Skip to main content

Advertisement

Log in

Cell Delivery Routes for Stem Cell Therapy to the Heart: Current and Future Approaches

  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

An important factor to determine the success of stem cell therapy to the heart is the choice of cell delivery route. This will affect the fate of donor cells and subsequently influence the outcome of treatment; however, there is currently no optimum cell delivery route appropriate for every disease condition or every donor cell type. This review summarises currently available approaches for administering cells to the heart, with a particular focus on cell retention/survival and the therapeutic benefits seen in preclinical and clinical studies. Two major approaches are intracoronary and intramyocardial injection, which have been widely used for the delivery of various types of cells. Although there are advantages to both approaches, donor cell retention and survival are poor using these methods, potentially limiting therapeutic effects. Various attempts to improve current approaches, along with the development of emerging new approaches, are also described and discussed in this review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Siminiak, T., Kalawski, R., Fiszer, D., Jerzykowska, O., Rzezniczak, J., Rozwadowska, N., et al. (2004). Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up. American Heart Journal, 148(3), 531–537.

    Article  PubMed  Google Scholar 

  2. Zhao, Q., Sun, Y., Xia, L., Chen, A., & Wang, Z. (2008). Randomized study of mononuclear bone marrow cell transplantation in patients with coronary surgery. The Annals of Thoracic Surgery, 86(6), 1833–1840.

    Article  PubMed  Google Scholar 

  3. Dib, N., Michler, R. E., Pagani, F. D., Wright, S., Kereiakes, D. J., Lengerich, R., et al. (2005). Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy. Circulation, 112(12), 1748–1755. doi:10.1161/circulationaha.105.547810.

    Article  PubMed  Google Scholar 

  4. Fukushima, S., Coppen, S. R., Lee, J., Yamahara, K., Felkin, L. E., Terracciano, C. M. N., et al. (2008). Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat. PLoS One, 3(8), e3071.

    Article  PubMed  CAS  Google Scholar 

  5. Losordo, D. W., Schatz, R. A., White, C. J., Udelson, J. E., Veereshwarayya, V., Durgin, M., et al. (2007). Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina. Circulation, 115(25), 3165–3172. doi:10.1161/circulationaha.106.687376.

    Article  PubMed  Google Scholar 

  6. Brasselet, C., Morichetti, M. C., Messas, E., Carrion, C., Bissery, A., Bruneval, P., et al. (2005). Skeletal myoblast transplantation through a catheter-based coronary sinus approach: an effective means of improving function of infarcted myocardium. European Heart Journal, 26(15), 1551–1556. doi:10.1093/eurheartj/ehi151.

    Article  PubMed  Google Scholar 

  7. Thompson, C. A., Nasseri, B. A., Makower, J., Houser, S., McGarry, M., Lamson, T., et al. (2003). Percutaneous transvenous cellular cardiomyoplasty—a novel nonsurgical approach for myocardial cell transplantation. Journal of the American College of Cardiology, 41(11), 1964–1971. doi:10.1016/s0735-1097(03)00397-8.

    Article  PubMed  Google Scholar 

  8. Ikeno, F., Lyons, J., Kaneda, H., Baluom, M., Benet, L. Z., & Rezaee, M. (2004). Novel percutaneous adventitial drug delivery system for regional vascular treatment. Catheterization and Cardiovascular Interventions, 63(2), 222–230.

    Article  PubMed  Google Scholar 

  9. Penn, M. S., Ellis, S., Gandhi, S., Greenbaum, A., Hodes, Z., Mendelsohn, F. O., et al. (2012). Adventitial delivery of an allogeneic bone marrow-derived adherent stem cell in acute myocardial infarction: phase I clinical study. Circulation Research, 110(2), 304–311.

    Article  PubMed  CAS  Google Scholar 

  10. Medicetty, S., Wiktor, D., Lehman, N., Raber, A., Popovic, Z. B., Deans, R., et al. (2012). Percutaneous adventitial delivery of allogeneic bone marrow derived stem cells via infarct related artery improves long-term ventricular function in acute myocardial infarction. Cell Transplant. doi:10.3727/096368911x603657.

  11. 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(9 Suppl), I150–I156.

    PubMed  Google Scholar 

  12. George, J. C., Goldberg, J., Joseph, M., Abdulhameed, N., Crist, J., Das, H., et al. (2008). Transvenous intramyocardial cellular delivery increases retention in comparison to intracoronary delivery in a porcine model of acute myocardial infarction. Journal of Interventional Cardiology, 21(5), 424–431.

