Ischemic heart disease (IHD) accelerates death of cardiomyocytes and leads to the onset of cardiac failure. Due to the application of stem cells, there exists a potential for the regeneration of a damaged myocardium. Here we present a brief review of the modern data on the application of various types of stem cells for the IHD therapy. We consider different types of stem cells, which are most preferable for the clinical application, including mesenchymal stem cells, cardiac stem cells, embryonic stem cells, iPS cells and others. In particular, we discuss their advantages and strategies which can be applied in order to boost their regenerative potential, as well as optimization of their delivery. Besides, our review refers to the contemporary achievements in the field of tissue engineering of heart, using both polymer scaffolds and scaffold-free constructs. We also discuss the most prominent known clinical trials on stem cell therapy of ischemic heart disease.
Lopez, A.D., Mathers, C.D., Ezzati, M., Jamison, D.T. and Murray, C.J. (2006) Global and Regional Burden of Disease and Risk Factors, 2001: Systematic Analysis of Population Health Data. Lancet, 367, 1747-1757. http://dx.doi.org/10.1016/S0140-6736(06)68770-9
Diwan, A. and Dorn II, G.W. (2007) Decompensation of Car-diac Hypertrophy: Cellular Mechanisms and Novel Therapeutic Targets. Physiology, 22, 56-64. http://dx.doi.org/10.1152/physiol.00033.2006
Diwan, A., Krenz, M., Syed, F.M., Wansapura, J., Ren, X., Koesters, A.G., et al. (2007) Inhibition of Ischemic Cardiomyocyte Apoptosis through Targeted Ablation of Bnip3 Restrains Postinfarction Remodeling in Mice. Journal of Clinical Investigation, 117, 2825-2833. http://dx.doi.org/10.1172/JCI32490
Abdel-Latif, A., Bolli, R., Tleyjeh, I.M., Montori, V.M., Perin, E.C., Hornung, C.A., et al. (2007) Adult Bone Marrow-Derived Cells for Cardiac Repair: A Systematic Review and Meta-Analysis. Archives of Internal Medicine, 167, 989-997. http://dx.doi.org/10.1001/archinte.167.10.989
Leri, A., Kajstura, J. and Anversa, P. (2005) Cardiac Stem Cells and Mechanisms of Myocardial Regeneration. Physiological Reviews, 85, 1373-1416. http://dx.doi.org/10.1152/physrev.00013.2005
Borchardt, T. and Braun, T. (2007) Cardiovascular Regeneration in Non-Mammalian Model Systems: What Are the Differences between Newts and Man? Thrombosis and Haemostasis, 98, 311-318. http://dx.doi.org/10.1160/th07-02-0153
Poss, K.D. (2007) Getting to the Heart of Regeneration in Zebrafish. Seminars in Cell & Developmental Biology, 18, 36-45. http://dx.doi.org/10.1016/j.semcdb.2006.11.009
Bergmann, O., Bhardwaj, R.D., Bernard, S., Zdunek, S., Barnabe-Heider, F., Walsh, S., et al. (2009) Evidence for Cardiomyocyte Renewal in Humans. Science, 324, 98-102. http://dx.doi.org/10.1126/science.1164680
Beltrami, A.P., Urbanek, K., Kajstura, J., Yan, S.M., Finato, N., Bussani, R., et al. (2001) Evidence That Human Cardiac Myocytes Divide after MI. The New England Journal of Medicine, 344, 1750-1757. http://dx.doi.org/10.1056/NEJM200106073442303
Ahuja, P., Sdek, P. and MacLellan, W.R. (2007) Cardiac Myocyte Cell Cycle Control in Development, Disease, and Regeneration. Physiological Reviews, 87, 521-544. http://dx.doi.org/10.1152/physrev.00032.2006
Tongers, J., Losordo, D.W. and Landmesser, U. (2011) Stem and Progenitor Cell-Based Therapy in Ischaemic Heart Disease: Promise, Uncertainties, and Challenges. European Heart Journal, 32, 1197-1206. http://dx.doi.org/10.1093/eurheartj/ehr018
Keller, G. (2005) Embryonic Stem Cell Differentiation: Emergence of a New Era in Biology and Medicine. Genes & Development, 19, 1129-1155. http://dx.doi.org/10.1101/gad.1303605
Mummery, C., Ward-van Oostwaard, D., Doevendans, P., Spijker, R., van den Brink, S., Hassink, R., et al. (2003) Differentiation of Human Embryonic Stem Cells to Cardiomyocytes: Role of Coculture with Visceral Endoderm-Like Cells. Circulation, 107, 2733-2740. http://dx.doi.org/10.1161/01.CIR.0000068356.38592.68
Xue, T., Cho, H.C., Akar, F.G., Tsang, S.Y., Jones, S.P., Marban, E., et al. (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, 11-20. http://dx.doi.org/10.1161/01.CIR.0000151313.18547.A2
Caspi, O., Huber, I., Kehat, I., Habib, M., Arbel, G., Gepstein, A., et al. (2007) Transplantation of Human Embryonic Stem Cell-Derived Cardiomyocytes Improves Myocardial Performance in Infarcted Rat Hearts. Journal of the American College of Cardiology, 50, 1884-1893. http://dx.doi.org/10.1016/j.jacc.2007.07.054
Mignone, J.L., Kreutziger, K.L., Paige, S.L. and Murry, C.E. (2010) Cardiogenesis from Human Embryonic Stem Cells. Circulation Journal, 74, 2517-2526. http://dx.doi.org/10.1253/circj.CJ-10-0958
Condorelli, G. and Catalucci, D. (2007) Human Stem Cells for Heart Failure Treatment Ready for Prime Time? Journal of the American College of Cardiology, 50, 1894-1895. http://dx.doi.org/10.1016/j.jacc.2007.07.057
Takahashi, K. and Yamanaka, S. (2006) Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell, 126, 663-676. http://dx.doi.org/10.1016/j.cell.2006.07.024
Zhang, J., Wilson, G.F., Soerens, A.G., Koonce, C.H., Yu, J., Palecek, S.P., et al. (2009) Functional Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells. Circulation Research, 104, e30-e41. http://dx.doi.org/10.1161/circresaha.108.192237
Nelson, T.J., Martinez-Fernandez, A., Yamada, S., Perez-Terzic, C., Ikeda, Y. and Terzic, A. (2009) Repair of Acute MI by Human Stemness Factors Induced Pluripotent Stem Cells. Circulation, 120, 408-416. http://dx.doi.org/10.1161/CIRCULATIONAHA.109.865154
Yoshida, Y. and Yamanaka, S. (2011) IPS Cells: A Source of Cardiac Regeneration. Journal of Molecular and Cellular Cardiology, 50, 327-332. http://dx.doi.org/10.1016/j.yjmcc.2010.10.026
Ieda, M., Fu, J.D., Delgado-Olguin, P., Vedantham, V., Hayashi, Y., Bruneau, B.G., et al. (2010) Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined Factors. Cell, 142, 375-386. http://dx.doi.org/10.1016/j.cell.2010.07.002
Efe, J.A., Hilcove, S., Kim, J., Zhou, H., Ouyang, K., Wang, G., et al. (2011) Conversion of Mouse Fibroblasts into Cardiomyocytes Using a Direct Reprogramming Strategy. Nature Cell Biology, 13, 215-222. http://dx.doi.org/10.1038/ncb2164
Qian, L., Huang, Y., Spencer, C.I., Foley, A., Vedantham, V., Liu, L., et al. (2012) In Vivo Reprogramming of Murine Cardiac Fibroblasts into Induced Cardi-omyocytes. Nature, 485, 593-598. http://dx.doi.org/10.1038/nature11044
Orlic, D., Kajstura, J., Chimenti, S., Limana, F., Jakoniuk, I., Quaini, F., et al. (2001) Mobilized Bone Marrow Cells Repair the Infarcted Heart, Improving Func-tion and Survival. Proceedings of the National Academy of Sciences of the United States of America, 98, 10344-10349. http://dx.doi.org/10.1073/pnas.181177898
Yoon, Y.S., Wecker, A., Heyd, L., Park, J.S., Tkebuchava, T., Kusano, K., et al. (2005) Clonally Expanded Novel Multipotent Stem Cells from Human Bone Marrow Regenerate Myocardium after MI. Journal of Clinical Investigation, 115, 326-338. http://dx.doi.org/10.1172/JCI200522326
Kajstura, J., Rota, M., Whang, B., Cascapera, S., Hosoda, T., Bearzi, C., et al. (2005) Bone Marrow Cells Differentiate in Cardiac Cell Lineages after Infarction Independently of Cell Fusion. Circulation Research, 96, 127-137. http://dx.doi.org/10.1161/01.RES.0000151843.79801.60
Clifford, D.M., Fisher, S.A., Brunskill, S.J., Doree, C., Mathur, A., Watt, S., et al. (2012) Stem Cell Treatment for Acute MI. Cochrane Database of Systematic Reviews, 2, CD006536.
