Another SCIPIO Phase I trial at the University of Louisville that analyzed results through cardiac magnetic resonance (CMR) found that at one year LVEF increased by 41.2 percent, global and regional LV function improved, post-AMI size decreased by 30 percent, and viable tissue increased.
Cardiosphere-derived SCs (CDCs) are clusters of core c-kit-positive SCs, differentiating cells, and outer MSCs that form from myocardial tissue under appropriate culture conditions. Studies importantly demonstrate that CDCs express connexin-43 and form gap junctions, which allows electrical coupling.
The 2012 CADUCEUS trial at Cedars-Sinai Heart Institute found via CMR that autolo-gous endomyocardial-CDCs 1.5 to three months post-AMI resulted in reduction of post-AMI size and an increase in both viable cardiac mass and regional contractility. Although this trial did not demonstrate significant changes in LVEF, recent studies suggest the importance of SC therapies would be missed if EF were the sole endpoint, as EF is dependent upon non-cardiac factors, such as the neurohormonal state.
Measures of LV remodeling, such as decrease in chamber volume, sphericity index, and reduction of post-AMI size prove more clinically meaningful to elucidate SC treatment efficacy.
Future Directions
Several trials have tested optimal techniques of SC administration. Some demonstrate that intravenous administration leads to SC-entrapment in the liver and lungs. Intracoronary infusion is the most frequently used technique; however, it is associated with only 1–3 percent myocardial retention. Direct intramyocardial injection of SCs has been shown to result in higher myocardial cell retention without compromising coronary flow. However, preclinical and clinical studies suggest that more than just cells are necessary to mend a diseased heart—the framework to support cells is also crucial. Without reestablishment of adequate cardiac vascularization and extracellular matrix, SCs are unlikely to survive. Future clinical trials plan to identify optimal SCs that permit treatment without immune suppression, optimal timing for chemoattraction of SC to damaged cardiac tissue, and optimal propagation in the myocardium.
Krishna S. Vyas
Tara Shrout
University of Kentucky College of Medicine
See Also: Heart: Cell Types Composing the Tissue; Heart: Current Research on Isolation or Production of Therapeutic Cells; Heart: Development and Regeneration Potential; Heart: Existing or Potential Regenerative Medicine Strategies; Heart: Major Pathologies; Heart: Stem and Progenitor Cells in Adults; Heart: Tissue Function; Heart Disease.
Further Readings
Beltrami, A. P., L. Barlucchi, D. Torella, M. Baker, et al. “Adult Cardiac Stem Cells Are Multipotent and Support Myocardial Regeneration.” Cell, v.114/6 (2003).
Bolli, R., A. R. Chugh, D. D’Amario, J. H. Loughran, et al. “Cardiac Stem Cells in Patients With Ischaemic Cardiomyopathy (SCIPIO): Initial Results of a Randomised Phase 1 Trial.” Lancet, v.26/378 (2011).
Chen, S. L., W. W. Fang, F. Ye, Y. H. Liu, et al. “Effect on Left Ventricular Function of Intracoronary Transplantation of Autologous Bone Marrow Mesenchymal Stem Cell in Patients With Acute Myocardial Infarction.” American Journal of Cardiology, v.94/1 (2004).
Chugh, A.R., G. M. Beache, J. H. Loughran, N. Mewton, et al. “Administration of Cardiac Stem Cells in Patients With Ischemic Cardiomyopathy: The SCIPIO Trial: Surgical Aspects and Interim Analysis of Myocardial Function and Viability by Magnetic Resonance.” Circulation, v.126/11suppl1 (2012).
Duckers, H.J., J. Houtgraaf, C. Hehrlein, J. Schofer, et al. “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, v.6.7 (2011).
Hare, J. M., J. H. Traverse, T., D. Henry, N. Dib, et al. “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, v.54/24 (2009).
Li, T. S., K. Cheng, K. Malliaras, R. R. Smith, et al. “Direct Comparison of Different Stem Cell Types and Subpopulations Reveals Superior Paracrine Potency and Myocardial Repair Efficacy With Cardiosphere-Derived Cells.” Journal of the American College of Cardiology, v.59/10 (2012).
Makkar, R. R., R. R. Smith, K. Cheng, K. Malliaras, et al. “Intracoronary Cardiosphere-Derived Cells for Heart Regeneration After Myocardial Infarction (CADUCEUS): A Prospective, Randomised Phase 1 Trial.” Lancet, v.379/9819 (2012).
Murry, C. E., M. H. Soonpaa, H. Reinecke, H. Nakajima, et al. “Haematopoietic Stem Cells Do Not Transdifferentiate Into Cardiac Myocytes in Myocardial Infarcts.” Nature, v.428/6983 (2004).
Povsic, T. J., C. M. O’Connor, T. Henry, A. Taussig, et al. “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, v.162/4 (2011).
Ranganath, S. H., O. Levy, M. S. Inamdar, and J. M. Karp. “Harnessing the Mesenchymal Stem Cell Secretome for the Treatment of Cardiovascular Disease.” Cell Stem Cell, v.10/3 (2012).
“Stem Cells and Diseases.” Stem Cell Information. National Institutes of Health, U.S. Department of Health and Human Services (2014). http://stemcells.nih.gov/info/pages/health.aspx (Accessed April 2014).
Takahashi, K. and S. Yamanaka. “Induction of Pluripotent Stem Cells From Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors.” Cell, v.126/4 (2006).
Takashima, S., D. Tempel, and H. J. Duckers. “Current Outlook of Cardiac Stem Cell Therapy Towards a Clinical Application.” Heart, v.99/23 (2013).
Telukuntla, K. S., V. Y. Suncion, I. H. Schulman, and J. M. Hare. “The Advancing Field of Cell-Based Therapy: Insights and Lessons From Clinical Trials.” Journal of the American Heart Association, v.2/5 (2013).
Terrovitis, J. V., R. R. Smith, and E. Marbán. “Assessment and Optimization of Cell Engraftment After Transplantation Into the Heart.” Circulation Research, v.106 (2010).
Williams, A. R. and J. M. Hare. “Mesenchymal Stem Cells: Biology, Pathophysiology, Translational Findings, and Therapeutic Implications for Cardiac Disease.” Circulation Research, v.109/8 (2011).
Williams, A. R., B. Trachtenberg, D. L. Velazquez, I. McNiece, et al. “Intramyocardial Stem Cell Injection in Patients With Ischemic Cardiomyopathy: Functional Recovery and Reverse Remodeling.” Circulation Research, v.108/7 (2011).
Xu, R., S. Ding, Y. Zhao, J. Pu, and B. He. “Autologous Transplantation of Bone Marrow/Blood-Derived Cells for Chronic Ischemic Heart Disease: A Systematic Review and Meta-analysis.” Canadian Journal of Cardiology (January 23, 2014).
Clinical Trials, U.S.: Hematological Cancers
Clinical Trials, U.S.: Hematological Cancers
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Clinical Trials, U.S.: Hematological Cancers
Hematological cancers are malignancies affecting all blood cells, bone marrow, and the lymphatic system. The number of people suffering from such malignancies has helped to generate a great deal of interest