eBiology: A LifeSciences Journal

  • Journals
  • /
  • eBiology: A LifeSciences Journal

Published in eBiology: A LifeSciences Journal on Sun May 05 2019 14:24:00 GMT-0400 (Eastern Daylight Time)
Vol: 0, No: 0, Page: 0-0
DOI: 10.15562/ebio.null

Therapeutic Efficacy of Cellular Transplantation for Cardiac Repair in iranian patient

Tahereh Kiyani


Full Text

Stem cells are proliferative cells having self-renewal ability. Because of their promising regenerative potential, these cells have been applied to treat number of diseases. According to the US clinical trials registry database (www.clinicaltrials.gov), near about 30,000 clinical studies regarding cell therapy has been registered and stem cells account for 5000 studies. A multitude of factors have been studied carefully like cell homing, viability, engraftment, safety profile, cellular delivery time and retention (3). Poor survival, very low homing, possible teratogenic effect, massive apoptosis of transplanted cells, low cellular retention and viability have questioned the effectiveness of stem cell therapy and controversies flawing its clinical potential are in discussion .

 consectetuer adipiscing elit. Maecenas feugiat consequat diam.

In spite of having such type of limitations, stem cell therapy has gain a monumental advances for a number of clinical problems like cardiac regeneration (Le Huu et al., 2012). Stem cell-based cardiac regeneration is under studies for a wide range of diseases such as acute and chronic ischemic myocardial damage, cardiomyopathy, etc.

Technical developments in last decades to solve cellular transplantation problems have been seen and cells are engineered or modified for enhanced grafting and improved regeneration (Pendyala et al., 2008). Cellular engineering or modifications have gained considerable attention and scientists could developed techniques for enhanced pluripotent behavior, increased stem cell homing and retention etc (Ruvinov et al., 2012).


2. Cardiovascular Problems and Treatments

Cardiovascular diseases (CVD) are the causing 30% global deaths every year. So far, 17 million cases of coronary heart diseases are being registered in United States only, out of which 5.3 have lost their cardiac functions (Loughran et al., 2013). The most common cause of cardiac failure is ischemic heart in which oxygen supply is limited and depletion of adenosine triphosphate (ATP) happens. This cardiac failure occurs in three major steps i) coronary occlusion, 2) angina pectoris and 3) coagulative necrosis (Soonpaa et al., 1994).

CVDs consist of group of diseases that have been shown in Figure 1. This figure also demonstrate US prevalence of each categories.


Cell type



Therapeutic Potential

Potential Advantages



Mesenchymal Stem Cells







1. Can be differentiated towards cardiomyocytes


2. Have clinical agents for cardiac regeneration


3. Multipotent stem cells located in almost all organs of body


1. Have immunomodulatory behavior for allogeneic transplantation


2. Their multi lineage differentiation potential


1. Lineage restriction


2. Cases of bone or cartilage formation in the myocardium


(Dominici et al., 2006; Heng et al., 2009; Gálvez-Montón et al., 2013; Pittenger et al., 1999; da Silva Meirelles et al., 2006; Shake et al., 2002; Amado et al., 2005; Miyahara et al., 2006; Toma et al., 2002)


Embryonic Stem Cells (ESCs)





1. Pluripotent stem cells


2. Efficient cardiogenic differentiation i.e. differentiated cells shown rhythmic beating, action potential etc.


3. Multiple doublings without phenotypic change.


1. Renewable source of donor cardiomyocytes


2. Enhanced integration with the host cardiomyocytes


3. Easy to expand

  1. Isolation of committed ESCs from the undifferentiated ESCs in cell culture


  1. Teratogenicity of ESC-derived cardiomyocytes


  1. Immunogenic and ethical problems



(Xu et al., 2002; Kehat et al., 2001; Kolossov et al., 2006; Johkura et al., 2003)

Cardiac Stem Cells




1. More effective in making new myocardium than stem cells from other organs including the bone marrow


2. Capable to maintain normal cardiac homeostasis

1. Multipotent




3. Without ethical issues


1. Under 1%, CSCs are unable to completely remedy the massive loss of tissue after


2.  Their location in heart is restricted to the right atrium in the adult heart


3. Differentiate towards lineages other than myocardial cells such as endothelial, endocardial, smooth muscle etc (Bi-potent cells).