Templin, C., Kotlarz, D., Faulhaber, J., Schnabel, S., Grote, K., Salguero, G., et al. (2008) Ex Vivo Expanded Hematopoietic Progenitor Cells Improve Cardiac Function after MI: Role of Beta-Catenin Transduction and Cell Dose. Journal of Molecular and Cellular Cardiology, 45, 394-403. http://dx.doi.org/10.1016/j.yjmcc.2008.06.010
Mansour, S., Roy, D.C., Bouchard, V., Nguyen, B.K., Stevens, L.M., Gobeil, F., et al. (2010) COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133+ Bone Marrow Stem Cells to Placebo in Patients after Acute MI and Left Ventricular Dysfunction: Study Rationale and Design. Journal of Cardiovascular Translational Research, 3, 153-159. http://dx.doi.org/10.1007/s12265-009-9145-2
Murry, C.E., Soonpaa, M.H., Reinecke, H., Nakajima, H., Nakajima, H.O., Rubart, M., et al. (2004) Haematopoietic Stem Cells Do Not Transdifferentiate into Cardiac Myocytes in Myocardial Infarcts. Nature, 428, 664-668. http://dx.doi.org/10.1038/nature02446
Jujo, K., Ii, M. and Losordo, D.W. (2008) Endothelial Progenitor Cells in Neovascularization of Infarcted Myocardium. Journal of Molecular and Cellular Cardiology, 45, 530-544. http://dx.doi.org/10.1016/j.yjmcc.2008.08.003
Leone, A.M., Rutella, S., Giannico, M.B., Perfetti, M., Zaccone, V., Brugaletta, S., et al. (2008) Effect of Intensive vs Standard Statin Therapy on Endothelial Progenitor Cells and Left Ventricular Function in Patients with Acute MI: Statins for Regeneration after Acute MI and PCI (STRAP) Trial. International Journal of Cardiology, 130, 457-462. http://dx.doi.org/10.1016/j.ijcard.2008.05.036
Gruh, I., Beilner, J., Blomer, U., Schmiedl, A., Schmidt-Richter, I., Kruse, M.L., et al. (2006) No Evidence of Transdifferentiation of Human Endothelial Progenitor Cells into Cardiomyocytes after Coculture with Neonatal Rat Cardiomyocytes. Circulation, 113, 1326-1334. http://dx.doi.org/10.1161/CIRCULATIONAHA.105.559005
Barry, F.P. and Murphy, J.M. (2004) Mesenchymal Stem Cells: Clinical Applications and Biological Characterization. The International Journal of Biochemistry & Cell Biology, 36, 568-584. http://dx.doi.org/10.1016/j.biocel.2003.11.001
Xu, X., Xu, Z., Xu, Y. and Cui, G. (2005) Selective Down-Regulation of Extracellular Matrix Gene Expression by Bone Marrow Derived Stem Cell Transplantation into Infarcted Myocardium. Circulation Journal, 69, 1275-1283. http://dx.doi.org/10.1253/circj.69.1275
Xu, H., Yang, Y.J., Qian, H.Y., Tang, Y.D., Wang, H. and Zhang, Q. (2011) Rosuvastatin Treatment Activates JAK-STAT Pathway and Increases Efficacy of Allogeneic Mesenchymal Stem Cell Transplantation in Infracted Hearts. Circulation Journal, 75, 1476-1485. http://dx.doi.org/10.1253/circj.CJ-10-1275
Aggarwal, S. and Pittenger, M.F. (2005) Human Mesenchymal Stem Cells Modulate Allogeneic Immune Cell Responses. Blood, 105, 1815-1822. http://dx.doi.org/10.1182/blood-2004-04-1559
Makino, S., Fukuda, K., Miyoshi, S., Konishi, F., Kodama, H., Pan, J., Sano, M., Takahashi, T., Hori, S., Abe, H., Hata, J., Umezawa, A. and Ogawa, S. (1999) Cardiomyocytes Can Be Generated from Marrow Stromal Cells in Vitro. Journal of Clinical Investigation, 103, 697-705. http://dx.doi.org/10.1172/JCI5298
Tomita, S., Li, R.K., Weisel, R.D., Mickle, D.A., Kim, E.J., Sakai, T. and Jia, Z.Q. (1999) Autologous Transplantation of Bone Marrow Cells Improves Damaged Heart Function. Circulation, 100, II247-II256. http://dx.doi.org/10.1161/01.cir.100.suppl_2.ii-247
Davani, S., Marandin, A., Mersin, N., Royer, B., Kantelip, B., Hervé, P., Etievent, J.P. and Kantelip, J.P. (2003) Mesenchymal Progenitor Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Rat Cellular Cardiomyoplasty Model. Circulation, 108, II253-II258. http://dx.doi.org/10.1161/01.cir.0000089186.09692.fa
Wang, J.-S., Shum-Tim, D. and Chedrawy, E. (2000) Marrow Stromal Cells for Cellular Cardiomyoplasty: The Importance of Microenvironment for Milieu Dependent Differentiation. Circulation, 102, II-683.
Richardson, J.D., Nelson, A.J., Zannettino, A.C., Gronthos, S., Worthley, S.G. and Psaltis, P.J. (2013) Optimization of the Cardiovascular Therapeutic Properties of Mesenchymal Stromal/Stem Cells-Taking the Next Step. Stem Cell Reviews and Reports, 9, 281-302. http://dx.doi.org/10.1007/s12015-012-9366-7
Silva, G.V., Litovsky, S., Assad, J.A., Sousa, A.L., Martin, B.J., Vela, D., Coulter, S.C., Lin, J., Ober, J., Vaughn, W.K., Branco, R.V., Oliveira, E.M., He, R., Geng, Y.J., Willerson, J.T. and Perin, E.C. (2005) Mesenchymal Stem Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Canine Chronic Ischemia Model. Circulation, 111, 150-156. http://dx.doi.org/10.1161/01.CIR.0000151812.86142.45
Amado, L.C., Saliaris, A.P., Schuleri, K.H., St John, M., Xie, J.S., Cattaneo, S., et al. (2005) Cardiac Repair with IM Injection of Allogeneic Mesenchymal Stem Cells after MI. Proceedings of the National Academy of Sciences of the United States of America, 102, 11474-11479. http://dx.doi.org/10.1073/pnas.0504388102
Gnecchi, M., Zhang, Z., Ni, A. and Dzau, V.J. (2008) Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy. Circulation Research, 103, 1204-1219. http://dx.doi.org/10.1161/CIRCRESAHA.108.176826
Maggini, J., Mirkin, G., Bognanni, I., Holmberg, J., Piazzon, I.M., Nepomnaschy, I., et al. (2010) Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile. PLoS ONE, 5, e9252. http://dx.doi.org/10.1371/journal.pone.0009252
Nemeth, K., Leelahavanichkul, A., Yuen, P.S., Mayer, B., Parmelee, A., Doi, K., et al. (2009) Bone Marrow Stromal Cells Attenuate Sepsis via Prostaglandin E2-Dependent Reprogramming of Host Macrophages to Increase Their Interleukin-10 Production. Nature Medicine, 15, 42-49. http://dx.doi.org/10.1038/nm.1905
Zhang, Q.Z., Su, W.R., Shi, S.H., Wilder-Smith, P., Xiang, A.P., Wong, A., et al. (2010) Human Gingival Derived Mesenchymal Stem Cells Elicit Polarization of m2 Macrophages and Enhance Cutaneous Wound Healing. Stem Cells, 28, 1856-1868. http://dx.doi.org/10.1002/stem.503
Kronsteiner, B., Peterbauer-Scherb, A., Grillari-Voglauer, R., Redl, H., Gabriel, C., van Griensven, M., et al. (2011) Human Mesenchymal Stem Cells and Renal Tubular Epithelial Cells Differentially Influence Monocyte-Derived Dendritic Cell Differentiation and Maturation. Cellular Immunology, 267, 30-38. http://dx.doi.org/10.1016/j.cellimm.2010.11.001
