Human Placenta-Derived Adherent Cells Improve Cardiac Performance in Mice With Chronic Heart Failure
| Autor: | Ellen Z. Baum, Hong-Jung Chen, Ming-Yao Chang, Patrick C.H. Hsieh, Uri Herzberg, Robert J. Hariri, Chien-Hsi Chen, Da-Ching Tsai |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Pathology medicine.medical_specialty Cardiac fibrosis health care facilities manpower and services Placenta education Population Cell- and Tissue-Based Therapy Cell therapy Mice Paracrine signalling Pregnancy In vivo health services administration Cell Adhesion medicine Animals Humans Myocytes Cardiac Enabling Technologies for Cell-Based Clinical Translation Heart Failure education.field_of_study business.industry Cell Biology General Medicine medicine.disease medicine.anatomical_structure Heart failure Chronic Disease cardiovascular system Heterografts Female Stem cell business Developmental Biology |
| Zdroj: | Stem Cells Translational Medicine. 4:269-275 |
| ISSN: | 2157-6580 2157-6564 |
| Popis: | 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 × 106 cells per mouse), medium (0.5 × 105 cells per mouse), or low (0.5 × 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 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. |
| Databáze: | OpenAIRE |
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