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Cardiac Fibroblast-Derived 3D Extracellular Matrix Seeded with Mesenchymal Stem Cells as a Novel Device to Transfer Cells to the Ischemic Myocardium

Abstract

Demonstrate a novel manufacturing method to generate extracellular matrix scaffolds from cardiac fibroblasts (CF-ECM) as a therapeutic mesenchymal stem cell-transfer device. 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 h later, mouse hearts were excised and examined for CF-ECM scaffold retention and cell transfer. 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 h without the use of sutures or glue. Identified hEMSCs were distributed from the epicardium to the endocardium. 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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Acknowledgments

This study was supported by the National Heart, Lung, and Blood Institute grant number 1R21HL092477 and the National Institutes of Health, under Ruth L. Kirschstein National Research Service Award T32 HL 07936 from the National Heart Lung and Blood Institute to the University of Wisconsin-Madison Cardiovascular Research Center.

Conflict of interest

Author ES, Author JM, Author RE, Author NK, Author BO, Author AR, and Author KS declare that they have no conflict of interest.

Animal Studies

All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the University of Wisconsin Madison animal care and use committee.

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Correspondence to Eric G. Schmuck.

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K. W. Saupe died June 23, 2012.

Associate Editor Ajit P. Yoganathan oversaw the review of this article.

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Schmuck, E.G., Mulligan, J.D., Ertel, R.L. et al. Cardiac Fibroblast-Derived 3D Extracellular Matrix Seeded with Mesenchymal Stem Cells as a Novel Device to Transfer Cells to the Ischemic Myocardium. Cardiovasc Eng Tech 5, 119–131 (2014) doi:10.1007/s13239-013-0167-1

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Keywords

  • Cardiac fibroblast
  • Extracellular matrix
  • Stem cell
  • Cardiac
  • Regeneration
  • Heart failure
  • Myocardial infarction