    Article  PubMed  Google Scholar 

  13. Perin, E. C., Silva, G. V., Assad, J. A. R., 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 myocardial infarction. Journal of Molecular and Cellular Cardiology, 44(3), 486–495.

    Article  PubMed  CAS  Google Scholar 

  14. Suzuki, K., Murtuza, B., Beauchamp, J. R., Brand, N. J., Barton, P. J., Varela-Carver, A., et al. (2004). Role of interleukin-1beta in acute inflammation and graft death after cell transplantation to the heart. Circulation, 110(11 Suppl 1), II219–II224. doi:10.1161/01.CIR.0000138388.55416.06.

    PubMed  Google Scholar 

  15. Suzuki, K., Murtuza, B., Beauchamp, J. R., Smolenski, R. T., Varela-Carver, A., Fukushima, S., et al. (2004). Dynamics and mediators of acute graft attrition after myoblast transplantation to the heart. The FASEB Journal. doi:10.1096/fj.03-1308fje. 03-1308fje.

  16. ukushima, S., Varela-Carver, A., Coppen, S. R., Yamahara, K., Felkin, L. E., Lee, J., et al. (2007). Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model. Circulation, 115(17), 2254–2261. doi:10.1161/CIRCULATIONAHA.106.662577.

    Article  PubMed  Google Scholar 

  17. Veltman, C. E., Soliman, O. I. I., Geleijnse, M. L., Vletter, W. B., Smits, P. C., ten Cate, F. J., et al. (2008). Four-year follow-up of treatment with intramyocardial skeletal myoblasts injection in patients with ischaemic cardiomyopathy. European Heart Journal, 29(11), 1386–1396. doi:10.1093/eurheartj/ehn171.

    Article  PubMed  Google Scholar 

  18. Coppen, S. R., Fukushima, S., Shintani, Y., Takahashi, K., Varela-Carver, A., Salem, H., et al. (2008). A factor underlying late-phase arrhythmogenicity after cell therapy to the heart: global downregulation of connexin43 in the host myocardium after skeletal myoblast transplantation. Circulation, 118(14 Suppl), S138–S144. doi:10.1161/CIRCULATIONAHA.107.779629.

    Article  PubMed  CAS  Google Scholar 

  19. Menasche, P., Alfieri, O., Janssens, S., McKenna, W., Reichenspurner, H., Trinquart, L., et al. (2008). The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation, 117(9), 1189–1200. doi:10.1161/CIRCULATIONAHA.107.734103.

    Article  PubMed  Google Scholar 

  20. Donndorf, P., Kundt, G., Kaminski, A., Yerebakan, C., Liebold, A., Steinhoff, G., et al. (2011). Intramyocardial bone marrow stem cell transplantation during coronary artery bypass surgery: a meta-analysis. The Journal of Thoracic and Cardiovascular Surgery, 142(4), 911–920.

    Article  PubMed  Google Scholar 

  21. Arom, K. V., Ruengsakulrach, P., & Jotisakulratana, V. (2008). Intramyocardial angiogenic cell precursor injection for cardiomyopathy. Asian Cardiovascular and Thoracic Annals, 16(2), 143–148.

    PubMed  Google Scholar 

  22. Ota, T., Patronik, N. A., Schwartzman, D., Riviere, C. N., & Zenati, M. A. (2008). Minimally invasive epicardial injections using a novel semiautonomous robotic device. Circulation, 118(14 suppl 1), S115–S120. doi:10.1161/circulationaha.107.756049.

    Article  PubMed  Google Scholar 

  23. Lee, W.-Y., Wei, H.-J., Lin, W.-W., Yeh, Y.-C., Hwang, S.-M., Wang, J.-J., et al. (2011). Enhancement of cell retention and functional benefits in myocardial infarction using human amniotic-fluid stem-cell bodies enriched with endogenous ECM. Biomaterials, 32(24), 5558–5567.

    Article  PubMed  CAS  Google Scholar 

  24. Huang, N. F., Yu, J., Sievers, R., Li, S., & Lee, R. J. (2005). Injectable biopolymers enhance angiogenesis after myocardial infarction. Tissue Engineering, 11(11–12), 1860–1866.

    Article  PubMed  CAS  Google Scholar 

  25. Christman, K. L., Vardanian, A. J., Fang, Q., Sievers, R. E., Fok, H. H., & Lee, R. J. (2004). Injectable fibrin scaffold improves cell transplant survival, reduces infarct expansion, and induces neovasculature formation in ischemic myocardium. Journal of the American College of Cardiology, 44(3), 654–660.

