Fetal stem cells in combined treatment of chronic heart failure and their effect on morphofunctional parameters of the left ventricle myocardium

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Cell and Organ Transplantology. 2014; 2(1):20-24.
DOI: 10.22494/COT.V2I1.35

Fetal stem cells in combined treatment of chronic heart failure and their effect on morphofunctional parameters of the left ventricle myocardium

Klunnyk M. O., Sych N. S., Matiyaschuk I. G., Ivankova O. V., Demchuk M. P., Skalozub M. V., Sinelnyk A. A.
Cell Therapy Center EmCell, Kyiv, Ukraine

Abstract
Fetal stem cells treatment (FSCT) is assumed to be a new direction in a combined therapy for the patients with the severe chronic heart failure (CHF).
Material and methods. 20 patients (average age of 50.1 ± 1.1 yrs.) with CHF functional class III-IV (FC) undergoing the transplantation of the cryopreserved cells of the fetal liver and heart obtained from 5-8 weeks gestation embryos were examined. The control group (CG) of 20 patients was compared by gender and age with the main group (MG).
Results. Within 6 months after FSC therapy CHF patients reported a significant improvement of the contractile activity of the left ventricle (LV) heart muscle in echocardiography (EchoCG) findings (left ventricular ejection fraction (LVEF) increased by 20.9 % being 2-fold higher than in patients without FSCT, p<0.05) and in features of LV remodeling (left ventricle end diastolic volume (LV EDV) decreased by 20.5 %, p < 0.05). Serum NT-proBNP significantly raised within 1 month after FSCT by 33.8 %, 50 % and 65.1 % in 1, 3 and 6 months respectively (p<0.001) and was significantly lower after a month of treatment compared with CG (р<0.05).
As a result of general condition improvement in CHF patients significant elevation in 6 minute walking distance (6MWD) test was observed and the distance walked increased 7.3-fold (p<0.001), 10.3-fold (p<0.001) and 12.5-fold (p<0.001) vs. the baseline in 1, 3 and 6 months, respectively, which was generally 2-fold higher than in patients of the CG. DASI score increased by 54.6 %, after 3 months — by 63.2 %, after 6 months — by 66.4 %, which is significantly higher than the baseline (p<0.05 vs. baseline).
Conclusion. It has been proven that combined treatment of CHF patients using FSCs along with the standard therapy increases the LV myocardial contractility, lowering the blood serum NT-proBNP level and results in overall life quality improvement among the patients.