(Beltrami et al., 2003; Dawn et al., 2005; Linke et al., 2005; Malliaras et al., 2013; Mollova et al., 2013; Laugwitz et al., 2007)





1 - Amado, L. C., Saliaris, A. P., Schuleri, K. H., John, M. S., Xie, J.-S., Cattaneo, S., Durand, D. J., Fitton, T., Kuang, J. Q. & Stewart, G. (2005). Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proceedings of the National Academy of Sciences of the United States of America 102(32): 11474-11479
2 - Bao, C., Guo, J., Lin, G., Hu, M. & Hu, Z. (2008). TNFR gene-modified mesenchymal stem cells attenuate inflammation and cardiac dysfunction following MI. Scandinavian Cardiovascular Journal 42(1): 56-62
3 - Babai, F., Musevi ‐ Aghdam, J., Schurch, W., Royal, A. & Gabbiani, G. (1990). Coexpression of α ‐ sarcomeric actin, α ‐ smooth muscle actin and desmin during myogenesis in rat and mouse embryos I. Skeletal muscle. Differentiation 44(2): 132-142
4 - Bartunek, J., Croissant, J. D., Wijns, W., Gofflot, S., De Lavareille, A., Vanderheyden, M., Kaluzhny, Y., Mazouz, N., Willemsen, P. & Penicka, M. (2007). Pretreatment of adult bone marrow mesenchymal stem cells with cardiomyogenic growth factors and repair of the chronically infarcted myocardium. American Journal of Physiology-Heart and Circulatory Physiology 292(2): H1095-H1104
5 - Bayes-Genis, A., Soler-Botija, C., Farré, J., Sepúlveda, P., Raya, A., Roura, S., Prat-Vidal, C., Gálvez-Montón, C., Montero, J. A. & Büscher, D. (2010). Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents. Journal of molecular and cellular cardiology 49(5): 771-780
6 - Beltrami, A. P., Barlucchi, L., Torella, D., Baker, M., Limana, F., Chimenti, S., Kasahara, H., Rota, M., Musso, E. & Urbanek, K. (2003). Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114(6): 763-776
7 - Breitbach, M., Bostani, T., Roell, W., Xia, Y., Dewald, O., Nygren, J. M., Fries, J. W., Tiemann, K., Bohlen, H. & Hescheler, J. (2007). Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 110(4): 1362-1369
8 - Bull, D. A., Bailey, S. H., Rentz, J. J., Zebrack, J. S., Lee, M., Litwin, S. E. & Kim, S. W. (2003). Effect of Terplex/VEGF-165 gene therapy on left ventricular function and structure following myocardial infarction: VEGF gene therapy for myocardial infarction
9 - Journal of controlled release 93(2): 175-181
10 - Chang, A. C. & Towbin, J. A. (2006). Heart failure in children and young adults: from molecular mechanisms to medical and surgical strategies
11 - WB Saunders Company. Cheng, Z., Ou, L., Zhou, X., Li, F., Jia, X., Zhang, Y., Liu, X., Li, Y., Ward, C. A. & Melo, L. G. (2008). Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Molecular Therapy 16(3): 571-579
12 - da Silva Meirelles, L., Chagastelles, P. C. & Nardi, N. B. (2006). Mesenchymal stem cells reside in virtually all post-natal organs and tissues. Journal of cell science 119(11): 2204-2213
13 - Dai, Y., Xu, M., Wang, Y., Pasha, Z., Li, T. & Ashraf, M. (2007). HIF-1α induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia. Journal of molecular and cellular cardiology 42(6): 1036-1044
14 - Dawn, B., Stein, A. B., Urbanek, K., Rota, M., Whang, B., Rastaldo, R., Torella, D., Tang, X.-L., Rezazadeh, A. & Kajstura, J. (2005). Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proceedings of the National Academy of Sciences of the United States of America 102(10): 3766-3771
15 - del Monte, F., Harding, S. E., Dec, G. W., Gwathmey, J. K. & Hajjar, R. J. (2002). Targeting phospholamban by gene transfer in human heart failure. Circulation 105(8): 904-907
16 - Dib, N., Michler, R. E., Pagani, F. D., Wright, S., Kereiakes, D. J., Lengerich, R., Binkley, P., Buchele, D., Anand, I. & Swingen, C. (2005). Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy four-year follow-up. Circulation 112(12): 1748-1755
17 - Dimarakis, I. (2009). Handbook of cardiac stem cell therapy. Imperial College Press. Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D. & Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4): 315-317