    Article  PubMed  CAS  Google Scholar 

  26. Nakamuta, J. S., Danoviz, M. E., Marques, F. L. N., dos Santos, L., Becker, C., Goncalves, G. A., et al. (2009). Cell therapy attenuates cardiac dysfunction post myocardial infarction: effect of timing, routes of injection and a fibrin scaffold. PLoS One, 4(6), e6005.

    Article  PubMed  CAS  Google Scholar 

  27. Strauer, B. E., Brehm, M., Zeus, T., Gattermann, N., Hernandez, A., Sorg, R. V., et al. (2001). Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Deutsche Medizinische Wochenschrift, 126(34–35), 932–938.

    Article  PubMed  CAS  Google Scholar 

  28. Tuma, J., Fernanadez-Vina, R., Carrasco, A., Castillo, J., Cruz, C., Carrillo, A., et al. (2011). Safety and feasibility of percutaneous retrograde coronary sinus delivery of autologous bone marrow mononuclear cell transplantation in patients with chronic refractory angina. Journal of Translational Medicine, 9(1), 183. doi:10.1186/1479-5876-9-183.

    Article  PubMed  Google Scholar 

  29. Moreira Rde, C., Haddad, A. F., Silva, S. A., Souza, A. L., Tuche, F. A., Oliveira, M. A., et al. (2011). Intracoronary stem-cell injection after myocardial infarction: microcirculation sub-study. Arquivos Brasileiros de Cardiologia, 97(5), 420–426.

    Article  PubMed  Google Scholar 

  30. 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. doi:10.1161/hc0102.101442.

    Article  PubMed  Google Scholar 

  31. Freyman, T., Polin, G., Osman, H., Crary, J., Lu, M., Cheng, L., et al. (2006). A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. European Heart Journal, 27(9), 1114–1122.

    Article  PubMed  Google Scholar 

  32. Goussetis, E., Manginas, A., Koutelou, M., Peristeri, I., Theodosaki, M., Kollaros, N., et al. (2006). Intracoronary infusion of CD133 Selected autologous bone marrow progenitor cells in patients with chronic ischemic cardiomyopathy: cell isolation, adherence to the infarcted area, and body distribution. Stem Cells, 24(10), 2279–2283.

    Article  PubMed  CAS  Google Scholar 

  33. Fukushima, S., Campbell, N. G., Coppen, S. R., Yamahara, K., Yuen, A. H. Y., Smolenski, R. T., et al. (2011). Quantitative assessment of initial retention of bone marrow mononuclear cells injected into the coronary arteries. The Journal of Heart and Lung Transplantation, 30(2), 227–233. doi:10.1016/j.healun.2010.09.002.

    Article  PubMed  Google Scholar 

  34. Doyle, B., Kemp, B. J., Chareonthaitawee, P., Reed, C., Schmeckpeper, J., Sorajja, P., et al. (2007). Dynamic tracking during intracoronary injection of 18F-FDG-labeled progenitor cell therapy for acute myocardial infarction. Journal of Nuclear Medicine, 48(10), 1708–1714. doi:10.2967/jnumed.107.042838.

    Article  PubMed  Google Scholar 

  35. Vulliet, P. R., Greeley, M., Halloran, S. M., MacDonald, K. A., & Kittleson, M. D. (2004). Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet, 363(9411), 783–784. doi:10.1016/S0140-6736(04)15695-X.

    Article  PubMed  Google Scholar 

  36. Schachinger, V., Erbs, S., Elsasser, A., Haberbosch, W., Hambrecht, R., Holschermann, H., et al. (2006). Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. The New England Journal of Medicine, 355(12), 1210–1221.

    Article  PubMed  CAS  Google Scholar 

  37. Assmus, B., Rolf, A., Erbs, S., Elsasser, A., Haberbosch, W., Hambrecht, R., et al. (2010). Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction. Circulation. Heart Failure, 3(1), 89–96. doi:10.1161/circheartfailure.108.843243.

    Article  PubMed  Google Scholar 

  38. Clifford, D. M., Fisher, S. A., Brunskill, S. J., Doree, C., Mathur, A., Watt, S., et al. (2012). Stem cell treatment for acute myocardial infarction. Cochrane Database of Systematic Reviews, 2, CD006536.

    Google Scholar 

  39. Konstam, M. A., Rousseau, M. F., Kronenberg, M. W., Udelson, J. E., Melin, J., Stewart, D., et al. (1992). Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. SOLVD investigators. Circulation, 86(2), 431–438.