Li, Q., Turdi, S., Thomas, D.P., Zhou, T. and Ren, J. (2010) Intra-Myocardial Delivery of Mesenchymal Stem Cells Ameliorates Left Ventricular and Cardiomyocyte Contractile Dysfunction Following Myocardial Infarction. Toxicology Letters, 195, 119-126. http://dx.doi.org/10.1016/j.toxlet.2010.03.009
Xu, X., Xu, Z., Xu, Y. and Cui, G. (2005) Effects of Mesenchymal Stem Cell Transplantation on Extracellular Matrix after Myocardial Infarction in Rats. Coronary Artery Disease, 16, 245-255. http://dx.doi.org/10.1097/00019501-200506000-00006
Sadat, S., Gehmert, S., Song, Y.-H., Yen, Y., Bai, X., Gaiser, S., et al. (2007) The Cardioprotective Effect of Mesenchymal Stem Cells Is Mediated by IGF-I and VEGF. Biochemical and Biophysical Research Communications, 363, 674-679. http://dx.doi.org/10.1016/j.bbrc.2007.09.058
Madonna, R., Geng, Y.-J. and Caterina, R.D. (2009) Adipose Tissue-Derived Stem Cells Characterization and Potential for Cardiovascular Repair. Arteriosclerosis, Thrombosis, and Vascular Biology, 29, 1723-1729. http://dx.doi.org/10.1161/ATVBAHA.109.187179
Nagaya, N., Fujii, T., Iwase, T., Ohgushi, H., Itoh, T., Uematsu, M., et al. (2004) Intravenous Administration of Mesenchymal Stem Cells Improves Cardiac Function in Rats with Acute Myocardial Infarction through Angiogenesis and Myogenesis. American Journal of Physiology: Heart and Circulatory Physiology, 287, H2670-H2676. http://dx.doi.org/10.1152/ajpheart.01071.2003
Rehman, J., Traktuev, D., Li, J., Merfeld-Clauss, S., Temm-Grove, C.J., Bovenkerk, J.E., et al. (2004) Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells. Circulation, 109, 1292-1298. http://dx.doi.org/10.1161/01.CIR.0000121425.42966.F1
Schenke-Layland, K., Strem, B.M., Jordan, M.C., DeEmedio, M.T., Hedrick, M.H., Roos, K.P., et al. (2009) Adipose Tissue-Derived Cells Improve Cardiac Function Following Myocardial Infarction. Journal of Surgical Research, 153, 217-223. http://dx.doi.org/10.1016/j.jss.2008.03.019
Miyahara, Y., Nagaya, N., Kataoka, M., Yanagawa, B., Tanaka, K., Hao, H., et al. (2006) Monolayered Mesenchymal Stem Cells Repair Scarred Myocardium after Myocardial Infarction. Nature Medicine, 12, 459-465. http://dx.doi.org/10.1038/nm1391
Uemura, R., Xu, M., Ahmad, N. and Ashraf, M. (2006) Bone Marrow Stem Cells Prevent Left Ventricular Remodeling of Ischemic Heart through Paracrine Signaling. Circulation Research, 98, 1414-1421. http://dx.doi.org/10.1161/01.RES.0000225952.61196.39
Bai, X. and Alt, E. (2010) Myocardial Regeneration Potential of Adipose Tissue-Derived Stem Cells. Biochemical and Biophysical Research Communications, 401, 321-326. http://dx.doi.org/10.1016/j.bbrc.2010.09.012
Bai, X., Yan, Y., Song, Y.-H., Sei-densticker, M., Rabinovich, B., Metzele, R., et al. (2010) Both Cultured and Freshly Isolated Adipose Tissue-Derived Stem Cells Enhance Cardiac Function after Acute Myocardial Infarction. European Heart Journal, 31, 489-501. http://dx.doi.org/10.1093/eurheartj/ehp568
Schuleri, K.H., Amado, L.C., Boyle, A.J., Centola, M., Saliaris, A.P., Gutman, M.R., Hatzistergos, K.E., Oskouei, B.N., Zimmet, J.M., Young, R.G., Heldman, A.W., Lardo, A.C. and Hare, J.M. (2008) Early Improvement in Cardiac Tissue Perfusion Due to Mesenchymal Stem Cells. American Journal of Physiolo-gy—Heart and Circulatory Physiology, 294, H2002-H2011. http://ajpheart.physiology.org/content/294/5/H2002.long
Hatzistergos, K.E., Quevedo, H., Oskouei, B.N., Hu, Q., Feigenbaum, G.S., Margitich, I.S., Mazhari, R., Boyle, A.J., Zambrano, J.P., Rodriguez, J.E., Dulce, R., Pattany, P.M., Valdes, D., Revilla, C., Heldman, A.W., McNiece, I. and Hare, J.M. (2010) Bone Marrow Mesenchymal Stem Cells Stimulate Cardiac Stem Cell Proliferation and Differentiation. Circulation Research, 107, 913-922. http://dx.doi.org/10.1161/CIRCRESAHA.110.222703
Katritsis, D.G., Sotiropoulou, P.A., Karvouni, E., Karabinos, I., Korovesis, S., Perez, S.A., et al. (2005) Transcoronary Transplantation of Autologous mesenchymal Stem Cells and Endothelial Progenitors into Infarcted Human Myocardium. Catheterization and Cardiovascular Interventions, 65, 321-329. http://dx.doi.org/10.1002/ccd.20406
Yang, Z., Zhang, F., Ma, W., Chen, B., Zhou, F., Xu, Z., et al. (2010) A Novel Approach to Transplanting Bone Marrow Stem Cells to Repair Human MI: Delivery via a Noninfarct-Relative Artery. Cardiovascular Therapeutics, 28, 380-385. http://dx.doi.org/10.1111/j.1755-5922.2009.00116.x
Chen, S., Liu, Z., Tian, N., Zhang, J., Yei, F., Duan, B., Zhu, Z., Lin, S. and Kwan, T.W. (2006) Intracoronary Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells for Ischemic Cardiomyopathy Due to Isolated Chronic Occluded Left Anterior Descending Artery. The Journal of Invasive Car-diology, 18, 552-556.
Katritsis, D.G., Sotiropoulou, P., Giazitzoglou, E., Karvouni, E. and Papamichail, M. (2007) Electrophysiological Effects of Intracoronary Transplantation of Autologous Mesenchymal and Endothelial Progenitor Cells. Europace, 9, 167-171. http://dx.doi.org/10.1093/europace/eul184
Williams, A.R., Trachtenberg, B., Velazquez, D.L., McNiece, I., Altman, P., Rouy, D., et al. (2011) IM Stem Cell Injection in Patients with Ischemic Cardiomyopathy: Functional Recovery and Reverse Remodeling. Circulation Research, 108, 792-796. http://dx.doi.org/10.1161/CIRCRESAHA.111.242610
Hare, J.M., Traverse, J.H., Henry, T.D., Dib, N., Strumpf, R.K., Schulman, S.P., et al. (2009) A randomized, Double- Blind, Placebo-Controlled, Dose-Escalation Study of Intravenous Adult Human Mesenchymal Stem Cells (Prochymal) after Acute MI. Journal of the American College of Cardiology, 54, 2277-2286. http://dx.doi.org/10.1016/j.jacc.2009.06.055
Fischer, U.M., Harting, M.T., Jimenez, F., Monzon-Posadas, W.O., Xue, H., Savitz, S.I., Laine, G.A. and Cox Jr., C.S. (2009) Pulmonary Passage Is a Major Obstacle for Intravenous Stem Cell Delivery: The Pulmonary First-Pass Effect. Stem Cells and Development, 18, 683-692. http://dx.doi.org/10.1089/scd.2008.0253
Tsyb, A.F., Konoplyannikov, A.G., Kaplan, M.A., et al. (2009) Systemic Transplantation of Autologous Mesenchymal Stem Cells for Coplex Therapy of Patients with Chronic Heart Failure. Cell Transplantology and Tissue Engineering, 4, 78-84.
