Eric G Schmuck1, Jacob D Mulligan1, Rebecca L Ertel1, Nicholas A Kouris2, Brenda M Ogle2, Amish N Raval3, Kurt W Saupe1. 1. Department of Medicine, University of Wisconsin at Madison, Madison, WI 53706, USA. 2. Department of Biomedical Engineering, University of Wisconsin at Madison, Madison, WI 53706, USA. 3. 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.
Abstract
PURPOSE: Demonstrate a novel manufacturing method to generate extracellular matrix scaffolds from cardiac fibroblasts (CF-ECM) as a therapeutic mesenchymal stem cell-transfer device. MATERIALS AND 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.
PURPOSE: Demonstrate a novel manufacturing method to generate extracellular matrix scaffolds from cardiac fibroblasts (CF-ECM) as a therapeutic mesenchymal stem cell-transfer device. MATERIALS AND 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 mousemyocardial 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.
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