Key words: heart failure, fetal stem cells, left ventricle function remodeling

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1. Acanfora D, Trojano L, Iannuzzi GL, et al. The brain in congestive heart failure ArchGerontolGeriatr. 1996; 23:247-56.
https://doi.org/10.1016/S0167-4943(96)00733-9
2. Asger A, Møller JM, Daugaard PC, et al. Effectsof phosphodiesterase-5 inhibition by sildenafil in the pressure overloaded right heart. Eur J Heart Fail. 2008; 10:1153-7.
3. Enright PL, Sherill DL. Reference equations for the six-minute walk in healthy adults. Am J Respir Crit Care Med. 1998; 158:1384-7.
https://doi.org/10.1164/ajrccm.158.5.9710086
PMid:9817683
4. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981; 292(5819):154-6.
https://doi.org/10.1038/292154a0
5. Feigenbaum H. Echocardiography. 5th Ed. Philadelphia: Lea&Febiger. 1994; 675 p.
6. Georgiadis D, Sievert M, Cencetti S, et al. Cerebrovascular reactivity is impaired in patients with cardiac failure. Eur Heart J. 2000; 21:407-13.
https://doi.org/10.1053/euhj.1999.1742
PMid:10666355
7. Kamihata H, Matsubara H, Nishiue T, et al. Implantation of bone marrow mononuclear cells in to ischemic myocardium enhances collateral perfusion and regional function via side upply of angioblasts, angiogenic ligands, andcytokines. Circulation. 2001; 104:1046-52.
https://doi.org/10.1161/hc3501.093817
PMid:11524400
8. Lainchbury JG, Troughton RW, Frampton CM, et al. NTproBNP-guided drug treatment for chronic heart failure: design and methods in the “BATTLESCARRED” trial. Eur J Heart Fail. 2006; 8:532-8.
https://doi.org/10.1016/j.ejheart.2006.04.004
PMid:16829189
9. LeBlanc K, Ringdén O. Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005; 11:321-34.
https://doi.org/10.1016/j.bbmt.2005.01.005
PMid:15846285
10. Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest. 1999; 103:697-705.
https://doi.org/10.1172/JCI5298
PMid:10074487 PMCid:PMC408125
11. Menasche P, Hagege A, Scorsin M, et al. Myoblast transplantation for heart failure. Lancet. 2001; 357:279-80.
https://doi.org/10.1016/S0140-6736(00)03617-5
12. Nichols WW, O’Rourke MF. Aging, high blood pressure and disease in humans. In: Arnold E, ed. McDonald’s Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles. 3rd ed. London/Melbourne/Auckland: Lea and Febiger. 1990: 398-420.
13. Ohno N, Fedak PW, Weisel RD, Komeda M, Mickle DA, Li RK. Cell transplantation in non-ischemic dilated cardiomyopathy. A novel biological approach for ventricular restoration. Jpn J Thorac Cardiovasc Surg. 2002; 50:457-60.
https://doi.org/10.1007/BF02919635
PMid:12478864
14. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001; 410:701-5.
https://doi.org/10.1038/35070587
PMid:11287958
15. Ostroumov EN, Yermolenko AE, Gureev SV, et al. Right ventricle ejection fraction as myocardium revascularisation efficiency marker in ischemic heart disease with congestive circulatory failure. Cardiology. 1996; 4:57-61.
16. Panteghini M. (2004) Recommendations on use of biochemical markers in acute coronary syndrome: IFCC proposals. eJIFCC. 14(2). Available: http://www.ifcc.org/ifcc-communications-publications-division-%28cpd%29/ifcc-publications/ejifcc-%28journal%29/e-journal-volumes/vol-14-n%C2%B0-2/recommendations-on-use-of-biochemical-markers-in-acute-coronary-syndrome-ifcc-proposals.
17. Petrenko AY, Khunov YA, Ivanov YN. Stem cells. Properties and clinical perspectives. Luhansk, Ukraine: Press Express. 2001:224-239.
18. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchimal stem cells. Science. 1999; 284:143-7.
https://doi.org/10.1126/science.284.5411.143
PMid:10102814
19. Potapov IV, Bashkina LV, Zaydenov VA, et al. Effect of embryonic cardiomyocytes and mesenchymal cell transplantation on contractile function of the heart in experimental myocardial infarction. Bull Transplantol Artif Organ. 2002; 3:88-9.
20. Robbins MA, O’Connell JB. Economic impact of heart failure in management of end-stage heart disease. In: Rose E.A., Stevenson L.W. Management of end-stage heart disease. Philadelphia: Lippincott-Raven, 1998:3–11.
21. Sakakibara Y, Tambara K, Lu F, et al. Combined procedure of surgical repair and cell transplantation for left ventricular aneurysm: An experimental study. Circulation. 2002; 106(I):193-7.
22. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Nat Med. 2001; 7:430-6.
https://doi.org/10.1038/86498
PMid:11283669
23. Taupin P. Stem cells and regenerative medicine. In: Pharmacology and therapy. Vol. III. NewYork: Nova Science Publishers. 2008; 135 p.
24. Tomita S, Li RK, Weisel RD, et al. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation. 1999; 100(II):247-56.
https://doi.org/10.1161/01.cir.100.suppl_2.ii-247
25. Tomita S, Mickle DAG, Weisel RD, et al. Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J Thorac Cardiovasc Surg. 2002; 123:1132-40.
https://doi.org/10.1067/mtc.2002.120716
PMid:12063460
26. Wang J-S, Shum-Tim D, Galipeau J, Chedrawy E, Eliopoulos N, Chiu RC. Marrow stromal cells for cellular cardiomyoplasty: Feasibility and potential clinical advantages. J Thorac Cardiovasc Surg. 2000; 120:999-1006.
https://doi.org/10.1067/mtc.2000.110250
PMid:11044327
27. Wang J-S, Shum-Tim D, Chedrawy E, Chiu RC The coronary delivery of marrow stromal cells for myocardial regeneration: Pathophysiologic and therapeutic implications. J Thorac Cardiovasc Surg. 2001; 122:699-705.
https://doi.org/10.1067/mtc.2001.116317
PMid:11581601

Klunnyk MO, Sych NS, Matiyaschuk IG, Ivankova OV, Demchuk MP, Skalozub MV, Sinelnyk AA. Fetal stem cells in combined treatment of chronic heart failure and their effect on morphofunctional parameters of the left ventricle myocardium. Cell and Organ Transplantology. 2014; 2(1):20-24. doi: 10.22494/COT.V2I1.35

 

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