18 - Ennis, I. L., Li, R. A., Murphy, A. M., Marbán, E. & Nuss, H. B. (2002). Dual gene therapy with SERCA1 and Kir2. 1 abbreviates excitation without suppressing contractility. The Journal of clinical investigation 109(109 (3)): 393-400
19 - Etzion, S., Barbash, I. M., Feinberg, M. S., Zarin, P., Miller, L., Guetta, E., Holbova, R., Kloner, R. A., Kedes, L. H. & Leor, J. (2002). Cellular cardiomyoplasty of cardiac fibroblasts by adenoviral delivery of MyoD ex vivo: an unlimited source of cells for myocardial repair
20 - Circulation 106(12 suppl 1): I-125-I-130
21 - Fan, V. H., Au, A., Tamama, K., Littrell, R., Richardson, L. B., Wright, J. W., Wells, A. & Griffith, L. G. (2007). Tethered epidermal growth factor provides a survival advantage to mesenchymal stem cells. Stem Cells 25(5): 1241-1251
22 - Forward, A. I. S. (2007). Preconditioning Stem Cells for Cardiovascular Disease. Circ Res 100: 447-449
23 - Fukuda, K. (2001). Development of regenerative cardiomyocytes from mesenchymal stem cells for cardiovascular tissue engineering. Artificial organs 25(3): 187-193
24 - Fukuyama, N., Tanaka, E., Tabata, Y., Fujikura, H., Hagihara, M., Sakamoto, H., Ando, K., Nakazawa, H. & Mori, H. (2007). Intravenous injection of phagocytes transfected ex vivo with FGF4 DNA/biodegradable gelatin complex promotes angiogenesis in a rat myocardial ischemia/reperfusion injury model. Basic research in cardiology 102(3): 209-216
25 - Gálvez-Montón, C., Prat-Vidal, C., Roura, S., Soler-Botija, C. & Bayes-Genis, A. (2013). Cardiac tissue engineering and the bioartificial heart. Revista Española de Cardiología (English Edition) 66(5): 391-399
26 - Gersh, B. J., Simari, R. D., Behfar, A., Terzic, C. M. & Terzic, A. (2009).Cardiac cell repair therapy: a clinical perspective
27 - In Mayo Clinic Proceedings , Vol. 84, 876-892: Elsevier
28 - Gnecchi, M., Zhang, Z., Ni, A. & Dzau, V. J. (2008). Paracrine mechanisms in adult stem cell signaling and therapy. Circulation research 103(11): 1204-1219
29 - Gonzalez, A., Rota, M., Nurzynska, D., Misao, Y., Tillmanns, J., Ojaimi, C., Padin-Iruegas, M. E., Müller, P., Esposito, G. & Bearzi, C. (2008). Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan. Circulation research 102(5): 597-606
30 - Grauss, R. W., van Tuyn, J., Steendijk, P., Winter, E. M., Pijnappels, D. A., Hogers, B., Groot, G. D., Adriana, C., van der Geest, R. & van der Laarse, A. (2008). Forced myocardin expression enhances the therapeutic effect of human mesenchymal stem cells after transplantation in ischemic mouse hearts. Stem Cells 26(4): 1083-1093
31 - Haider, H. K., Ye, L., Jiang, S., Ge, R., Law, P. K., Chua, T., Wong, P. & Sim, E. K. (2004). Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor. Journal of molecular medicine 82(8): 539-549
32 - Heng, T. S., Dudakov, J. A., Khong, D. M., Chidgey, A. P. & Boyd, R. L. (2009). Stem cells—meet immunity. Journal of molecular medicine 87(11): 1061-1069
33 - Hofmann, M., Wollert, K. C., Meyer, G. P., Menke, A., Arseniev, L., Hertenstein, B., Ganser, A., Knapp, W. H. & Drexler, H. (2005). Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 111(17): 2198-2202
34 - Hough, S. R., Clements, I., Welch, P. J. & Wiederholt, K. A. (2006). Differentiation of Mouse Embryonic Stem Cells after RNA Interference ‐ Mediated Silencing of OCT4 and Nanog. Stem Cells 24(6): 1467-1475
35 - Hu, X., Yu, S. P., Fraser, J. L., Lu, Z., Ogle, M. E., Wang, J.-A. & Wei, L. (2008). Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. The Journal of Thoracic and Cardiovascular Surgery 135(4): 799-808
36 - Huang, J., Guo, J., Beigi, F., Hodgkinson, C. P., Facundo, H. T., Zhang, Z., Espinoza-Derout, J., Zhou, X., Pratt, R. E. & Mirotsou, M. (2014). HASF is a stem cell paracrine factor that activates PKC epsilon mediated cytoprotection. Journal of molecular and cellular cardiology 66: 157-164
37 - Huang, J., Ito, Y., Morikawa, M., Uchida, H., Kobune, M., Sasaki, K., Abe, T. & Hamada, H. (2003). Bcl-xL gene transfer protects the heart against ischemia/reperfusion injury. Biochemical and biophysical research communications 311(1): 64-70
