Cardioprotection by placenta-derived stromal cells in a murine myocardial infarction model

• Published in: The Journal of surgical research Vol. 185; no. 1; pp. 70 - 83
• Main Authors: Roy, Rajika, MSC, Brodarac, Andreja, PhD, Kukucka, Marian, MD, Kurtz, Andreas, PhD, Becher, Peter Moritz, MD, Jülke, Kerstin, PhD, Choi, Yeong-Hoon, MD, Pinzur, Lena, MSc, Chajut, Ayelet, PhD, Tschöpe, Carsten, MD, Stamm, Christof, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2013
• Subjects: Angiogenesis; Animals; Cell therapy; Cells, Cultured; Coronary Circulation - physiology; Disease Models, Animal; Echocardiography; Female; Graft Survival; Heart; Humans; Interleukin-10 - blood; Ischemic heart disease infarction; Male; Mice, Inbred BALB C; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - physiopathology; Myocardial Infarction - therapy; Neovascularization, Physiologic - physiology; Paracrine Communication - physiology; Placenta - cytology; Placenta cells; Pregnancy; Stromal Cells - cytology; Stromal Cells - transplantation; Surgery; Transplantation, Heterologous; Heart; Ischemic heart disease infarction; Angiogenesis; Cell therapy; Placenta cells
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2013.05.084

Abstract Background Autologous cells for cell therapy of ischemic cardiomyopathy often display age- and disease-related functional impairment, whereas an allogenic immunotolerant cell product would allow off-the-shelf application of uncompromised donor cells. We investigated the cardiac regeneration potential of a novel, clinical-grade placenta-derived human stromal cell product (PLX-PAD). Methods PLX-PAD cells derived from human donor placentas and expanded in a three-dimensional bioreactor system were tested for surface marker expression, proangiogenic, anti-inflammatory, and immunomodulatory properties in vitro . In BALB/C mice, the left anterior descending artery was ligated and PLX-PAD cells ( n = 10) or vehicle ( n = 10) were injected in the infarct border zone. Four weeks later, heart function was analyzed by two-dimensional and M-mode echocardiography. Scar size, microvessel density, extracellular matrix composition, myocyte apoptosis, and PLX-PAD cell retention were studied by histology. Results In vitro , PLX-PAD cells displayed both proangiogenesis and anti-inflammatory properties, represented by the secretion of both vascular endothelial growth factor and angiopoietin-1 that was upregulated by hypoxia, as well as by the capacity to suppress T-cell proliferation and augment IL-10 secretion when co-cultured with peripheral blood mononuclear cells. Compared with control mice, PLX-PAD-treated hearts had better contractile function, smaller infarct size, greater regional left ventricular wall thickness, and less apoptosis after 4 wk. PLX-PAD stimulated both angiogenesis and arteriogenesis in the infarct border zone, and periostin expression was upregulated in PLX-PAD-treated hearts. Conclusions Clinical-grade PLX-PAD cells exert beneficial effects on ischemic myocardium that are associated with improved contractile function, and may be suitable for further evaluation aiming at clinical pilot trials of cardiac cell therapy.