Guijarro, D., Lebrin, M., Lairez, O., Bourin, P., Piriou, N., Pozzo, J., et al. (2015) 0148: IM Transplantation of Mesenchymal Stromal Cells for Chronic Myocardial Ischemia and Decreased Left Ventricular Function: 1-Year Results of the MESAMI Phase I Clinical Trial. Archives of Cardiovascular Diseases Sup-plements, 7, 20. http://dx.doi.org/10.1016/S1878-6480(15)71543-0
Menasche, P. (2007) Skeletal Myoblasts as a Therapeutic Agent. Progress in Cardiovascular Diseases, 50, 7-17. http://dx.doi.org/10.1016/j.pcad.2007.02.002
Pagani, F.D., DerSimonian, H., Zawadzka, A., Wetzel, K., Edge, A.S., Jacoby, D.B., et al. (2003) Autologous Skeletal Myoblasts Transplanted to Ischemia Damaged Myocardium in Humans: Histological Analysis of Cell Survival and Differentiation. Journal of the American College of Cardiology, 41, 879-888. http://dx.doi.org/10.1016/S0735-1097(03)00081-0
Ghostine, S., Carrion, C., Souza, L.C., Richard, P., Bruneval, P., Vilquin, J.T., et al. (2002) Long-Term Efficacy of Myoblast Transplantation on Regional Structure and Function after MI. Circulation, 106, I131-I136.
Reinecke, H., Poppa, V. and Murry, C.E. (2002) Skeletal Muscle Stem Cells Do Not Transdifferentiate into Cardiomyocytes after Cardiac Grafting. Journal of Molecular and Cellular Cardiology, 34, 241-249. http://dx.doi.org/10.1006/jmcc.2001.1507
Eisen, H.J. (2008) Skeletal Myoblast Transplantation: No Magic Bullet for Ischemic Cardiomyopathy. Nature Clinical Practice Cardiovascular Medicine, 5, 520-521. http://dx.doi.org/10.1038/ncpcardio1299
Oh, H., Bradfute, S.B., Gallardo, T.D., Nakamura, T., Gaussin, V., Mishina, Y., et al. (2003) Cardiac Progenitor Cells from Adult Myocardium: Homing, Differentiation, and Fusion after In-farction. Proceedings of the National Academy of Sciences of the United States of America, 100, 12313-12318. http://dx.doi.org/10.1073/pnas.2132126100
Matsuura, K., Nagai, T., Nishigaki, N., Oyama, T., Nishi, J., Wada, H., et al. (2004) Adult Cardiac Sca-1-Positive Cells Differentiate into Beating Cardiomyocytes. The Journal of Biological Chemistry, 279, 11384-11391. http://dx.doi.org/10.1074/jbc.M310822200
Wang, X., Hu, Q., Nakamura, Y., Lee, J., Zhang, G., From, A.H., et al. (2006) The Role of the Sca-1+/CD31? Cardiac Progenitor Cell Population in Postinfarction Left Ventricular Remodeling. Stem Cells, 24, 1779-1788. http://dx.doi.org/10.1634/stemcells.2005-0386
Beltrami, A.P., Barlucchi, L., Torella, D., Baker, M., Limana, F., Chimenti, S., et al. (2003) Adult Cardiac Stem Cells Are Multipotent and Support Myocardial Regeneration. Cell, 114, 763-776. http://dx.doi.org/10.1016/S0092-8674(03)00687-1
Bolli, R., Chugh, A.R., D’Amario, D., Loughran, J.H., Stoddard, M.F., Ikram, S., et al. (2011) Cardiac Stem Cells in Patients with Ischaemic Cardiomyopathy (SCIPIO): Initial Results of a Randomised Phase 1 Trial. Lancet, 378, 1847-1857. http://dx.doi.org/10.1016/S0140-6736(11)61590-0
Zaruba, M.M., Soonpaa, M., Reuter, S. and Field, L.J. (2010) Cardiomyogenic Potential of c-kit+-Expressing Cells Derived from Neonatal and Adult Mouse Hearts. Circulation, 121, 1992-2000. http://dx.doi.org/10.1161/CIRCULATIONAHA.109.909093
Beltrami, A.P., Barlucchi, L., Torella, D., Baker, M., Limana, F., Chimenti, S., Kasahara, H., Rota, M., Musso, E., Urbanek, K., Leri, A., Kajstura, J., Nadal-Ginard, B. and Anversa, P. (2003) Adult Cardiac Stem Cells Are Multipotent and Support Myocardial Regeneration. Cell, 114, 763-776. http://dx.doi.org/10.1016/S0092-8674(03)00687-1
Dawn, B., Stein, A.B., Urbanek, K., Rota, M., Whang, B., Rastaldo, R., Torella, D., Tang, X.-L., Rezazadeh, A., Kajstura, J., Leri, A., Hunt, G., Varma, J., Prabhu, S.D., Anversa, P. and Bolli, R. (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, 3766-3771. http://dx.doi.org/10.1073/pnas.0405957102
Fazel, S., Cimini, M., Chen, L., Li, S., Angoulvant, D., Fedak, P., et al. (2006) Cardioprotective c-kit+ Cells Are from the Bone Marrow and Regulate the Myocardial Balance of Angiogenic Cytokines. Journal of Clinical Investigation, 116, 1865-1877. http://dx.doi.org/10.1172/JCI27019
Cai, C.L., Liang, X., Shi, Y., Chu, P.H., Pfaff, S.L., Chen, J., et al. (2003) Isl1 Identifies a Cardiac Progenitor Population That Proliferates Prior to Differentiation and Contributes a Majority of Cells to the Heart. Developmental Cell, 5, 877-889. http://dx.doi.org/10.1016/S1534-5807(03)00363-0
Laugwitz, K.L., Moretti, A., Lam, J., Gruber, P., Chen, Y., Woodard, S., et al. (2005) Postnatal Isl1+ Cardioblasts Enter Fully Differentiated Cardiomyocyte Lineages. Nature, 433, 647-653. http://dx.doi.org/10.1038/nature03215
Chien, K.R., Domian, I.J. and Parker, K.K. (2008) Cardiogenesis and the Complex Biology of Regenerative Cardiovascular Medicine. Science, 322, 1494-1497. http://dx.doi.org/10.1126/science.1163267
Laugwitz, K.L., Moretti, A., Caron, L., Nakano, A. and Chien, K.R. (2008) Islet1 Cardiovascular Progenitors: A Single Source for Heart Lineages? Development, 135, 193-205. http://dx.doi.org/10.1242/dev.001883
Martin-Puig, S., Wang, Z. and Chien, K.R. (2008) Lives of a Heart Cell: Tracing the Origins of Cardiac Progenitors. Cell Stem Cell, 2, 320-331. http://dx.doi.org/10.1016/j.stem.2008.03.010
Wu, S.M., Chien, K.R. and Mummery, C. (2008) Origins and Fates of Cardiovascular Progenitor Cells. Cell, 132, 537-543. http://dx.doi.org/10.1016/j.cell.2008.02.002
Kattman, S.J., Huber, T.L. and Keller, G.M. (2006) Multipotent Flk-1+ Cardiovascular Progenitor Cells Give Rise to the Cardiomyocyte, Endothelial, and Vascular Smooth Muscle Lineages. Developmental Cell, 11, 723-732. http://dx.doi.org/10.1016/j.devcel.2006.10.002
Moretti, A., Caron, L., Nakano, A., Lam, J.T., Bernshausen, A., Chen, Y., et al. (2006) Multipotent Embryonic Isl1+ Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification. Cell, 127, 1151-1165. http://dx.doi.org/10.1016/j.cell.2006.10.029
Challen, G.A. and Little, M.H. (2006) A Side Order of Stem Cells: The SP Phenotype. Stem Cells, 24, 3-12. http://dx.doi.org/10.1634/stemcells.2005-0116
Martin, C.M., Meeson, A.P., Robertson, S.M., Hawke, T.J., Rich-ardson, J.A., Bates, S., et al. (2004) Persistent Expression of the ATP-Binding Cassette Transporter, abcg2, Identifies Cardiac SP Cells in the Developing and Adult Heart. Developmental Biology, 265, 262-275. http://dx.doi.org/10.1016/j.ydbio.2003.09.028