38 - Jefferies, J. L., Price, J. F., Denfield, S. W., Chang, A. C., Dreyer, W. J., McMahon, C. J., Grenier, M. A., Clunie, S. K., Thomas, A. & Moffett, B. S. (2007). Safety and efficacy of nesiritide in pediatric heart failure. Journal of cardiac failure 13(7): 541-548
39 - Jeong, J. H., Kim, S. H., Kim, S. W. & Park, T. G. (2006). Intracellular delivery of poly (ethylene glycol) conjugated antisense oligonucleotide using cationic lipids by formation of self-assembled polyelectrolyte complex micelles. Journal of nanoscience and nanotechnology 6(9-10): 2790-2795
40 - Jo, J.-i., Nagaya, N., Miyahara, Y., Kataoka, M., Harada-Shiba, M., Kangawa, K. & Tabata, Y. (2007). Transplantation of genetically engineered mesenchymal stem cells improves cardiac function in rats with myocardial infarction: benefit of a novel nonviral vector, cationized dextran
41 - Tissue engineering 13(2): 313-322
42 - Johkura, K., Cui, L., Suzuki, A., Teng, R., Kamiyoshi, A., Okamura, S., Kubota, S., Zhao, X., Asanuma, K. & Okouchi, Y. (2003). Survival and function of mouse embryonic stem cell-derived cardiomyocytes in ectopic transplants. Cardiovascular research 58(2): 435-443
43 - Kattman, S. J., Huber, T. L. & Keller, G. M. (2006). Multipotent flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages. Developmental cell 11(5): 723-732
44 - Kehat, I., Kenyagin-Karsenti, D., Snir, M., Segev, H., Amit, M., Gepstein, A., Livne, E., Binah, O., Itskovitz-Eldor, J. & Gepstein, L. (2001). Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. Journal of clinical investigation 108(3): 407
45 - Kim, J., Shapiro, L. & Flynn, A. (2015). The clinical application of mesenchymal stem cells and cardiac stem cells as a therapy for cardiovascular disease. Pharmacology & therapeutics . Kirkton, R. D. & Bursac, N. (2008). Genetic engineering and stem cells: combinatorial approaches for cardiac cell therapy [Cellular/Tissue Engineering]
46 - Engineering in Medicine and Biology Magazine, IEEE 27(3): 85-88
47 - Kolossov, E., Bostani, T., Roell, W., Breitbach, M., Pillekamp, F., Nygren, J. M., Sasse, P., Rubenchik, O., Fries, J. W. & Wenzel, D. (2006). Engraftment of engineered ES cell–derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium. The Journal of experimental medicine 203(10): 2315-2327
48 - Kolossov, E., Lu, Z., Drobinskaya, I., Gassanov, N., Duan, Y., Sauer, H., Manzke, O., Bloch, W., Bohlen, H. & Hescheler, J. (2005). Identification and characterization of embryonic stem cell-derived pacemaker and atrial cardiomyocytes. The FASEB journal 19(6): 577-579
49 - Lanza, R., Langer, R. & Vacanti, J. P. (2011). Principles of tissue engineering. Academic press. Laugwitz, K.-L., Moretti, A., Lam, J., Gruber, P., Chen, Y., Woodard, S., Lin, L.-Z., Cai, C.-L., Lu, M. & Reth, M. (2007). Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 446: 934
50 - Le Huu, A., Prakash, S. & Shum-Tim, D. (2012). Cellular cardiomyoplasty: current state of the field
51 - Regenerative medicine 7(4): 571-582
52 - Léobon, B., Garcin, I., Menasché, P., Vilquin, J.-T., Audinat, E. & Charpak, S. (2003). Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proceedings of the National Academy of Sciences 100(13): 7808-7811
53 - Li, S. C., Wang, L., Jiang, H., Acevedo, J., Chang, A. C. & Loudon, W. G. (2009). Stem cell engineering for treatment of heart diseases: potentials and challenges
54 - Cell biology international 33(3): 255-267
55 - Li, W., Ma, N., Ong, L. L., Nesselmann, C., Klopsch, C., Ladilov, Y., Furlani, D., Piechaczek, C., Moebius, J. M. & Lützow, K. (2007). Bcl ‐ 2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells 25(8): 2118-2127
56 - Lim, S. Y., Kim, Y. S., Ahn, Y., Jeong, M. H., Hong, M. H., Joo, S. Y., Nam, K. I., Cho, J. G., Kang, P. M. & Park, J. C. (2006). The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model. Cardiovascular research 70(3): 530-542
57 - Linke, A., Müller, P., Nurzynska, D., Casarsa, C., Torella, D., Nascimbene, A., Castaldo, C., Cascapera, S., Böhm, M. & Quaini, F. (2005). Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proceedings of the National Academy of Sciences of the United States of America 102(25): 8966-8971
