Cardiac fibroblast-derived 3D extracellular matrix seeded with mesenchymal stem cells as a novel device to transfer cells to the ischemic myocardium

心脏成纤维细胞衍生的 3D 细胞外基质与间充质干细胞结合,作为将细胞转移到缺血心肌的新装置

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作者:Eric G Schmuck, Jacob D Mulligan, Rebecca L Ertel, Nicholas A Kouris, Brenda M Ogle, Amish N Raval, Kurt W Saupe

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.

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.

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

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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