Oyama, T., Nagai, T., Wada, H., Naito, A.T., Matsuura, K., Iwanaga, K., et al. (2007) Cardiac Side Population Cells Have a Potential to Migrate and Differentiate into Cardiomyocytes in Vitro and in Vivo. The Journal of Cell Biology, 176, 329-341. http://dx.doi.org/10.1083/jcb.200603014
Messina, E., De Angelis, L., Frati, G., Morrone, S., Chimenti, S., Fiordaliso, F., et al. (2004) Isolation and Expansion of Adult Cardiac Stem Cells from Human and Murine Heart. Circulation Research, 95, 911-921. http://dx.doi.org/10.1161/01.RES.0000147315.71699.51
Takehara, N., Tsutsumi, Y., Tateishi, K., Ogata, T., Tanaka, H., Ueyama, T., et al. (2008) Controlled Delivery of Basic Fibroblast Growth Factor Promotes Human Cardiosphere-Derived Cell Engraftment to Enhance Cardiac Repair for Chronic MI. Journal of the American College of Cardiology, 52, 1858-1865. http://dx.doi.org/10.1016/j.jacc.2008.06.052
Tang, X.L., Rokosh, G., Sanganalmath, S.K., Tokita, Y., Keith, M.C., Shirk, G., Stowers, H., Hunt, G.N., Wu, W., Dawn, B. and Bolli, R. (2015) Effects of Intracoronary Infusion of Escalating Doses of Cardiac Stem Cells in Rats with Acute Myocardial Infarction. Circ Heart Fail, 8, 757-65. http://circheartfailure.ahajournals.org/content/8/4/757.long
Smith, R.R., Barile, L., Cho, H.C., Leppo, M.K., Hare, J.M., Messina, E., et al. (2007) Regenerative Potential of Cardiosphere-Derived Cells Expanded from Percutaneous Endomyocardial Biopsy Specimens. Circulation, 115, 896-908. http://dx.doi.org/10.1161/CIRCULATIONAHA.106.655209
Khan, M., Kwiatkowski, P., Rivera, B.K. and Kup-pusamy, P. (2010) Oxygen and Oxygenation in Stem-Cell Therapy for MI. Life Sciences, 87, 269-274. http://dx.doi.org/10.1016/j.lfs.2010.06.013
Kofoed, H., Sjontoft, E., Siemssen, S.O. and Olesen, H.P. (1985) Bone Marrow Circulation after Osteotomy. Blood Flow, pO2, pCO2, and Pressure Studied in Dogs. Acta Orthopaedica Scandina-vica, 56, 400-403. http://dx.doi.org/10.3109/17453678508994357
Hu, X., Yu, S.P., Fraser, J.L., Lu, Z., Ogle, M.E., Wang, J.-A. and 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 Сardiovascular Surgery, 135, 799-808. http://dx.doi.org/10.1016/j.jtcvs.2007.07.071
Li, J.H., Zhang, N. and Wang, J.A. (2008) Improved Antiapoptotic and Anti-Remodeling Potency of Bone Marrow Mesenchymal Stem Cells by Anoxic Pre-Conditioning in Diabetic Cardiomyopathy. Journal of Endocrinological Investigation, 31, 103-110. http://dx.doi.org/10.1007/BF03345575
Rebelatto, C.K., Aguiar, A.M., Senegaglia, A.C., Aita, C.M., Hansen, P., Barchiki, F., et al. (2009) Expression of Cardiac Function Genes in Adult Stem Cells Is Increased by Treatment with Nitric Oxide Agents. Biochemical and Biophysical Research Communications, 378, 456-461. http://dx.doi.org/10.1016/j.bbrc.2008.11.061
Afzal, M.R., Haider, H., Idris, N.M., Jiang, S., Ahmed, R.P. and Ashraf, M. (2010) Pre-Conditioning Promotes Survival and Angiomyogenic Potential of Mesenchymal Stem Cells in the In-farcted Heart via NF-kappaB Signaling. Antioxidants & Redox Signaling, 12, 693-702. http://dx.doi.org/10.1089/ars.2009.2755
Suzuki, Y., Kim, H.W., Ashraf, M. and Haider, H. (2010) Di-azoxide Potentiates Mesenchymal Stem Cell Survival via NFkappaB-Dependent miR-146a Expression by Targeting Fas. American Journal of Physiology: Heart and Circulatory Physiology, 299, H1077-H1082. http://dx.doi.org/10.1152/ajpheart.00212.2010
Suzuki, K., Smolenski, R.T., Jayakumar, J., Murtuza, B., Brand, N.J. and Yacoub, M.H. (2000) Heat Shock Treatment Enhances Graft Cell Survival in Skeletal Myoblast Transplantation to the Heart. Circulation, 102, III216-III221. http://dx.doi.org/10.1161/01.cir.102.suppl_3.iii-216
Wang, X., Zhao, T., Huang, W., Wang, T., Qian, J., Xu, M., et al. (2009) Hsp20-Engineered Mesenchymal Stem Cells Are Resistant to Oxidative Stress via Enhanced Activation of Akt and Increased Secretion of Growth Factors. Stem Cells, 27, 3021-3031. http://dx.doi.org/10.1002/stem.230
Chang, W., Song, B.-W., Lim, S., Song, H., Shim, C.Y., Cha, M.-J., et al. (2008) Mesenchymal Stem Cells Pretreated with Delivered Hph-1-Hsp70 Protein Are Protected from Hypoxia-Mediated Cell Death and Rescue Heart Functions from Myocardial Injury. Stem Cells, 27, 2283-2292. http://dx.doi.org/10.1002/stem.153
Yang, Y.J., Qian, H.Y., Huang, J., Li, J.-J., Gao, R.-L., Dou, K.-F., et al. (2009) Combined Therapy with Simvastatin and Bone Marrow-Derived Mesenchymal Stem Cells Increases Benefits in Infarcted Swine Hearts. Arteriosclerosis, Thrombosis, and Vascular Biology, 29, 2076-2082. http://dx.doi.org/10.1161/ATVBAHA.109.189662
Yang, Y., Mou, Y., Hu, S.J. and Fu, M. (2009) Beneficial Ef-fect of Rosuvastatin on Cardiac Dysfunction Is Associated with Alterations in Calcium-Regulatory Proteins. European Journal of Heart Failure, 11, 6-13. http://dx.doi.org/10.1093/eurjhf/hfn002
Lin, Y.C., Leu, S., Sun, C.K., Yen, C.-H., Kao, Y.-H., Chang, L.-T., et al. (2010) Early Combined Treatment with Sildenafil and Adipose-Derived Mesenchymal Stem Cells Preserves Heart Function in Rat Dilated Cardiomyopathy. Journal of Translational Medicine, 8, 88. http://dx.doi.org/10.1186/1479-5876-8-88
Haider, H., Lee, Y.J., Jiang, S., Ahmed, R.P., Ryon, M. and Ashraf, M. (2010) Phosphodiesterase Inhibition with Tadalafil Provides Longer and Sustained Protection of Stem Cells. American Journal of Physiology: Heart and Circulatory Physiology, 299, H1395-H1404. http://dx.doi.org/10.1152/ajpheart.00437.2010
Numasawa, Y., Kimura, T., Miyoshi, S., Nishiyama, N., Hida, N., Tsuji, H., Tsuruta, H., Segawa, K., Ogawa, S. and Umezawa, A. (2011) Treatment of Human Mesenchymal Stem Cells with Angiotensin Receptor Blocker Improved Efficiency of Cardiomyogenic Transdifferentiation and Improved Cardiac Function via Angiogenesis. Stem Cells, 29, 1405-1414. http://dx.doi.org/10.1002/stem.691
Wang, Y., Zhang, D., Ashraf, M., Zhao, T., Huang, W., Ashraf, A. and Balasubramaniam, A. (2010) Combining Neuropeptide Y and Mesenchymal Stem Cells Reverses Remodeling after MI. American Journal of Physiology: Heart and Circulatory Physiology, 298, H275-H286. http://dx.doi.org/10.1152/ajpheart.00765.2009
Kinnaird, T., Stabile, E., Burnett, M.S., Shou, M., Lee, C.W., Barr, S., Fuchs, S. and Epstein, S.E. (2004) Local Delivery of Marrow-Derived Stromal Cells Augments Collateral Perfusion through Paracrine Mechanisms. Circulation, 109, 1543-1549. http://dx.doi.org/10.1161/01.CIR.0000124062.31102.57