58 - Liu, B., Daviau, J., Nichols, C. N. & Strayer, D. S. (2005). In vivo gene transfer into rat bone marrow progenitor cells using rSV40 viral vectors. Blood 106(8): 2655-2662
59 - Logeart, D., Vinet, L., Ragot, T., Heimburger, M., Louedec, L., Michel, J.-B., Escoubet, B. & Mercadier, J.-J. (2006). Percutaneous intracoronary delivery of SERCA gene increases myocardial function: a tissue Doppler imaging echocardiographic study
60 - American Journal of Physiology-Heart and Circulatory Physiology 291(4): H1773-H1779
61 - Loughran, J. H., Chugh, A. R., Ismail, I. & Bolli, R. (2013). Stem cell therapy: promising treatment in heart failure? Current heart failure reports 10(1)
62 - promising treatment in heart failure? Current heart failure reports 10(1): 73-80
63 - Lungwitz, U., Breunig, M., Blunk, T. & Göpferich, A. (2005). Polyethylenimine-based non-viral gene delivery systems. European Journal of Pharmaceutics and Biopharmaceutics 60(2): 247-266
64 - Lyngbaek, S., Schneider, M., Hansen, J. L. & Sheikh, S. P. (2007). Cardiac regeneration by resident stem and progenitor cells in the adult heart. Basic research in cardiology 102(2): 101-114
65 - Malliaras, K., Zhang, Y., Seinfeld, J., Galang, G., Tseliou, E., Cheng, K., Sun, B., Aminzadeh, M. & Marbán, E. (2013). Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart. EMBO molecular medicine 5(2): 191-209
66 - Mangi, A. A., Noiseux, N., Kong, D., He, H., Rezvani, M., Ingwall, J. S. & Dzau, V. J. (2003). Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nature medicine 9(9): 1195-1201
67 - Markkanen, J. E., Rissanen, T. T., Kivelä, A. & Ylä-Herttuala, S. (2005). Growth factor-induced therapeutic angiogenesis and arteriogenesis in the heart–gene therapy. Cardiovascular research 65(3): 656-664
68 - Marsboom, G. & Janssens, S. (2008). Endothelial progenitor cells: new perspectives and applications in cardiovascular therapies
69 - Marsboom, G., Pokreisz, P., Gheysens, O., Vermeersch, P., Gillijns, H., Pellens, M., Liu, X., Collen, D. & Janssens, S. (2008). Sustained Endothelial Progenitor Cell Dysfunction After Chronic Hypoxia ‐ Induced Pulmonary Hypertension. Stem Cells 26(4): 1017-1026
70 - Matsui, T., Tao, J., del Monte, F., Lee, K.-H., Li, L., Picard, M., Force, T. L., Franke, T. F., Hajjar, R. J. & Rosenzweig, A. (2001). Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation 104(3): 330-335
71 - Mills, W. R., Mal, N., Kiedrowski, M. J., Unger, R., Forudi, F., Popovic, Z. B., Penn, M. S. & Laurita, K. R. (2007). Stem cell therapy enhances electrical viability in myocardial infarction. Journal of molecular and cellular cardiology 42(2): 304-314
72 - Mingliang, R., Bo, Z. & Zhengguo, W. (2011). Stem cells for cardiac repair: status, mechanisms, and new strategies
73 - Stem cells international 2011. Miyahara, Y., Nagaya, N., Kataoka, M., Yanagawa, B., Tanaka, K., Hao, H., Ishino, K., Ishida, H., Shimizu, T. & Kangawa, K. (2006). Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nature medicine 12(4): 459-465
74 - Moffett, B. S. & Chang, A. C. (2006). Future pharmacologic agents for treatment of heart failure in children. Pediatric cardiology 27(5): 533-551
75 - Mollova, M., Bersell, K., Walsh, S., Savla, J., Das, L. T., Park, S.-Y., Silberstein, L. E., dos Remedios, C. G., Graham, D. & Colan, S. (2013). Cardiomyocyte proliferation contributes to heart growth in young humans. Proceedings of the National Academy of Sciences 110(4): 1446-1451
76 - Moretti, A., Caron, L., Nakano, A., Lam, J. T., Bernshausen, A., Chen, Y., Qyang, Y., Bu, L., Sasaki, M. & Martin-Puig, S. (2006). Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127(6): 1151-1165
77 - Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., de Ferranti, S., Despres, J.-P., Fullerton, H. J. & Howard, V. J. (2015). Heart disease and stroke statistics-2015 update: a report from the american heart association
78 - Circulation 131(4): e29
79 - Müller-Ehmsen, J., Whittaker, P., Kloner, R. A., Dow, J. S., Sakoda, T., Long, T. I., Laird, P. W. & Kedes, L. (2002). Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium. Journal of molecular and cellular cardiology 34(2): 107-116
