title: Cardioprotection by placenta-derived stromal cells in a murine myocardial infarction model.
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.
authors.affiliation: Berlin-Center for Regenerative Therapies (BCRT), Berlin, Germany.
authors.forename: Rajika
authors.initials: R
authors.lastname: Roy
authors.forename: Andreja
authors.initials: A
authors.lastname: Brodarac
authors.forename: Marian
authors.initials: M
authors.lastname: Kukucka
authors.forename: Andreas
authors.initials: A
authors.lastname: Kurtz
authors.forename: Peter Moritz
authors.initials: PM
authors.lastname: Becher
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jülke
authors.forename: Yeong-Hoon
authors.initials: YH
authors.lastname: Choi
authors.forename: Lena
authors.initials: L
authors.lastname: Pinzur
authors.forename: Ayelet
authors.initials: A
authors.lastname: Chajut
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
authors.forename: Christof
authors.initials: C
authors.lastname: Stamm
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003326:Coronary Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D006085:Graft Survival; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008807:Mice, Inbred BALB C; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019899:Paracrine Communication / Q000502:physiology; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation*; D014183:Transplantation, Heterologous
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10
keywords: Angiogenesis; Cell therapy; Heart; Ischemic heart disease infarction; Placenta cells