Pasha, Z., Wang, Y., Sheikh, R., Zhang, D., Zhao, T. and Ashraf, M. (2008) Pre-Conditioning Enhances Cell Survival and Differentiation of Stem Cells during Transplantation in Infarcted Myocardium. Cardiovascular Research, 77, 134-142. http://dx.doi.org/10.1093/cvr/cvm025
Yao, Y., Zhang, F., Wang, L., Zhang, G., Wang, Z., Chen, J. and Gao, X. (2009) Lipopolysaccharide Pre-Conditioning Enhances the Efficacy of Mesenchymal Stem Cells Transplantation in a Rat Model of Acute MI. Journal of Biomedical Science, 16, 74. http://dx.doi.org/10.1186/1423-0127-16-74
Matsumoto, R., Omura, T., Yoshiyama, M., Hayashi, T., Inamoto, S., Koh, K.-R., et al. (2005) Vascular Endothelial Growth Factor-Expressing Mesenchymal Stem Cell Transplantation for the Treatment of Acute MI. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 1168-1173. http://dx.doi.org/10.1161/01.ATV.0000165696.25680.ce
Guo, J., Lin, G., Bao, C., Hu, Z., Chu, H. and Hu, M. (2008) Insulin-Like Growth Factor 1 Improves the Efficacy of Mesenchymal Stem Cells Transplantation in a Rat Model of MI. Journal of Biomedical Science, 15, 89-97. http://dx.doi.org/10.1007/s11373-007-9207-x
Abbott, J.D., Huang, Y., Liu, D., Hickey, R., Krause, D.S. and Giordano, F.J. (2004) Stromal Cell-Derived Factor-1α Plays a Critical Role in Stem Cell Recruitment to the Heart after MI but Is Not Sufficient to Induce Homing in the Absence of Injury. Circulation, 110, 3300-3305. http://dx.doi.org/10.1161/01.CIR.0000147780.30124.CF
Kijowski, J., Baj-Krzyworzeka, M., Majka, M., Reca, R., Marquez, L.A., Christofidou-Solomidou, M., et al. (2001) The SDF-1-CXCR4 Axis Stimulates VEGF Secretion and Activates Integrins but Does Not Affect Proliferation and Survival in Lymphohematopoietic Cells. Stem Cells, 19, 453-466. http://dx.doi.org/10.1634/stemcells.19-5-453
Zhuang, Y., Chen, X., Xu, M., Zhang, L.Y. and Xiang, F. (2009) Chemokine Stromal Cell-Derived Factor 1/CXCL12 Increases Homing of Mesenchymal Stem Cells to Injured Myocardium and Neovascularization Following MI. Chinese Medical Journal, 122, 183-187.
Tang, J., Wang, J., Guo, L., Kong, X., Yang, J., Zheng, F., Zhang, L. and Huang, Y. (2010) Mesenchymal Stem Cells Modified with Stromal Cell-Derived Factor 1 Alpha Improve Cardiac Remodeling via Paracrine Activation of Hepatocyte Growth Factor in a Rat Model of MI. Molecules and Cells, 29, 9-19. http://dx.doi.org/10.1007/s10059-010-0001-7
Guo, Y.H., He, J.G., Wu, J.L., Yang, L., Zhang, D.-S., Tan, X.-Y. and Qi, R.-D. (2008) Hepatocyte Growth Factor and Granulocyte Colony-Stimulating Factor Form a Combined Neovasculogenic Therapy for Ischemic Cardiomyopathy. Cytotherapy, 10, 857-867. http://dx.doi.org/10.1080/14653240802419278
Huang, J., Zhang, Z., Guo, J., Ni, A., Deb, A., Zhang, L., Mirotsou, M., Pratt, R.E. and Dzau, V.J. (2010) Genetic Modification of Mesenchymal Stem Cells Overexpressing CCR1 Increases Cell Viability, Migration, Engraftment, and Capillary Density in the Injured Myocardium. Circulation Research, 106, 1753-1762. http://dx.doi.org/10.1161/CIRCRESAHA.109.196030
Tang, J., Wang, J., Zheng, F., Kong, X., Guo, L., Yang, J., Zhang, L. and Huang, Y. (2010) Combination of Chemokine and Angiogenic Factor Genes and Mesenchymal Stem Cells Could Enhance Angiogenesis and Improve Cardiac Function after Acute MI in Rats. Molecular and Cellular Biochemistry, 339, 107-118. http://dx.doi.org/10.1007/s11010-009-0374-0
Chen, J., Crawford, R., Chen, C. and Xiao, Y. (2013) The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration. Tissue Engineering Part B— Reviews, 19, 516-528. http://online.liebertpub.com/doi/abs/10.1089/ten.TEB.2012.0672
Datta, S.R., Brunet, A. and Greenberg, M.E. (1999) Cellular Survival: A Play in Three Akts. Genes & Development, 13, 2905-2927. http://dx.doi.org/10.1101/gad.13.22.2905
Somanath, P.R., Razorenova, O.V., Chen, J. and Byzova, T.V. (2006) Akt1 in Endothelial Cell and Angiogenesis. Cell Cycle, 5, 512-518. http://dx.doi.org/10.4161/cc.5.5.2538
Gnecchi, M., He, H., Liang, O.D., Melo, L.G., Morello, F., Mu, H., et al. (2005) Paracrine Action Accounts for Marked Protection of Ischemic Heart by Akt Modified Mesenchymal Stem Cells. Nature Medicine, 11, 367-368. http://dx.doi.org/10.1038/nm0405-367
Gnecchi, M., He, H., Noiseux, N., Liang, O.D., Zhang, L., Morello, F., et al. (2006) Evidence Supporting Paracrine Hypothesis for Akt-Modified Mesenchymal Stem Cell-Mediated Cardiac Protection and Functional Improvement. The FASEB Journal, 20, 661-669. http://dx.doi.org/10.1096/fj.05-5211com
Gnecchi, M., He, H., Melo, L.G., Noiseaux, N., Morello, F., de Boer, R.A., et al. (2009) Early Beneficial Effects of Bone Marrow-Derived Mesenchymal Stem Cells Overexpressing Akt on Cardiac Metabolism after MI. Stem Cells, 27, 971-979. http://dx.doi.org/10.1002/stem.12
Mirotsou, M., Zhang, Z., Deb, A., Zhang, L., Gnecchi, M., Noiseux, N., Mu, H., Pachori, A. and Dzau, V. (2007) Secreted Frizzled Related Protein 2 (Sfrp2) Is the Key Akt-Mesenchymal Stem Cellreleased Paracrine Factor Mediating Myocardial Survival and Repair. Proceedings of the National Academy of Sciences of the United States of America, 104, 1643-1648. http://dx.doi.org/10.1073/pnas.0610024104
Song, S.W., Chang, W., Song, B.W., Song, H., Lim, S., Kim, H.-J., et al. (2009) Integrin-Linked Kinase Is Required in Hypoxic Mesenchymal Stem Cells for Strengthening Cell Adhesion to Ischemic Myocardium. Stem Cells, 27, 1358-1365. http://dx.doi.org/10.1002/stem.47
Jiang, Y., Chen, L., Tang, Y., Ma, G., Shen, C., Qi, C., et al. (2010) HO-1 Gene Overexpression Enhances the Beneficial Effects of Superparamagnetic Iron Oxide Labeled Bone Marrow Stromal Cells Transplantation in Swine Hearts Underwent Ischemia/Reperfusion: An MRI Study. Basic Research in Cardiology, 105, 431-442. http://dx.doi.org/10.1007/s00395-009-0079-2
Taljaard, M., Ward, M.R., Kutryk, M.J., Courtman, D.W., Camack, N.J., Goodman, S.G., et al. (2010) Rationale and Design of Enhanced Angiogenic Cell Therapy in Acute MI (ENACT-AMI): The First Randomized Placebo-Controlled Trial of Enhanced Progenitor Cell Therapy for Acute MI. American Heart Journal, 159, 354-360. http://dx.doi.org/10.1016/j.ahj.2009.12.021
Behfar, A., Zingman, L.V., Hodgson, D.M., Rauzier, J.-M., Kane, G.C., Terzic, A. and Pucéat, M. (2002) Stem Cell Differentiation Requires a Paracrine Pathway in the Heart. The FASEB Journal, 16, 1558-1566. http://dx.doi.org/10.1096/fj.02-0072com