80 - Müller, M., Fleischmann, B., Selbert, S., Ji, G., Endl, E., Middeler, G., Müller, O., Schlenke, P., Frese, S. & Wobus, A. (2000). Selection of ventricular-like cardiomyocytes from ES cells in vitro. The FASEB journal 14(15): 2540-2548
81 - Müller, O. J., Katus, H. A. & Bekeredjian, R. (2007). Targeting the heart with gene therapy-optimized gene delivery methods. Cardiovascular research 73(3): 453-462
82 - Mummery, C. L., Davis, R. P. & Krieger, J. E. (2010). Challenges in using stem cells for cardiac repair. Science translational medicine 2(27): 27ps17-27ps17
83 - Noiseux, N., Gnecchi, M., Lopez-Ilasaca, M., Zhang, L., Solomon, S. D., Deb, A., Dzau, V. J. & Pratt, R. E. (2004). Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation. Molecular Therapy 14(6): 840-850
84 - Nussbaum, J., Minami, E., Laflamme, M. A., Virag, J. A., Ware, C. B., Masino, A., Muskheli, V., Pabon, L., Reinecke, H. & Murry, C. E. (2007). Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response
85 - The FASEB journal 21(7): 1345-1357
86 - Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S. M., Li, B., Pickel, J., McKay, R., Nadal-Ginard, B. & Bodine, D. M. (2001). Bone marrow cells regenerate infarcted myocardium. Nature 410(6829): 701-705
87 - Pasha, Z., Wang, Y., Sheikh, R., Zhang, D., Zhao, T. & Ashraf, M. (2007). Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. Cardiovascular research . Passier, R., van Laake, L. W. & Mummery, C. L. (2008). Stem-cell-based therapy and lessons from the heart. Nature 453(7193): 322-329
88 - Pendyala, L., Goodchild, T., Gadesam, R. R., Chen, J., Robinson, K., Chronos, N. & Hou, D. (2008). Cellular cardiomyoplasty and cardiac regeneration. Current cardiology reviews 4(2): 72
89 - Penn, M. S. (2009). Importance of the SDF-1: CXCR4 axis in myocardial repair
90 - Circulation research 104(10): 1133-1135
91 - Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S. & Marshak, D. R. (1999). Multilineage potential of adult human mesenchymal stem cells. science 284(5411): 143-147
92 - Plotnikov, A. N., Shlapakova, I., Szabolcs, M. J., Danilo, P., Lorell, B. H., Potapova, I. A., Lu, Z., Rosen, A. B., Mathias, R. T. & Brink, P. R. (2007). Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation 116(7): 706-713
93 - Reinecke, H., MacDonald, G. H., Hauschka, S. D. & Murry, C. E. (2000). Electromechanical coupling between skeletal and cardiac muscle implications for infarct repair. The Journal of cell biology 149(3): 731-740
94 - Rinsch, C., Quinodoz, P. D., Pittet Cuenod, B. M., Alizadeh, N., Baetens Baumann, D., Montandon, D., Aebischer, P. & Pepper, M. (2001). Delivery of FGF-2 but not VEGF by encapsulated genetically engineered myoblasts improves survival and vascularization in a model of acute skin flap ischemia. Gene therapy 8(7): 523-533
95 - Roell, W., Lewalter, T., Sasse, P., Tallini, Y. N., Choi, B.-R., Breitbach, M., Doran, R., Becher, U. M., Hwang, S.-M. & Bostani, T. (2007). Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature 450(7171): 819-824
96 - Ruvinov, E., Sapir, Y. & Cohen, S. (2012). Cardiac Tissue Engineering: Principles, Materials, and Applications
97 - Synthesis Lectures on Tissue Engineering 4(1): 1-200
98 - Sakakibara, Y., Nishimura, K., Tambara, K., Yamamoto, M., Lu, F., Tabata, Y. & Komeda, M. (2002). Prevascularization with gelatin microspheres containing basic fibroblast growth factor enhances the benefits of cardiomyocyte transplantation. The Journal of Thoracic and Cardiovascular Surgery 124(1): 50-56
99 - Sanganalmath, S. K. & Bolli, R. (2013). Cell therapy for heart failure a comprehensive overview of experimental and clinical studies, current challenges, and future directions. Circulation research 113(6): 810-834
100 - Segers, V. F. & Lee, R. T. (2008). Stem-cell therapy for cardiac disease. Nature 451(7181): 937-942
101 - Shake, J. G., Gruber, P. J., Baumgartner, W. A., Senechal, G., Meyers, J., Redmond, J. M., Pittenger, M. F. & Martin, B. J. (2002). Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects
102 - The Annals of thoracic surgery 73(6): 1919-1926