    Article  PubMed  CAS  Google Scholar 

  40. Seth, S., Bhargava, B., Narang, R., Ray, R., Mohanty, S., Gulati, G., et al. (2010). The ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) Trial: a long-term follow-up study. Journal of the American College of Cardiology, 55(15), 1643–1644.

    Article  PubMed  Google Scholar 

  41. Jaiswal, R. K., Jaiswal, N., Bruder, S. P., Mbalaviele, G., Marshak, D. R., & Pittenger, M. F. (2000). Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. Journal of Biological Chemistry, 275(13), 9645–9652. doi:10.1074/jbc.275.13.9645.

    Article  PubMed  CAS  Google Scholar 

  42. 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. The Lancet, 378(9806), 1847–1857.

    Article  Google Scholar 

  43. Makkar, R. R., Smith, R. R., Cheng, K., Malliaras, K., Thomson, L. E. J., Berman, D., et al. (2012). Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. The Lancet, 379(9819), 895–904.

    Article  Google Scholar 

  44. Tossios, P., Krausgrill, B., Schmidt, M., Fischer, T., Halbach, M., Fries, J. W., et al. (2008). Role of balloon occlusion for mononuclear bone marrow cell deposition after intracoronary injection in pigs with reperfused myocardial infarction. European Heart Journal, 29(15), 1911–1921.

    Article  PubMed  CAS  Google Scholar 

  45. Yao, K., Huang, R., Sun, A., Qian, J., Liu, X., Ge, L., et al. (2009). Repeated autologous bone marrow mononuclear cell therapy in patients with large myocardial infarction. European Journal of Heart Failure, 11(7), 691–698. doi:10.1093/eurjhf/hfp062.

    Article  PubMed  Google Scholar 

  46. Gu, X. A., Xie, Y., Gu, J. A., Sun, L., He, S. H., Xu, R. X., et al. (2011). Repeated intracoronary infusion of peripheral blood stem cells with G-CSF in patients with refractory ischemic heart failure—a pilot study. Circulation Journal, 75(4), 955–963. doi:10.1253/circj.CJ-10-0898.

    Article  PubMed  Google Scholar 

  47. Kang, H.-J., Lee, H.-Y., Na, S.-H., Chang, S.-A., Park, K.-W., Kim, H.-K., et al. (2006). Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: the MAGIC Cell-3-DES randomized, controlled trial. Circulation, 114(1_suppl), I-145–I-151. doi:10.1161/circulationaha.105.001107.

    Article  Google Scholar 

  48. Pasha, Z., Wang, Y., Sheikh, R., Zhang, D., Zhao, T., & Ashraf, M. (2008). Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. Cardiovascular Research, 77(1), 134–142. doi:10.1093/cvr/cvm025.

    Article  PubMed  CAS  Google Scholar 

  49. Pons, J., Huang, Y., Arakawa-Hoyt, J., Washko, D., Takagawa, J., Ye, J., et al. (2008). VEGF improves survival of mesenchymal stem cells in infarcted hearts. Biochemical and Biophysical Research Communications, 376(2), 419–422.

    Article  PubMed  CAS  Google Scholar 

  50. Ryzhov, S., Solenkova, N. V., Goldstein, A. E., Lamparter, M., Fleenor, T., Young, P. P., et al. (2008). Adenosine receptor-mediated adhesion of endothelial progenitors to cardiac microvascular endothelial cells. Circulation Research, 102(3), 356–363. doi:10.1161/circresaha.107.158147.

    Article  PubMed  CAS  Google Scholar 

  51. Aicher, A., Brenner, W., Zuhayra, M., Badorff, C., Massoudi, S., Assmus, B., et al. (2003). Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation, 107(16), 2134–2139. doi:10.1161/01.CIR.0000062649.63838.C9.

    Article  PubMed  Google Scholar 

  52. Forest, V. F., Tirouvanziam, A. M., Perigaud, C., Fernandes, S., Fusellier, M. S., Desfontis, J. C., et al. (2010). Cell distribution after intracoronary bone marrow stem cell delivery in damaged and undamaged myocardium: implications for clinical trials. Stem Cell Research and Therapy, 1(1), 4. doi:10.1186/scrt4.

    Article  PubMed  CAS  Google Scholar 

  53. Brenner, W., Aicher, A., Eckey, T., Massoudi, S., Zuhayra, M., Koehl, U., et al. (2004). 111In-labeled CD34+ hematopoietic progenitor cells in a rat myocardial infarction model. Journal of Nuclear Medicine, 45(3), 512–518.

    PubMed  CAS  Google Scholar 

  54. Kang, W. J., Kang, H. J., Kim, H. S., Chung, J. K., Lee, M. C., & Lee, D. S. (2006). Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction. Journal of Nuclear Medicine, 47(8), 1295–1301.