Behfar, A., Perez-Terzic, C., Faustino, R.S., Arrell, D.K., Hodgson, D.M., Yamada, S., et al. (2007) Cardiopoietic Programming of Embryonic Stem Cells for Tumor Free Heart Repair. The Journal of Experimental Medicine, 204, 405-420. http://dx.doi.org/10.1084/jem.20061916
Behfar, A., Yamada, S., Crespo-Diaz, R., Nesbitt, J.J., Rowe, L.A., Perez-Terzic, C., et al. (2010) Guided Cardiopoiesis Enhances Therapeutic Benefit of Bone Marrow Human Mesenchymal Stem Cells in Chronic MI. Journal of the American College of Cardiology, 56, 721-734. http://dx.doi.org/10.1016/j.jacc.2010.03.066
Bartunek, J., Wijns, W., Dolatabadi, D., Vanderheyden, M., Dens, J., Ostojic, M., et al. (2011) C-Cure Multicenter Trial: Lineage Specific Bone Marrow Derived Cardiopoietic Mesenchymal Stem Cells for the Treatment of Ischaemic Cardiomyopathy. Journal of the American College of Cardiology, 57, E200. http://dx.doi.org/10.1016/s0735-1097(11)60200-3
Lakshmipathy, U. and Hart, R.P. (2008) Concise Review: Mi-croRNA Expression in Multipotent Mesenchymal Stromal Cells. Stem Cells, 26, 356-363. http://dx.doi.org/10.1634/stemcells.2007-0625
Valtieri, M. and Sorrentino, A. (2008) The Mesenchymal Stromal Cell Contribution to Homeostasis. Journal of Cellular Physiology, 217, 296-300. http://dx.doi.org/10.1002/jcp.21521
Karp, X. and Ambros, V. (2005) Developmental Biology: Encountering mi-croRNAs in Cell Fate Signaling. Science, 310, 1288-1289. http://dx.doi.org/10.1126/science.1121566
Kloosterman, W.P. and Plasterk, R.H. (2006) The Diverse Functions of microRNAs in Animal Development and Disease. Developmental Cell, 11, 441-450. http://dx.doi.org/10.1016/j.devcel.2006.09.009
van Rooij, E., Sutherland, L.B., Liu, N., Williams, A.H., McAnally, J., Gerard, R.D., et al. (2006) A Signature Pattern of Stress-Responsive microRNAs That Can Evoke Cardiac Hypertrophy and Heart Failure. Proceedings of the National Academy of Sciences of the United States of America, 103, 18255-18260. http://dx.doi.org/10.1073/pnas.0608791103
Kim, J., Inoue, K., Ishii, J., Vanti, W.B., Voronov, S.V., Murchison, E., et al. (2007) A microRNA Feedback Circuit in Midbrain Dopamine Neurons. Science, 317, 1220-1224. http://dx.doi.org/10.1126/science.1140481
Calin, G.A. and Croce, C.M. (2006) MicroRNA Signatures in Human Cancers. Nature Reviews Cancer, 6, 857-866. http://dx.doi.org/10.1038/nrc1997
Guo, L., Zhao, R.C. and Wu, Y. (2011) The Role of miRNAs in Self-Renewal and Differentiation of Mesenchymal Stem Cells. Experimental Hematology, 39, 608-616. http://dx.doi.org/10.1016/j.exphem.2011.01.011
Eskildsen, T., Taipaleenm?ki, H., Stenvang, J., Abdallah, B.M., Ditzel, N., Nossent, A.Y., Bak, M., Kauppinen, S. and Kassem, M. (2011) MicroRNA-138 Regulates Osteogenic Differentiation of Human Stromal (Mesenchymal) Stem Cells in Vivo. Proceedings of the National Academy of Sciences of the United States of America, 108, 6139-6144. http://dx.doi.org/10.1073/pnas.1016758108
Yang, Z., Bian, C., Zhou, H., Huang, S., Wang, S., Liao, L. and Zhao, R.C. (2011) MicroRNA Hsa-miR-138 Inhibits Adipogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells through Adenovirus EID-1. Stem Cells and Development, 20, 259-267. http://dx.doi.org/10.1089/scd.2010.0072
Huang, J., Zhao, L., Xing, L. and Chen, D. (2010) MicroRNA-204 Regulates Runx2 Protein Expression and Mesenchymal Progenitor Cell Differentiation. Stem Cells, 28, 357-364.
Zhang, J.F., Fu, W.M., He, M.L., Wang, H., Wang, W.M., Yu, S.C., et al. (2011) MiR-637 Maintains the Balance between Adipocytes and Osteoblasts by Directly Targeting Osterix. Molecular Biology of the Cell, 22, 3955-3961. http://dx.doi.org/10.1091/mbc.E11-04-0356
Shan, Z.X., Lin, Q.X., Yu, X.Y., Deng, C.Y., Li, X.H., Zhang, X.C., Liu, X.Y. and Fu, Y.H. (2007) MicroRNAs Can Be Expressed in Cardiomyocyte-Like Cells Differentiated from Human Mesenchymal Stem Cells. Journal of Southern Medical University, 27, 1813-1816.
Liu, J.L., Jiang, L., Lin, Q.X., Deng, C.Y., Mai, L.P., Zhu, J.N., Li, X.H., Yu, X.Y., Lin, S.G. and Shan, Z.X. (2012) MicroRNA 16 Enhances Differentiation of Human Bone Marrow Mesenchymal Stem Cells in a Cardiac Niche toward Myogenic Phenotypes in Vitro. Life Sciences, 90, 1020-1026. http://dx.doi.org/10.1016/j.lfs.2012.05.011
Psaltis, P.J., Simari, R.D. and Rodriguez-Porcel, M. (2012) Emerging Roles for Integrated Imaging Modalities in Cardiovascular Cell-Based Therapeutics: A Clinical Perspective. European Journal of Nuclear Medicine and Molecular Imaging, 39, 165-181. http://dx.doi.org/10.1007/s00259-011-1925-7
Lunde, K., Solheim, S., Aakhus, S., Arnesen, H., Abdelnoor, M., Egeland, T., et al. (2006) Intracoronary Injection of Mononuclear Bone Marrow Cells in Acute MI. The New England Journal of Medicine, 355, 1199-1209. http://dx.doi.org/10.1056/NEJMoa055706
Schachinger, V., Erbs, S., Elsasser, A., Haberbosch, W., Hambrecht, R., H?lschermann, H., et al. (2006) Intracoronary Bone Marrow-Derived Progenitor Cells in Acute MI. The New England Journal of Medicine, 355, 1210-1221. http://dx.doi.org/10.1056/NEJMoa060186
Traverse, J.H., Henry, T.D., Ellis, S.G., Pepine, C.J., Willerson, J.T., Zhao, D.X.M., et al. (2011) Effect of Intracoronary Delivery of Autologous Bone Marrow Mononuclear Cells 2 to 3 Weeks Following Acute MI on Left Ventricular Function: The LateTIME Randomized Trial. Journal of the American Medical Associ-ation, 306, 2110-2119. http://dx.doi.org/10.1001/jama.2011.1670
Vulliet, P.R., Greeley, M., Halloran, S.M., MacDonald, K.A. and Kittleson, M.D. (2004) Intra-Coronary Arterial Injection of Mesenchymal Stromal Cells and Microinfarction in Dogs. Lancet, 363, 783-784. http://dx.doi.org/10.1016/S0140-6736(04)15695-X
Freyman, T., Polin, G., Osman, H., Crary, J., Lu, M.M., Cheng, L., et al. (2006) A Quantitative, Randomized Study Evaluating Three Methods of Mesenchymal Stem Cell Delivery Following MI. European Heart Journal, 27, 1114-1122. http://dx.doi.org/10.1093/eurheartj/ehi818
Ly, H.Q., Hoshino, K., Pomerantseva, I., Kawase, Y., Yoneyama, R., Takewa, Y., et al. (2009) In Vivo Myocardial Distribution of Multipotent Progenitor Cells Following Intracoronary Delivery in a Swine Model of MI. European Heart Journal, 30, 2861-2868. http://dx.doi.org/10.1093/eurheartj/ehp322
Hou, D., Youssef, E.A., Brinton, T.J., Zhang, P., Rogers, P., Price, E.T., et al. (2005) Radiolabeled Cell Distribution after Intramyocardial, Intracoronary, and Interstitial Retrograde Coronary Venous Delivery: Implications for Current Clinical Trials. Circulation, 112, I150-I156.
