Mesenchymal stem cell delivery into rat infarcted myocardium using a porous polysaccharide-based scaffold: a quantitative comparison with endocardial injection.

The use of mesenchymal stem cells (MSCs) for tissue regeneration is often hampered by modest engraftment in host tissue. This study was designed to quantitatively compare MSCs engraftment rates after delivery using a polysaccharide-based porous scaffold or endocardial (EC) injection in a rat myocardial infarction model. Cellular engraftment was measured by quantitative reverse transcription-polymerase chain reaction using MSCs previously transduced with a lentiviral vector that expresses green fluorescent protein (GFP). The use of a scaffold promoted local cellular engraftment and survival. The number of residual GFP(+) cells was greater with the scaffold than after EC injection (9.7% vs. 5.1% at 1 month and 16.3% vs. 6.1% at 2 months, respectively [n=5]). This concurred with a significant increase in mRNA vascular endothelial growth factor level in the scaffold group (p<0.05). Clusters of GFP+ cells were detected in the peri-infarct area, mainly phenotypically consistent with immature MSCs. Functional assessment by echocardiography at 2 months postinfarct also showed a trend toward a lower left ventricular dilatation and a reduced fibrosis in the scaffold group in comparison to direct injection group (n=10). These findings demonstrate that using a porous biodegradable scaffold is a promising method to improve cell delivery and engraftment into damaged myocardium.

[1]  H. Yagi,et al.  Cell Delivery: From Cell Transplantation to Organ Engineering , 2010, Cell transplantation.

[2]  Hong Jiang,et al.  Stem cell engineering for treatment of heart diseases: Potentials and challenges , 2009, Cell biology international.

[3]  J. Guan,et al.  Hydrogels for Cardiac Tissue Engineering , 2011 .

[4]  W. Zimmermann,et al.  Embryonic stem cells for cardiac muscle engineering. , 2007, Trends in cardiovascular medicine.

[5]  S. Gronthos,et al.  Concise Review: Mesenchymal Stromal Cells: Potential for Cardiovascular Repair , 2008, Stem cells.

[6]  M. Zviman,et al.  Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. , 2009, European heart journal.

[7]  R. Cichoń,et al.  A new biological membrane for pericardial closure. , 1991, Journal of biomedical materials research.

[8]  A. Hagège,et al.  Factors affecting functional outcome after autologous skeletal myoblast transplantation. , 2001, The Annals of thoracic surgery.

[9]  T. Okano,et al.  Cell sheet engineering for myocardial tissue reconstruction. , 2003, Biomaterials.

[10]  J. Leor,et al.  Bioengineered Cardiac Grafts: A New Approach to Repair the Infarcted Myocardium? , 2000, Circulation.

[11]  F. Chaubet,et al.  Fabrication of porous polysaccharide-based scaffolds using a combined freeze-drying/cross-linking process. , 2010, Acta biomaterialia.

[12]  S. Fazel,et al.  Improvement in cardiac function after bone marrow cell thearpy is associated with an increase in myocardial inflammation. , 2009, American journal of physiology. Heart and circulatory physiology.

[13]  M. Yacoub,et al.  Direct Intramyocardial But Not Intracoronary Injection of Bone Marrow Cells Induces Ventricular Arrhythmias in a Rat Chronic Ischemic Heart Failure Model , 2007, Circulation.

[14]  Yen Chang,et al.  Bioengineered cardiac patch constructed from multilayered mesenchymal stem cells for myocardial repair. , 2008, Biomaterials.

[15]  Hong Liu,et al.  A Tissue Engineering Approach to Progenitor Cell Delivery Results in Significant Cell Engraftment and Improved Myocardial Remodeling , 2007, Stem cells.

[16]  Li Deng,et al.  Repair of infarcted myocardium using mesenchymal stem cell seeded small intestinal submucosa in rabbits. , 2009, Biomaterials.

[17]  R. Cichoń,et al.  Student research award in the hospital intern, resident or clinical fellow Category, 17th Annual Meeting of the Society for Biomaterials, scottsdale, AZ May 1–5,1991. A new biological membrane for pericardial closure , 1991 .

[18]  Lawrence Buja,et al.  Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. , 2008, Journal of molecular and cellular cardiology.

[19]  J. Hubbell,et al.  Human embryonic stem cell-derived microvascular grafts for cardiac tissue preservation after myocardial infarction. , 2011, Biomaterials.

[20]  M. Pfaffl,et al.  A new mathematical model for relative quantification in real-time RT-PCR. , 2001, Nucleic acids research.

[21]  M. Ozeren,et al.  Consequences of PTFE Membrane Used for Prevention of Re-Entry Injuries in Rheumatic Valve Disease , 2002, Cardiovascular surgery.

[22]  David J Mooney,et al.  Cell delivery mechanisms for tissue repair. , 2008, Cell stem cell.

[23]  M. Goumans,et al.  Cell therapy for myocardial regeneration. , 2009, Current molecular medicine.

[24]  I. Verma,et al.  Transgenesis by lentiviral vectors: Lack of gene silencing in mammalian embryonic stem cells and preimplantation embryos , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[25]  F. Chaubet,et al.  The evaluation of a small-diameter polysaccharide-based arterial graft in rats. , 2006, Biomaterials.

[26]  Zhifeng Xiao,et al.  Stem-cell-capturing collagen scaffold promotes cardiac tissue regeneration. , 2011, Biomaterials.

[27]  Robert L Wilensky,et al.  A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. , 2006, European heart journal.

[28]  X. Holy,et al.  Platelet lysates promote mesenchymal stem cell expansion: A safety substitute for animal serum in cell‐based therapy applications , 2005, Journal of cellular physiology.

[29]  R. Johnson,et al.  Induction of cytotoxic T lymphocyte and antibody responses to enhanced green fluorescent protein following transplantation of transduced CD34(+) hematopoietic cells. , 2001, Blood.

[30]  N. Karnik,et al.  Study of leukocytic hydrolytic enzymes in patients with acute stage of coronary heart disease. , 2007, Indian journal of medical sciences.

[31]  Jean-Christophe Ginefri,et al.  High-resolution 1.5-Tesla magnetic resonance imaging for tissue-engineered constructs: a noninvasive tool to assess three-dimensional scaffold architecture and cell seeding. , 2010, Tissue engineering. Part C, Methods.

[32]  Feng Xu,et al.  Engineering hydrogels as extracellular matrix mimics. , 2010, Nanomedicine.

[33]  P. Menasché,et al.  Cell delivery: intramyocardial injections or epicardial deposition? A head-to-head comparison. , 2009, The Annals of thoracic surgery.