    PubMed  Google Scholar 

  55. 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 myocardial infarction. Journal of the American College of Cardiology, 54(24), 2277–2286.

    Article  PubMed  CAS  Google Scholar 

  56. 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(6), H2670–H2676. doi:10.1152/ajpheart.01071.2003.

    Article  PubMed  CAS  Google Scholar 

  57. Kraitchman, D. L., Tatsumi, M., Gilson, W. D., Ishimori, T., Kedziorek, D., Walczak, P., et al. (2005). Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation, 112(10), 1451–1461. doi:10.1161/CIRCULATIONAHA.105.537480.

    Article  PubMed  Google Scholar 

  58. Chiu, L. L., Iyer, R. K., Reis, L. A., Nunes, S. S., & Radisic, M. (2012). Cardiac tissue engineering: current state and perspectives. Frontiers in Bioscience: a Journal and Virtual Library, 17, 1533–1550.

    Article  CAS  Google Scholar 

  59. Elloumi-Hannachi, I., Yamato, M., & Okano, T. (2010). Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine. Journal of Internal Medicine, 267(1), 54–70.

    Article  PubMed  CAS  Google Scholar 

  60. Yang, J., Yamato, M., Kohno, C., Nishimoto, A., Sekine, H., Fukai, F., et al. (2005). Cell sheet engineering: recreating tissues without biodegradable scaffolds. Biomaterials, 26(33), 6415–6422.

    Article  PubMed  CAS  Google Scholar 

  61. Sekine, H., Shimizu, T., Kosaka, S., Kobayashi, E., & Okano, T. (2006). Cardiomyocyte bridging between hearts and bioengineered myocardial tissues with mesenchymal transition of mesothelial cells. The Journal of Heart and Lung Transplantation: the Official Publication of the International Society for Heart Transplantation, 25(3), 324–332.

    Article  Google Scholar 

  62. 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(4), 459–465.

    Article  PubMed  CAS  Google Scholar 

  63. Matsuura, K., Honda, A., Nagai, T., Fukushima, N., Iwanaga, K., Tokunaga, M., et al. (2009). Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice. The Journal of Clinical Investigation, 119(8), 2204–2217.

    PubMed  CAS  Google Scholar 

  64. Bel, A., Planat-Bernard, V., Saito, A., Bonnevie, L., Bellamy, V., Sabbah, L., et al. (2010). Composite cell sheets: a further step toward safe and effective myocardial regeneration by cardiac progenitors derived from embryonic stem cells. Circulation, 122(11 suppl 1), S118–S123. doi:10.1161/circulationaha.109.927293.

    Article  PubMed  Google Scholar 

  65. Memon, I. A., Sawa, Y., Fukushima, N., Matsumiya, G., Miyagawa, S., Taketani, S., et al. (2005). Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets. The Journal of Thoracic and Cardiovascular Surgery, 130(5), 1333–1341.

    Article  PubMed  Google Scholar 

  66. Miyagawa, S., Saito, A., Sakaguchi, T., Yoshikawa, Y., Yamauchi, T., Imanishi, Y., et al. (2010). Impaired myocardium regeneration with skeletal cell sheets—a preclinical trial for tissue-engineered regeneration therapy. Transplantation, 90(4), 364–372. doi:10.1097/TP.0b013e3181e6f201.

    Article  PubMed  Google Scholar 

  67. Yeo, C., & Mathur, A. (2009). Autologous bone marrow-derived stem cells for ischemic heart failure: REGENERATE-IHD trial. Regenerative Medicine, 4(1), 119–127.

    Article  PubMed  Google Scholar 

  68. Stamm, C., Kleine, H.-D., Choi, Y. H., Dunkelmann, S., Lauffs, J. A., Lorenzen, B., et al. (2007). Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. The Journal of Thoracic and Cardiovascular Surgery, 133(3), 717–725.

    Article  PubMed  Google Scholar 

  69. Patel, A. N., Geffner, L., Vina, R. F., Saslavsky, J., Urschel, H. C., Kormos, R., et al. (2005). Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study. The Journal of Thoracic and Cardiovascular Surgery, 130(6), 1631–1638.

    Article  PubMed  Google Scholar 

  70. Mocini, D., Staibano, M., Mele, L., Giannantoni, P., Menichella, G., Colivicchi, F., et al. (2006). Autologous bone marrow mononuclear cell transplantation in patients undergoing coronary artery bypass grafting. American Heart Journal, 151(1), 192–197.