Perin, E.C., Silva, G.V., Assad, J.A., Vela, D., Buja, L.M., Sousa, A.L.S., et al. (2008) Comparison of Intracoronary and Transendocardial Delivery of Allogeneic Mesenchymal Cells in a Canine Model of Acute MI. Journal of Molecular and Cellular Cardiology, 44, 486-495. http://dx.doi.org/10.1016/j.yjmcc.2007.09.012
Menasche, P., Hagege, A.A., Vilquin, J.T., Desnos, M., Abergel, E., Pouzet, B., et al. (2003) Autologous Skeletal Myoblast Transplantation for Severe Postinfarction Left Ventricular Dysfunction. Journal of the American College of Cardiology, 41, 1078-1083. http://dx.doi.org/10.1016/S0735-1097(03)00092-5
Mitchell, A.J., Sabondjian, E., Sykes, J., Deans, L., Zhu, W., Lu, X., et al. (2010) Comparison of Initial Cell Retention and Clearance Kinetics after Subendocardial or Subepicardial Injections of Endothelial Progenitor Cells in a Canine MI Model. Journal of Nuclear Medicine, 51, 413-417. http://dx.doi.org/10.2967/jnumed.109.069732
Psaltis, P., Zannettino, A., Gronthos, S. and Worthley, S. (2010) IM Navigation and Mapping for Stem Cell Delivery. Journal of Cardiovascular Translational Research, 3, 135-146. http://dx.doi.org/10.1007/s12265-009-9138-1
Okano, T., Yamada, N., Okuhara, M., Sakai, H. and Sakurai, Y. (1995) Mechanism of Cell Detachment from Temperature-Modulated, Hydrophilic-Hydrophobic Polymer Surfaces. Biomaterials, 16, 297-303. http://dx.doi.org/10.1016/0142-9612(95)93257-E
Shimizu, T., Yamato, M., Isoi, Y., Akutsu, T., Setomaru, T., Abe, K., et al. (2002) Fabrication of Pulsatile Cardiac Tissue Grafts Using a Novel 3-Dimensional Cell Sheet Manipulation Technique and Temperature-Responsive Cell Culture Surfaces. Circulation Research, 90, e40-e48. http://dx.doi.org/10.1161/hh0302.105722
Kofidis, T., Lebl, D.R., Martinez, E.C., Hoyt, G., Tanaka, M. and Robbins, R.C. (2005) Novel Injectable Bioartificial Tissue Facilitates Targeted, Less Invasive, Large-Scale Tissue Restoration on the Beating Heart after Myocardial Injury. Circulation, 112, I173-I177.
Zhang, Y., Thorn, S., DaSilva, J.N., Lamoureux, M., DeKemp, R.A., Beanlands, R.S., et al. (2008) Collagen-Based Matrices Improve the Delivery of Transplanted Circulating Progenitor Cells: Development and Demonstration by ex Vivo Radionuclide Cell Labeling and in Vivo Tracking with Positron-Emission Tomography. Circulation: Cardiovascular Imaging, 1, 197-204. http://dx.doi.org/10.1161/circimaging.108.781120
Dawson, E., Mapili, G., Erickson, K., Taqvi, S. and Roy, K. (2008) Biomaterials for Stem Cell Differentiation. Advanced Drug Delivery Reviews, 60, 215-228. http://dx.doi.org/10.1016/j.addr.2007.08.037
Li, Z. and Guan, J. (2011) Hydrogels for Cardiac Tissue Engineering. Polymers, 3, 740-761. http://dx.doi.org/10.3390/polym3020740
Eschenhagen, T., Fink, C., Remmers, U., Scholz, H., Wattchow, J., Weil, J., et al. (1997) Threedimensional Reconstitution of Embryonic Cardiomyocites in a Collagen Matrix: A New Heart Muscle Model System. The FASEB Journal, 11, 683-694.
Morritt, A.N., Bortolotto, S.K., Dilley, R.J., Han, X., Kompa, A.R., McCombe, D., et al. (2007) Cardiac Tissue Engineering in an in Vivo Vascularized Chamber. Circulation, 115, 353-360. http://dx.doi.org/10.1161/CIRCULATIONAHA.106.657379
Munoz, J., Zhou, Y. and Jarrett, H.W. (2010) LG4-5 Domains of Laminin-211 Binds α-Dystroglycan to Allow Myotube Attachment and Prevent Anoikis. Journal of Cellular Physiology, 222, 111-119. http://dx.doi.org/10.1002/jcp.21927
Eschenhagen, T., Eder, A., Vollert, I. and Hansen, A. (2012) Physiological Aspects of Cardiac Tissue Engineering. American Journal of Physiology: Heart and Circulatory Physiology, 303, H133-H143. http://dx.doi.org/10.1152/ajpheart.00007.2012
Chachques, J.C., Trainini, J.C., Lago, N., Cortes-Morichetti, M., Schussler, O. and Carpentier, A. (2008) Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM trial): Clinical Feasibility Study. The Annals of Thoracic Surgery, 85, 901-908. http://dx.doi.org/10.1016/j.athoracsur.2007.10.052
RECATABI. Regeneration of Cardiac Tissue Assisted by Bioactive Implants. http://cordis.europa.eu/project/rcn/93530_en.html
Laurie, G.W., Horikoshi, S., Killen, P.D., Segui-Real, B. and Yamada, Y. (1989) In Situ Hybridization Reveals Temporal and Spatial Changes in Cellular Expression of mRNA for a Laminin Receptor, Laminin, and Basement Membrane (Type IV) Collagen in the Developing Kidney. The Journal of Cell Biology, 109, 1351-1362. http://dx.doi.org/10.1083/jcb.109.3.1351
Midwood, K.S., Williams, L.V. and Schwarzbauer, J.E. (2004) Tissue Repair and the Dynamics of the Extracellular Matrix. The International Journal of Biochemistry & Cell Biology, 36, 1031-1037. http://dx.doi.org/10.1016/j.biocel.2003.12.003
Bader, A., Schilling, T., Teebken, O.E., Brandes, G., Herden, T., Steinhoff, G., et al. (1998) Tissue Engineering of Heart Valves—Human Endothelial Cell Seeding of Detergent Acellularized Porcine Valves. European Journal Cardio-Thoracic Surgery, 14, 279-284. http://dx.doi.org/10.1016/S1010-7940(98)00171-7
Booth, C., Korossis, S.A., Wilcox, H.E., Watterson, K.G., Kearney, J.N., Fisher, J., et al. (2002) Tissue Engineering of Cardiac Valve Prostheses I: Development and Histological Characterization of an Acellular Porcine Scaffold. The Journal of Heart Valve Disease, 11, 457-462.
Korossis, S.A., Booth, C., Wilcox, H.E., Watterson, K.G., Kearney, J.N., Fisher, J., et al. (2002) Tissue Engineering of Cardiac Valve Prostheses II: Biomechanical Characterization of Decellularized Porcine Aortic Heart Valves. The Journal of Heart Valve Disease, 11, 463-471.
Dahl, S.L., Koh, J., Prabhakar, V. and Niklason, L.E. (2003) Decellularized Native and Engineered Arterial Scaffolds for Transplantation. Cell Transplant, 12, 659-666. http://dx.doi.org/10.3727/000000003108747136
Schmidt, C.E. and Baier, J.M. (2000) Acellular Vascular Tissues: Natural Biomaterials for Tissue Repair and Tissue Engineering. Biomaterials, 21, 2215-2231. http://dx.doi.org/10.1016/S0142-9612(00)00148-4
Ekser, B. and Cooper, D.K. (2010) Overcoming the Barriers to Xenotransplantation: Prospects for the Future. Expert Review of Clinical Immunology, 6, 219-230. http://dx.doi.org/10.1586/eci.09.81