103 - Siepe, M., Akhyari, P., Lichtenberg, A., Schlensak, C. & Beyersdorf, F. (2008). Stem cells used for cardiovascular tissue engineering. European Journal of Cardio-Thoracic Surgery 34(2): 242-247
104 - Song, H., Chang, W., Lim, S., Seo, H. S., Shim, C. Y., Park, S., Yoo, K. J., Kim, B. S., Min, B. H. & Lee, H. (2007). Tissue Transglutaminase Is Essential for Integrin ‐ Mediated Survival of Bone Marrow ‐ Derived Mesenchymal Stem Cells. Stem Cells 25(6): 1431-1438
105 - Song, H., Kwon, K., Lim, S., Kang, S.-M., Ko, Y.-G., Xu, Z., Chung, J. H., Kim, B.-S., Lee, H. & Joung, B. (2005). Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions. Molecules and cells 19(3): 402-407
106 - Soonpaa, M. H., Koh, G. Y., Klug, M. G. & Field, L. J. (1994). Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium. science 264(5155): 98-101
107 - Stagg, M. A., Coppen, S. R., Suzuki, K., Varela-Carver, A., Lee, J., Brand, N. J., Fukushima, S., Yacoub, M. H. & Terracciano, C. M. (2006). Evaluation of frequency, type, and function of gap junctions between skeletal myoblasts overexpressing connexin43 and cardiomyocytes: relevance to cell transplantation
108 - The FASEB journal 20(6): 744-746
109 - Sun, L., Cui, M., Wang, Z., Feng, X., Mao, J., Chen, P., Kangtao, M., Chen, F. & Zhou, C. (2007). Mesenchymal stem cells modified with angiopoietin-1 improve remodeling in a rat model of acute myocardial infarction. Biochemical and biophysical research communications 357(3): 779-784
110 - Sun, Q., Zhang, Z. & Sun, Z. (2014). The potential and challenges of using stem cells for cardiovascular repair and regeneration. Genes & Diseases 1(1): 113-119
111 - Takashima, S.-i., Tempel, D. & Duckers, H. J. (2013). Current outlook of cardiac stem cell therapy towards a clinical application. Heart 99(23): 1772-1784
112 - Tang, Y. L., Qian, K., Zhang, Y. C., Shen, L. & Phillips, M. I. (2005a). Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid-mediated stromal-cell-derived factor-1α treatment. Regulatory peptides 125(1): 1-8
113 - Tang, Y. L., Tang, Y., Zhang, Y. C., Qian, K., Shen, L. & Phillips, M. I. (2005b). Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. Journal of the American College of Cardiology 46(7): 1339-1350
114 - Tara, S., Miyamoto, M., Asoh, S., Ishii, N., Yasutake, M., Takagi, G., Takano, T. & Ohta, S. (2007). Transduction of the anti-apoptotic PTD-FNK protein improves the efficiency of transplantation of bone marrow mononuclear cells. Journal of molecular and cellular cardiology 42(3): 489-497
115 - Taylor, D. A., Atkins, B. Z., Hungspreugs, P., Jones, T. R., Reedy, M. C., Hutcheson, K. A., Glower, D. D. & Kraus, W. E. (1998). Regenerating functional myocardium: improved performance after skeletal myoblast transplantation
116 - Nature medicine 4(8): 929-933
117 - Tevaearai, H. T., Brant Walton, G., Keys, J. R., Koch, W. J. & Eckhart, A. D. (2005). Acute ischemic cardiac dysfunction is attenuated via gene transfer of a peptide inhibitor of the β ‐ adrenergic receptor kinase (βARK1). The journal of gene medicine 7(9): 1172-1177
118 - Toma, C., Pittenger, M. F., Cahill, K. S., Byrne, B. J. & Kessler, P. D. (2002). Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105(1): 93-98
119 - Urbanek, K., Torella, D., Sheikh, F., De Angelis, A., Nurzynska, D., Silvestri, F., Beltrami, C. A., Bussani, R., Beltrami, A. P. & Quaini, F. (2005). Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proceedings of the National Academy of Sciences of the United States of America 102(24): 8692-8697
120 - van Tuyn, J., Pijnappels, D. A., de Vries, A. A., de Vries, I., van der Velde-van Dijke, I., Knaän-Shanzer, S., van der Laarse, A., Schalij, M. J. & Atsma, D. E. (2007). Fibroblasts from human postmyocardial infarction scars acquire properties of cardiomyocytes after transduction with a recombinant myocardin gene. The FASEB journal 21(12): 3369-3379
121 - Ward, N. L., Van Slyke, P., Sturk, C., Cruz, M. & Dumont, D. J. (2004). Angiopoietin 1 expression levels in the myocardium direct coronary vessel development. Developmental dynamics 229(3): 500-509
