title: Cardiac fibroblast-derived 3D extracellular matrix seeded with mesenchymal stem cells as a novel device to transfer cells to the ischemic myocardium.
abstract: OBJECTIVE
  Demonstrate a novel manufacturing method to generate extracellular matrix scaffolds from cardiac fibroblasts (CF-ECM) as a therapeutic mesenchymal stem cell-transfer device.
  
  
  METHODS
  Rat CF were cultured at high-density (~1.6×105/cm2) for 10-14 days. Cell sheets were removed from the culture dish by incubation with EDTA and decellularized with water and peracetic acid. CF-ECM was characterized by mass spectrometry, immunofluorescence and scanning electron microscopy. CF-ECM seeded with human embryonic stem cell derived mesenchymal stromal cells (hEMSCs) were transferred into a mouse myocardial infarction model. 48 hours later, mouse hearts were excised and examined for CF-ECM scaffold retention and cell transfer.
  
  
  RESULTS
  CF-ECM scaffolds are composed of fibronectin (82%), collagens type I (13%), type III (3.4%), type V (0.2%), type II (0.1%) elastin (1.3%) and 18 non-structural bioactive molecules. Scaffolds remained intact on the mouse heart for 48 hours without the use of sutures or glue. Identified hEMSCs were distributed from the epicardium to the endocardium.
  
  
  CONCLUSIONS
  High density cardiac fibroblast culture can be used to generate CF-ECM scaffolds. CF-ECM scaffolds seeded with hEMSCs can be maintained on the heart without suture or glue. hEMSC are successfully delivered throughout the myocardium.
authors.affiliation: Department of Medicine, University of Wisconsin at Madison, Madison, WI 53706, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Schmuck
authors.affiliation: Department of Medicine, University of Wisconsin at Madison, Madison, WI 53706, USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Mulligan
authors.affiliation: Department of Medicine, University of Wisconsin at Madison, Madison, WI 53706, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Ertel
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin at Madison, Madison, WI 53706, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kouris
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin at Madison, Madison, WI 53706, USA.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Ogle
authors.affiliation: Department of Medicine, University of Wisconsin at Madison, Madison, WI 53706, USA ; Department of Biomedical Engineering, University of Wisconsin at Madison, Madison, WI 53706, USA.
authors.forename: Amish N
authors.initials: AN
authors.lastname: Raval
authors.affiliation: Department of Medicine, University of Wisconsin at Madison, Madison, WI 53706, USA.
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Saupe
keywords: Cardiac; Cardiac Fibroblast; Extracellular Matrix; Heart Failure; Myocardial Infarction; Regeneration; Stem Cell