The use of human mesenchymal stem cells encapsulated in RGD modified alginate microspheres in the repair of myocardial infarction in the rat.

The combination of scaffold material and cell transplantation therapy has been extensively investigated in cardiac tissue engineering. However, many polymers are difficult to administer or lack the structural integrity to restore LV function. Additionally, polymers need to be biological friendly, favorably influence the microenvironment and increase stem cell retention and survival. This study determined whether human mesenchymal stem cells (hMSCs) encapsulated in RGD modified alginate microspheres are capable of facilitating myocardial repair. The in vitro study of hMSCs demonstrated that the RGD modified alginate can improve cell attachment, growth and increase angiogenic growth factor expression. Alginate microbeads and hMSCs encapsulated in microbeads successfully maintained LV shape and prevented negative LV remodeling after an MI. Cell survival was significantly increased in the encapsulated hMSC group compared with PBS control or cells alone. Microspheres, hMSCs, and hMSCs in microspheres groups reduced infarct area and enhanced arteriole formation. In summary, surface modification and microencapsulation techniques can be combined with cell transplantation leading to the maintenance of LV geometry, preservation of LV function, increase of angiogenesis and improvement of cell survival.

[1]  B. Kulseng,et al.  Alginate-polylysine-alginate microcapsules: effect of size reduction on capsule properties , 2002, Journal of microencapsulation.

[2]  P. Wouters,et al.  Measurement of cardiac function in conscious rats. , 2001, Ultrasound in medicine & biology.

[3]  M. Bissell,et al.  Extracellular matrix signaling: integration of form and function in normal and malignant cells. , 1998, Current opinion in cell biology.

[4]  J. E. Melvik,et al.  Controlling the size of alginate gel beads by use of a high electrostatic potential , 2002, Journal of microencapsulation.

[5]  Randall J Lee,et al.  Injectable fibrin scaffold improves cell transplant survival, reduces infarct expansion, and induces neovasculature formation in ischemic myocardium. , 2004, Journal of the American College of Cardiology.

[6]  A. Carpentier,et al.  Association between a cell-seeded collagen matrix and cellular cardiomyoplasty for myocardial support and regeneration. , 2007, Tissue engineering.

[7]  K. Sawant,et al.  Mucoadhesive microspheres: a promising tool in drug delivery. , 2008, Current drug delivery.

[8]  F. De Ceuninck,et al.  Culture of chondrocytes in alginate beads. , 2004, Methods in molecular medicine.

[9]  G. Aurigemma,et al.  Serial echocardiographic-Doppler assessment of left ventricular geometry and function in rats with pressure-overload hypertrophy. Chronic angiotensin-converting enzyme inhibition attenuates the transition to heart failure. , 1995, Circulation.

[10]  R. Calafiore,et al.  Preparation and in vitro and in vivo characterization of composite microcapsules for cell encapsulation. , 2006, International journal of pharmaceutics.

[11]  Theo Kofidis,et al.  Novel Injectable Bioartificial Tissue Facilitates Targeted, Less Invasive, Large-Scale Tissue Restoration on the Beating Heart After Myocardial Injury , 2005, Circulation.

[12]  Matthew C. Phipps,et al.  The effect of RGD peptides on osseointegration of hydroxyapatite biomaterials. , 2008, Biomaterials.

[13]  H. Blau,et al.  Induction of angiogenesis by implantation of encapsulated primary myoblasts expressing vascular endothelial growth factor , 2000, The journal of gene medicine.

[14]  W. R. Mills,et al.  SDF-1 Recruits Cardiac Stem Cell-Like Cells that Depolarize In Vivo , 2007, Cell transplantation.

[15]  A. Atala,et al.  Controlled release of therapeutic agents: slow delivery and cell encapsulation , 2000, World Journal of Urology.

[16]  G. Dellgren,et al.  Human mesenchymal stem cells do not differentiate into cardiomyocytes in a cardiac ischemic xenomodel , 2006, Annals of medicine.

[17]  R. Weisel,et al.  Increasing transplanted cell survival with cell-based angiogenic gene therapy. , 2005, The Annals of thoracic surgery.

[18]  L. Yao,et al.  Culture of Neural Stem Cells in Calcium Alginate Beads , 2006, Biotechnology progress.

[19]  M. Nasr-Esfahani,et al.  Embryonic Stem Cell Sphere: A Controlled Method for Production of Mouse Embryonic Stem Cell Aggregates for Differentiation , 2008, The International journal of artificial organs.

[20]  R. Haubner.  Alphavbeta3-integrin imaging: a new approach to characterise angiogenesis? , 2006, European journal of nuclear medicine and molecular imaging.

[21]  A R Boccaccini,et al.  Myocardial tissue engineering: a review , 2007, Journal of tissue engineering and regenerative medicine.

[22]  Elazer R Edelman,et al.  Tissue Engineering Therapy for Cardiovascular Disease , 2003, Circulation research.

[23]  Garret D. Nicodemus,et al.  Designing 3D Photopolymer Hydrogels to Regulate Biomechanical Cues and Tissue Growth for Cartilage Tissue Engineering , 2008, Pharmaceutical Research.

[24]  Maythem Saeed,et al.  Restoration of left ventricular geometry and improvement of left ventricular function in a rodent model of chronic ischemic cardiomyopathy. , 2009, The Journal of thoracic and cardiovascular surgery.