122 - Wei, H., Juhasz, O., Li, J., Tarasova, Y. S. & Boheler, K. R. (2005). Embryonic stem cells and cardiomyocyte differentiation: phenotypic and molecular analyses
123 - Journal of cellular and molecular medicine 9(4): 804-817
124 - Wu, S. M., Fujiwara, Y., Cibulsky, S. M., Clapham, D. E., Lien, C.-l., Schultheiss, T. M. & Orkin, S. H. (2006). Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Cell 127(6): 1137-1150
125 - Xu, C., Police, S., Rao, N. & Carpenter, M. K. (2002). Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circulation research 91(6): 501-508
126 - Xu, P., Li, S. Y., Li, Q., Ren, J., Van Kirk, E. A., Murdoch, W. J., Radosz, M. & Shen, Y. (2006). Biodegradable cationic polyester as an efficient carrier for gene delivery to neonatal cardiomyocytes. Biotechnology and bioengineering 95(5): 893-903
127 - Xu, R., Chen, J., Cong, X., Hu, S. & Chen, X. (2008). Lovastatin protects mesenchymal stem cells against hypoxia ‐ and serum deprivation ‐ induced apoptosis by activation of PI3K/Akt and ERK1/2. Journal of cellular biochemistry 103(1): 256-269
128 - Xue, T., Cho, H. C., Akar, F. G., Tsang, S.-Y., Jones, S. P., Marbán, E., Tomaselli, G. F. & Li, R. A. (2005). Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes insights into the development of cell-based pacemakers. Circulation 111(1): 11-20
129 - Yang, J., Zhou, W., Zheng, W., Ma, Y., Lin, L., Tang, T., Liu, J., Yu, J., Zhou, X. & Hu, J. (2007). Effects of myocardial transplantation of marrow mesenchymal stem cells transfected with vascular endothelial growth factor for the improvement of heart function and angiogenesis after myocardial infarction. Cardiology 107(1): 17-29
130 - Yang, Y.-J., Qian, H.-Y., Huang, J., Li, J.-J., Gao, R.-L., Dou, K.-F., Yang, G.-S., Willerson, J. T. & Geng, Y.-J. (2009). Combined therapy with simvastatin and bone marrow–derived mesenchymal stem cells increases benefits in infarcted swine hearts. Arteriosclerosis, thrombosis, and vascular biology 29(12): 2076-2082
131 - Yang, Z., Ma, D., Wang, W., Xu, S., Zhang, Y., Chen, B., Zhou, F., Zhu, T., Wang, L. & Xu, Z. (2006). Experimental study of bone marrow-derived mesenchymal stem cells combined with hepatocyte growth factor transplantation via noninfarct-relative artery in acute myocardial infarction. Gene therapy 13(22): 1564-1568
132 - Yau, T. M., Kim, C., Li, G., Zhang, Y., Weisel, R. D. & Li, R.-K. (2005). Maximizing ventricular function with multimodal cell-based gene therapy. Circulation 112(9 suppl): I-123-I-128
133 - Ye, L. (2006). Transplantation of Nanoparticle Based Skeletal Myoblasts Over-Expression VEGF-165 for Cardiac Repair. Circulation 114(18 Supplement): II_T
134 - Ye, L., Haider, H. K., Tan, R., Toh, W. C., Law, P. K., Tan, W. B., Su, L., Zhang, W., Ge, R. & Zhang, Y. (2006). Transplantation of nanoparticle based skeletal myoblasts over-expression vascular endothelial growth factor-165 for cardiac repair. Circulation 114(18 Supplement): II_398
135 - Yin, Q., Jin, P., Liu, X., Wei, H., Lin, X., Chi, C., Liu, Y., Sun, C. & Wei, Y. (2011). SDF-1α inhibits hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells through PI3K/Akt and ERK1/2 signaling pathways. Molecular biology reports 38(1): 9-16
136 - Ylä-Herttuala, S. & Martin, J. F. (2000). Cardiovascular gene therapy. The Lancet 355(9199): 213-222
137 - Young, L. S., Searle, P. F., Onion, D. & Mautner, V. (2006). Viral gene therapy strategies: from basic science to clinical application
138 - The Journal of pathology 208(2): 299-318
139 - Zhang, W., Su, X., Gao, Y., Sun, B., Yu, Y., Wang, X. & Zhang, F. (2009). Berberine protects mesenchymal stem cells against hypoxia-induced apoptosis in vitro. Biological and Pharmaceutical Bulletin 32(8): 1335-1342

Article Info

  • Views: 689
  • Downloads: 543
  • Citations: 184

Formats to Cite

  • Full Text PDF
  • Full Text ePUB
  • Full Text XML
  • How to Cite?

Open Access Policy

Copyright © 2018 iMaQPress. Open access article distributed under the Creative Commons Attribution License (CC-BY). For more details, see our Privacy Rules

See Top Similar Articles