-001 in mice with 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 (0.5 × 10(6) cells per mouse), medium (0.5 × 10(5) cells per mouse), or low (0.5 × 10(4) 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 vehicle 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 improvement in cardiac performance compared with the medium- and high-dose groups. In another independent study to determine the mechanism of action with bromodeoxyuridine labeling, the proliferation rates of endothelial cells and cardiomyocytes were significantly increased by low or medium 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 demonstrated the cardiac therapeutic potential of PDA-001, likely through a paracrine effect.
authors: Celgene Cellular Therapeutics, Warren, New Jersey, USA; Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors: Hong-Jung
authors: HJ
authors: Chen
authors: Celgene Cellular Therapeutics, Warren, New Jersey, USA; Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors: Chien-Hsi
authors: CH
authors: Chen
authors: Celgene Cellular Therapeutics, Warren, New Jersey, USA; Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors: Ming-Yao
authors: MY
authors: Chang
authors: Celgene Cellular Therapeutics, Warren, New Jersey, USA; Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors: Da-Ching
authors: DC
authors: Tsai
authors: Celgene Cellular Therapeutics, Warren, New Jersey, USA; Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors: Ellen Z
authors: EZ
authors: Baum
authors: Celgene Cellular Therapeutics, Warren, New Jersey, USA; Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors: Robert
authors: R
authors: Hariri
authors: Celgene Cellular Therapeutics, Warren, New Jersey, USA; Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China phsieh@ibms.sinica.edu.tw uherzberg@celgene.com.
authors: Uri
authors: U
authors: Herzberg
authors: Celgene Cellular Therapeutics, Warren, New Jersey, USA; Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China phsieh@ibms.sinica.edu.tw uherzberg@celgene.com.
authors: Patrick C H
authors: PC
authors: Hsieh
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D064593:Heterografts; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy
keywords: Cell therapy; Chronic heart failure; Mesenchymal stromal cell; Placental adherent cell