[25]  A. Carpentier,et al.  Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Clinical Trial): One Year Follow-Up , 2007, Cell transplantation.

[26]  Roland Haubner,et al.  αvβ3-integrin imaging: a new approach to characterise angiogenesis? , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[27]  Wolfram-Hubertus Zimmermann,et al.  Cardiac Tissue Engineering for Replacement Therapy , 2003, Heart Failure Reviews.

[28]  Y. Kaneda,et al.  Cell Transplantation for the Treatment of Acute Myocardial Infarction Using Vascular Endothelial Growth Factor–Expressing Skeletal Myoblasts , 2001, Circulation.

[29]  A. Bissery,et al.  Enhancement of the functional benefits of skeletal myoblast transplantation by means of coadministration of hypoxia-inducible factor 1alpha. , 2005, The Journal of thoracic and cardiovascular surgery.

[30]  T. Chang.  Pharmaceutical and therapeutic applications of artificial cells including microencapsulation. , 1998, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[31]  Rutger-Jan Swijnenburg,et al.  Comparison of Different Adult Stem Cell Types for Treatment of Myocardial Ischemia , 2008, Circulation.

[32]  N. Boudreau,et al.  Extracellular matrix and integrin signalling: the shape of things to come. , 1999, The Biochemical journal.

[33]  D. Irvine,et al.  Injectable dendritic cell-carrying alginate gels for immunization and immunotherapy. , 2008, Biomaterials.

[34]  F. Veiga,et al.  Alginate microspheres prepared by internal gelation: development and effect on insulin stability. , 2006, International journal of pharmaceutics.

[35]  A. Ho,et al.  Intravenous delivery of autologous mesenchymal stem cells limits infarct size and improves left ventricular function in the infarcted porcine heart. , 2007, Stem cells and development.

[36]  Richard T. Lee,et al.  Self-assembling peptide nanofibers and skeletal myoblast transplantation in infarcted myocardium. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[37]  T. E. Abraham,et al.  Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan--a review. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[38]  Randall J Lee,et al.  Biomaterials for the treatment of myocardial infarction. , 2006, Journal of the American College of Cardiology.

[39]  Yerem Yeghiazarians,et al.  Closed-chest cell injections into mouse myocardium guided by high-resolution echocardiography. , 2005, American journal of physiology. Heart and circulatory physiology.

[40]  M. Simons.  Integrative signaling in angiogenesis , 2004, Molecular and Cellular Biochemistry.

[41]  W. Westlin.  Integrins as targets of angiogenesis inhibition. , 2001, Cancer journal.

[42]  Randall J Lee,et al.  Fibrin glue alone and skeletal myoblasts in a fibrin scaffold preserve cardiac function after myocardial infarction. , 2004, Tissue engineering.

[43]  K. Livak,et al.  Real time quantitative PCR. , 1996, Genome research.

[44]  K. Stormo,et al.  Preparation of Encapsulated Microbial Cells for Environmental Applications , 1992, Applied and environmental microbiology.

[45]  A. Urbanska,et al.  In vitro study of alginate–chitosan microcapsules: an alternative to liver cell transplants for the treatment of liver failure , 2005, Biotechnology Letters.

[46]  M. Ashraf,et al.  Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair. , 2008, Cardiovascular research.

[47]  Loren E Wold,et al.  Thickening of the infarcted wall by collagen injection improves left ventricular function in rats: a novel approach to preserve cardiac function after myocardial infarction. , 2005, Journal of the American College of Cardiology.

[48]  S. Bellis,et al.  The effect of adsorbed serum proteins, RGD and proteoglycan-binding peptides on the adhesion of mesenchymal stem cells to hydroxyapatite. , 2007, Biomaterials.

[49]  Larry Kedes,et al.  Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium. , 2002, Journal of molecular and cellular cardiology.

[50]  T. Chang.  Bioencapsulation in biotechnology. , 1993, Biomaterials, artificial cells, and immobilization biotechnology : official journal of the International Society for Artificial Cells and Immobilization Biotechnology.

[51]  Catarina P Reis,et al.  Review and current status of emulsion/dispersion technology using an internal gelation process for the design of alginate particles , 2006, Journal of microencapsulation.

[52]  Smadar Cohen,et al.  Effect of Injectable Alginate Implant on Cardiac Remodeling and Function After Recent and Old Infarcts in Rat , 2008, Circulation.

[53]  Ngan F Huang,et al.  Injectable biopolymers enhance angiogenesis after myocardial infarction. , 2005, Tissue engineering.

[54]  Charles E. Murry,et al.  Retention and biodistribution of microspheres injected into ischemic myocardium. , 2009, Journal of biomedical materials research. Part A.

[55]  M E Moseley,et al.  A model of acute regional myocardial ischemia and reperfusion in the rat , 1989, Magnetic resonance in medicine.

[56]  R. Lanza,et al.  Xenotransplantation of cells using biodegradable microcapsules. , 1999, Transplantation.

[57]  P. Dell’Era,et al.  Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. , 2005, Cytokine & growth factor reviews.

[58]  Vasif Hasirci,et al.  Sequential growth factor delivery from complexed microspheres for bone tissue engineering. , 2008, Biomaterials.