    Article  PubMed  Google Scholar 

  71. Hendrikx, M., Hensen, K., Clijsters, C., Jongen, H., Koninckx, R., Bijnens, E., et al. (2006). Recovery of regional but not global contractile function by the direct intramyocardial autologous bone marrow transplantation. Circulation, 114(1 suppl), I-101–I-107. doi:10.1161/circulationaha.105.000505.

    Article  Google Scholar 

  72. Ang, K.-L., Chin, D., Leyva, F., Foley, P., Kubal, C., Chalil, S., et al. (2008). Randomized, controlled trial of intramuscular or intracoronary injection of autologous bone marrow cells into scarred myocardium during CABG versus CABG alone. Nature Clinical Practice. Cardiovascular Medicine, 5(10), 663–670.

    Article  PubMed  Google Scholar 

  73. Yerebakan, C., Kaminski, A., Westphal, B., Donndorf, P., Glass, A., Liebold, A., et al. (2011). Impact of preoperative left ventricular function and time from infarction on the long-term benefits after intramyocardial CD133+ bone marrow stem cell transplant. The Journal of Thoracic and Cardiovascular Surgery, 142(6), 1530.e3–1539.e3.

    Article  Google Scholar 

  74. Perin, E. C., Dohmann, H. F. R., Borojevic, R., Silva, S. A., Sousa, A. L. S., Silva, G. V., et al. (2004). Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation, 110(11 suppl 1), II-213–II-218. doi:10.1161/01.cir.0000138398.77550.62.

    Article  Google Scholar 

  75. Beeres, S. L. M. A., Bax, J. J., Kaandorp, T. A. M., Zeppenfeld, K., Lamb, H. J., Dibbets-Schneider, P., et al. (2006). Usefulness of intramyocardial injection of autologous bone marrow-derived mononuclear cells in patients with severe angina pectoris and stress-induced myocardial ischemia. The American Journal of Cardiology, 97(9), 1326–1331.

    Article  PubMed  Google Scholar 

  76. Fuchs, S., Kornowski, R., Weisz, G., Satler, L. F., Smits, P. C., Okubagzi, P., et al. (2006). Safety and feasibility of transendocardial autologous bone marrow cell transplantation in patients with advanced heart disease. The American Journal of Cardiology, 97(6), 823–829.

    Article  PubMed  Google Scholar 

  77. Dib, N., Dinsmore, J., Lababidi, Z., White, B., Moravec, S., Campbell, A., et al. (2009). One-year follow-up of feasibility and safety of the first us, randomized, controlled study using 3-dimensional guided catheter-based delivery of autologous skeletal myoblasts for ischemic cardiomyopathy (CAuSMIC Study). JACC. Cardiovascular Interventions, 2(1), 9–16. doi:10.1016/j.jcin.2008.11.003.

    Article  PubMed  Google Scholar 

  78. Williams, A. R., Trachtenberg, B., Velazquez, D. L., McNiece, I., Altman, P., Rouy, D., et al. (2011). Intramyocardial stem cell injection in patients with ischemic cardiomyopathy/novelty and significance. Circulation Research, 108(7), 792–796. doi:10.1161/circresaha.111.242610.

    Article  PubMed  CAS  Google Scholar 

  79. Perin, E. C., Silva, G. V., Henry, T. D., Cabreira-Hansen, M. G., Moore, W. H., Coulter, S. A., et al. (2011). A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF). American Heart Journal, 161(6), 1078.e3–1087.e3.

    Article  Google Scholar 

  80. Povsic, T. J., O’Connor, C. M., Henry, T., Taussig, A., Kereiakes, D. J., Fortuin, F. D., et al. (2011). A double-blind, randomized, controlled, multicenter study to assess the safety and cardiovascular effects of skeletal myoblast implantation by catheter delivery in patients with chronic heart failure after myocardial infarction. American Heart Journal, 162(4), 654.e1–662.e1.

    Article  Google Scholar 

  81. Duckers, H. J., Houtgraaf, J., Hehrlein, C., Schofer, J., Waltenberger, J., Gershlick, A., et al. (2011). Final results of a phase IIa, randomised, open-label trial to evaluate the percutaneous intramyocardial transplantation of autologous skeletal myoblasts in congestive heart failure patients: the SEISMIC trial. EuroIntervention, 6(7), 805–812. doi:10.4244/eijv6i7a139.

    Article  PubMed  Google Scholar 

  82. Strauer, B. E., Brehm, M., Zeus, T., Kostering, M., Hernandez, A., Sorg, R. V., et al. (2002). Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation, 106(15), 1913–1918.

