Umbilical Cord Blood and Bone Marrow for the Treatment of Cardiac Injury

Cardiac injury

Coronary heart disease (heart attack and angina) is the single leading cause of death in the United States and its prevalence is projected to double in the next half century. NSCI has focused on identifying stem cells in BM, UCB and MPB for the treatment of cardiac injury.

Cell transplantation is an increasingly attractive option for replacing damaged heart tissue or in other ways enhancing heart function following injury. Several cell types derived from adult BM have been investigated. Stem cell populations derived from Mouse BM have been demonstrated to engraft and improve function in mouse and rat infarct models [4-6]. Most promisingly, there have been some preliminary studies that demonstrated the ability of UCB stem cells to develop into heart muscle cells [7,8]. Since heart disease is typically the result of atherosclerotic disease of the blood vessels that supply the heart muscle, cellular therapies must also contend with reestablishment of an adequate blood supply. At least one study has suggested that UCB derived cells might be useful for engineering of vascular grafts [9]. In fact, initial reports of an improvement in heart function in animal models of myocardial infarction with BM-derived cells has already led to a number of human clinical trials [10,11].  Trials have differed in the specific progenitor cell type used, method of delivery, and type of patient treated.  Although the aim of these studies has primarily been to establish safety, they have almost uniformly also shown improved cardiac function [12-22]. 

Although potentially safer, autologous (the patient’s own) BM has a limitation in the case of acute heart injury when the patient has not banked stem cells in anticipation of injury. There is a time lag after heart attack between harvesting of the BM and preparation for readministration to the patient. The use of stem cells from banked UCB could speed up the process by as much as 2 days to over one week. With a disease process as acute as heart attack, time is critically important to heart function outcome. 

NSCI has developed safe and effective techniques to isolate stem cells from BM, UCB and MPB and is evaluating these cells in animal models of cardiac injury.

4. Davani, S., et al., Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a rat cellular cardiomyoplasty model. Circulation, 2003. 108 Suppl 1: p. II253-8.

5. Kudo, M., et al., Implantation of bone marrow stem cells reduces the infarction and fibrosis in ischemic mouse heart. J Mol Cell Cardiol, 2003. 35(9): p. 1113-9.

6. Tang, Y.L., et al., Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul Pept, 2004. 117(1): p. 3-10.

7. Cheng, F., et al., Induced differentiation of human cord blood mesenchymal stem/progenitor cells into cardiomyocyte-like cells in vitro. J Huazhong Univ Sci Technolog Med Sci, 2003. 23(2): p. 154-7.

8. Vanelli, P., et al., Cardiac precursors in human bone marrow and cord blood: in vitro cell cardiogenesis. Ital Heart J, 2004. 5(5): p. 384-8.

9. Schmidt, D., et al., Umbilical cord blood derived endothelial progenitor cells for tissue engineering of vascular grafts. Ann Thorac Surg, 2004. 78(6): p. 2094-8.

10. Mathur, A. and J.F. Martin, Stem cells and repair of the heart. Lancet, 2004. 364(9429): p. 183-92.

11. Bick-Forrester, J., et al., Partial restoration of myocardial function and perfusion by cell therapy following myocardial infarction. Curr Opin Cardiol, 2004. 19(6): p. 631-7.

12. Stamm, C., et al., Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet, 2003. 361(9351): p. 45-6.

13. Perin, E.C., et al., Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation, 2003. 107(18): p. 2294-302.

14. Fuchs, S., et al., Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol, 2003. 41(10): p. 1721-4.

15. Galinanes, M., et al., Autotransplantation of unmanipulated bone marrow into scarred myocardium is safe and enhances cardiac function in humans. Cell Transplant, 2004. 13(1): p. 7-13.

16. Strauer, B.E., et al., Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation, 2002. 106(15): p. 1913-8.

17. Assmus, B., et al., Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation, 2002. 106(24): p. 3009-17.

18. Dobert, N., et al., Transplantation of progenitor cells after reperfused acute myocardial infarction: evaluation of perfusion and myocardial viability with FDG-PET and thallium SPECT. Eur J Nucl Med Mol Imaging, 2004. 31(8): p. 1146-51.

19. Wollert, K.C., et al., Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet, 2004. 364(9429): p. 141-8.

20. Belenkov Iu, N., et al., [Mobilization of bone marrow stem cells in the management of patients with heart failure. Protocol and first results of ROT FRONT trial]. Kardiologiia, 2003. 43(3): p. 7-12.

21. Kang, H.J., et al., Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet, 2004. 363(9411): p. 751-6.

22. Kuethe, F., et al., [Mobilization of stem cells by granulocyte colony-stimulating factor for the regeneration of myocardial tissue after myocardial infarction]. Dtsch Med Wochenschr, 2004. 129(9): p. 424-8.