    Article  PubMed  Google Scholar 

  83. Schachinger, V., Assmus, B., Britten, M. B., Honold, J., Lehmann, R., Teupe, C., et al. (2004). Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. Journal of the American College of Cardiology, 44(8), 1690–1699.

    Article  PubMed  Google Scholar 

  84. Chen, S. L., Fang, W. W., Ye, F., Liu, Y. H., Qian, J., Shan, S. J., et al. (2004). Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. The American Journal of Cardiology, 94(1), 92–95.

    Article  PubMed  Google Scholar 

  85. Wollert, K. C., Meyer, G. P., Lotz, J., Ringes-Lichtenberg, S., Lippolt, P., Breidenbach, C., et al. (2004). Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet, 364(9429), 141–148.

    Article  PubMed  Google Scholar 

  86. Ruan, W., Pan, C. Z., Huang, G. Q., Li, Y. L., Ge, J. B., & Shu, X. H. (2005). Assessment of left ventricular segmental function after autologous bone marrow stem cells transplantation in patients with acute myocardial infarction by tissue tracking and strain imaging. Chinese Medical Journal, 118(14), 1175–1181.

    PubMed  Google Scholar 

  87. Strauer, B. E., Brehm, M., Zeus, T., Bartsch, T., Schannwell, C., Antke, C., et al. (2005). Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study. Journal of the American College of Cardiology, 46(9), 1651–1658.

    Article  PubMed  Google Scholar 

  88. Ge, J., Li, Y., Qian, J., Shi, J., Wang, Q., Niu, Y., et al. (2006). Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI). Heart, 92(12), 1764–1767.

    Article  PubMed  CAS  Google Scholar 

  89. Janssens, S., Dubois, C., Bogaert, J., Theunissen, K., Deroose, C., Desmet, W., et al. (2006). Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. The Lancet, 367(9505), 113–121.

    Article  Google Scholar 

  90. Lunde, K., Solheim, S., Aakhus, S., Arnesen, H., Abdelnoor, M., Egeland, T., et al. (2006). Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. The New England Journal of Medicine, 355(12), 1199–1209.

    Article  PubMed  CAS  Google Scholar 

  91. Assmus, B., Honold, J., Schachinger, V., Britten, M. B., Fischer-Rasokat, U., Lehmann, R., et al. (2006). Transcoronary transplantation of progenitor cells after myocardial infarction. The New England Journal of Medicine, 355(12), 1222–1232. doi:10.1056/NEJMoa051779.

    Article  PubMed  CAS  Google Scholar 

  92. Penicka, M., Horak, J., Kobylka, P., Pytlik, R., Kozak, T., Belohlavek, O., et al. (2007). Intracoronary injection of autologous bone marrow-derived mononuclear cells in patients with large anterior acute myocardial infarction: a prematurely terminated randomized study. Journal of the American College of Cardiology, 49(24), 2373–2374.

    Article  PubMed  Google Scholar 

  93. Li, Z. Q., Zhang, M., Jing, Y. Z., Zhang, W. W., Liu, Y., Cui, L. J., et al. (2007). The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI). International Journal of Cardiology, 115(1), 52–56.

    Article  PubMed  Google Scholar 

  94. Tatsumi, T., Ashihara, E., Yasui, T., Matsunaga, S., Kido, A., Sasada, Y., et al. (2007). Intracoronary transplantation of non-expanded peripheral blood-derived mononuclear cells promotes improvement of cardiac function in patients with acute myocardial infarction. Circulation Journal, 71(8), 1199–1207.

    Article  PubMed  Google Scholar 

  95. Huikuri, H. V., Kervinen, K., Niemela, M., Ylitalo, K., Saily, M., Koistinen, P., et al. (2008). Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction. European Heart Journal, 29(22), 2273–2737.

    Article  Google Scholar 

  96. Meluzin, J., Janousek, S., Mayer, J., Groch, L., Hornacek, I., Hlinomaz, O., et al. (2008). Three-, 6-, and 12-month results of autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction. International Journal of Cardiology, 128(2), 185–192.

    Article  PubMed  Google Scholar 

  97. Plewka, M., Krzeminska-Pakula, M., Peruga, J. Z., Lipiec, P., Kurpesa, M., Wierzbowska-Drabik, K., et al. (2009). The effects of intracoronary delivery of mononuclear bone marrow cells in patients with myocardial infarction: a two year follow-up results. Kardiologia Polska, 69(12), 1234–1240.

    Google Scholar 

  98. Cao, F., Sun, D., Li, C., Narsinh, K., Zhao, L., Li, X., et al. (2009). Long-term myocardial functional improvement after autologous bone marrow mononuclear cells transplantation in patients with ST-segment elevation myocardial infarction: 4 years follow-up. European Heart Journal, 30(16), 1986–1994.

    Article  PubMed  Google Scholar 

  99. Tendera, M., Wojakowski, W., Ruzyllo, W., Chojnowska, L., Kepka, C., Tracz, W., et al. (2009). Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial. European Heart Journal, 30(11), 1313–1321. doi:10.1093/eurheartj/ehp073.

    Article  PubMed  Google Scholar 

  100. Yousef, M., Schannwell, C. M., Kostering, M., Zeus, T., Brehm, M., & Strauer, B. E. (2009). The BALANCE Study: clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction. Journal of the American College of Cardiology, 53(24), 2262–2269. doi:10.1016/j.jacc.2009.02.051.

    Article  PubMed  Google Scholar 

  101. Grajek, S., Popiel, M., Gil, L., Breborowicz, P., Lesiak, M., Czepczynski, R., et al. (2010). Influence of bone marrow stem cells on left ventricle perfusion and ejection fraction in patients with acute myocardial infarction of anterior wall: randomized clinical trial: impact of bone marrow stem cell intracoronary infusion on improvement of microcirculation. European Heart Journal, 31(6), 691–702.

    Article  PubMed  Google Scholar 

  102. Strauer, B.-E., Yousef, M., & Schannwell, C. M. (2010). The acute and long-term effects of intracoronary stem cell transplantation in 191 patients with chronic heARt failure: the STAR-heart study. European Journal of Heart Failure, 12(7), 721–729. doi:10.1093/eurjhf/hfq095.

    Article  PubMed  Google Scholar 

  103. Suarez de Lezo, J., Herrera, C., Pan, M., Romero, M., Pavlovic, D., Segura, J., et al. (2007). Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function. Revista Española de Cardiología, 60(4), 357–365.

    Article  PubMed  Google Scholar 

  104. Piepoli, M. F., Vallisa, D., Arbasi, M., Cavanna, L., Cerri, L., Mori, M., et al. (2010). Bone marrow cell transplantation improves cardiac, autonomic, and functional indexes in acute anterior myocardial infarction patients (Cardiac Study). European Journal of Heart Failure, 12(2), 172–180. doi:10.1093/eurjhf/hfp183.

    Article  PubMed  Google Scholar 

  105. Wohrle, J., Merkle, N., Mailander, V., Nusser, T., Schauwecker, P., von Scheidt, F., et al. (2010). Results of intracoronary stem cell therapy after acute myocardial infarction. The American Journal of Cardiology, 105(6), 804–812.

    Article  PubMed  CAS  Google Scholar 

  106. Hirsch, A., Nijveldt, R., van der Vleuten, P. A., Tijssen, J. G. P., van der Giessen, W. J., Tio, R. A., et al. (2011). Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention: results of the randomized controlled HEBE trial. European Heart Journal, 32(14), 1736–1747. doi:10.1093/eurheartj/ehq449.

    Article  PubMed  Google Scholar 

  107. Roncalli, J., Mouquet, F., Piot, C., Trochu, J.-N., Le Corvoisier, P., Neuder, Y., et al. (2011). Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial. European Heart Journal, 32(14), 1748–1757. doi:10.1093/eurheartj/ehq455.

    Article  PubMed  Google Scholar 

  108. 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 myocardial infarction on left ventricular function. JAMA: The Journal of the American Medical Association, 306(19), 2110–2119. doi:10.1001/jama.2011.1670.

    Article  CAS  Google Scholar 

  109. Quyyumi, A. A., Waller, E. K., Murrow, J., Esteves, F., Galt, J., Oshinski, J., et al. (2011). CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent. American Heart Journal, 161(1), 98–105.

    Article  PubMed  Google Scholar 

  110. Stamm et al. (2003). Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. doi:10.1016/S0140-6736(03)12110-1.

Download references

Acknowledgments

This work was supported by the Barts and the London National Institute of Health Research Cardiovascular Biomedical Research Unit, London, UK and Barts and The London Charity. NC was supported by a clinical research training fellowship from the British Heart Foundation, UK.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ken Suzuki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Campbell, N.G., Suzuki, K. Cell Delivery Routes for Stem Cell Therapy to the Heart: Current and Future Approaches. J. of Cardiovasc. Trans. Res. 5, 713–726 (2012). https://doi.org/10.1007/s12265-012-9378-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-012-9378-3

Keywords

Navigation