Статья
Возможности использования стволовых клеток для лечения больных с ишемической болезнью сердца. Часть II. Мононуклеарная фракция клеток костного мозга
Клеточная кардиомиопластика — относительно новый подход к восстановлению функции сердца, поврежденного в результате инфаркта миокарда (ИМ). Экспериментальные и первые клинические исследования по трансплантации стволовых клеток (СК) больным острым ИМ и сердечной недостаточностью показали возможность улучшения перфузии и сократимости миокарда за счет ангиогенеза, уменьшения апоптоза кардиомиоцитов (КМЦ) и ремоделирования левого желудочка. Однако, несмотря на многообещающие результаты, остается много препятствий для того, чтобы СК стали использоваться для лечения пациентов с сердечно-сосудистыми заболеваниями. Многие фундаментальные вопросы еще только предстоит выяснить в будущих исследованиях: механизмы хоуминга, дифференцировки и приживления трансплантированных СК, механизмы влияния трансплантированных клеток на сердечную функцию и др. Остается предметом дискуссии наиболее предпочтительный источник СК для трансплантации в клинике, способ доставки клеток в миокард, время проведения кардиомиопластики, количество клеток в трансплантате и способы его подготовки. Во второй части обзора представлена характеристика мононуклеарной фракции клеток костного мозга, которая наиболее широко используется в клинических исследованиях, изучающих влияние этого типа клеток на функциональное состояние поврежденного миокарда. Обсуждены некоторые проблемы и вопросы безопасности клеточной терапии сердца.
1. Assmus B, Honold J, Schächinger V, et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 2006; 355: 1222-32.
2. Lunde K, Solheim S, Aakhus S, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006; 355: 1199-209.
3. Janssens S, Dubois C, Bogaert J, et al. Autologous bone marrowderived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 2006; 367: 113-21.
4. Meyer GP, Wollert KC, Lotz J, et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months’ follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation 2006; 113: 1287-94.
5. Strauer B, Brehm M, Zeus T, et al. Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study. JACC 2005; 46: 1651.
6. Tse H, Kwong Y, Chan J, et al. Angiogenesis in ischemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 2003; 361: 47.
7. Fuchs S, Satler L, Kornowski R, et al. Catheter -based autologous bone marrow myocardiul injection in no-option patients with advanced coronary artery disease: a feasibility study. JACC 2003; 41: 1721.
8. Perin E, Dohman H, Borojevic R, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 2003; 107: 2294.
9. Haider H. Bone marrow cells for cardiac regeneration and repair: curent status and issues. Expert Rev Cardiovasc Ther 2006; 4: 557-68.
10. Sakai T, Li RK, Weisel RD et al. Fetal cell transplantation: a comparison of three cell types. J Thorac Cardiovasc Surg 1999; 118: 715-25.
11. Hutcheson KA, Atkins BZ, Hopkins MB, et al. Comparing cell types for cellular cardiomyoplasty: analysis of improved diastolic properties with autologous skeletal myoblasts and fibroblasts. Circ 1999; 100 (suppl I): I-118.
12. Agbulut O, Vandervelde S, Attar NA, et al. Comparison of human skeletal myoblasts and bone marrow-derived CD133+ progenitors for the repair of infarcted myocardium. JACC 2004; 44: 458-63.
13. Timmermans F, De Sutter J, Gillebert T. Stem cells for the heart? are we there yet? Cardiology 2003, 100; 4: 176-85.
14. Beltrami CA, Finato N, Rocco M, et al. Structural basis of endstage failure in ischemic cardiomyopathy in humans. Circulation 1994; 89: 151-63.
15. Penicka M, Widimsky P, Kobylka P, et al. Early tissue distribution of bone marrow mononuclear cells after transcoronary transplantation in a patient with acute myocardial infarction. Circulation 2005; 112: e63-5.
16. Geng YJ. Molecular mechanisms for cardiovascular stem cell apoptosis and growth in the hearts with atherosclerotic coronary disease and ischemic heart failure. Ann N Y Acad Sci 2003; 1010: 687-97.
17. Nygren JM, Jovinge S, Breitbach M, et al. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 2004; 10: 494-501.
18. Chien KR. Stem cells: lost in translation. Nature 2004; 428: 607-8.
19. Fuchs S, Baffour R, Zhou YF, et al. Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. JACC 2001; 37: 1726-32.
20. Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001; 7:430-6.
21. Thum T, Bauersachs J, Poole-Wilson P, et al. The dying stem cell hypothesis: immune modulation as a novel mechanism for progenitor cell therapy in cardiac muscle. JACC 2005; 46: 1799-802.
22. Nagaya N, Fugii T, Iwase T, et al. Intravenous administration of mesenchimal stem cells improves cardiac function in rats with acute myocardium infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol 2004; 287: 2670-6.
23. Siepe M, Heilmann C, von Samson P, et al. Stem cell research and cell transplantation for myocardial infatction. Eur J Cardiothorac Surg 2005; 28: 318-24.
24. Ghodsizad A, Klein HM, Borowski A, et al. Intraoperative isolation and processing of BM-derived stem cells. Cytotherapy 2004; 6(5): 523-6.
25. Lee M, Makka R. Stem-cell transplantation in myocardial infarction: a status report. Ann Intern Med 2004; 140(9): 729-37.
26. Perin E, Silva G, Sarmento-Leite R, et al. Assessing myocardial viability and infarct transmurality with left ventricular electromechanical mapping in patients with stable coronary artery disease: validation by delayed-enchncement magnetic resonance imaging. Circulation 2002; 107: 957-61.
27. Hou D, Youssef EA, Brinton T, et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 2005; 112(Suppl.I): 150-6.
28. Rochitte C, Lima J, Bluemke D, et al. Magnitude and time course of microvascular obstruction and tissue injury after acute myocardial infarction. Circulation 1998; 98: 1006-14.
29. Pannitteri G, Petrucci E, Testa U. Coordinate release of angiogenic growth factors after acute myocardial infarction: evidence of a two-wave production. J Cardiovasc Med 2006; 7: 872-9.
30. Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res (2001) 89: E1-7.
31. Baddorf C, Brandes R, Popp R, et al. Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocites. Circulation 2003; 107: 1024-32.
32. Heng B, Haider H, Sim E, et al. Strategies for directing the differentiation of stem cells inti the cardiomyogenetic lineage in vitro. Cardiovasc Res 2004; 62: 34-42.
33. Rafii S, lyden D. Therapeutic stem and progenitor cell transplantation for organ organ vascu-larization. Nat Med 2003; 9: 712.
34. Vulliet PR, Greeley M, Halloran SM, et al. Intracoronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 2004; 363: 783-4.
35. Kang HJ, Lee HY, Na SH, et al. 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 2006; 114: I145-51.
36. Breitbach M, Bostani T, Roell W, et al. Potential risks of bone marrow cell transplantation into infarcted hearts. BLOOD 2007; 110; 1362.
37. Michael J, Lipinski, Giuseppe G, et al. Impact of Intracoronary Cell Therapy on Left Ventricular Function in the Setting of Acute Myocardial Infarction: A Collaborative Systematic Review and Meta-Analysis of Controlled Clinical Trials. JACC 2007; 50: 1761-7.
38. Ahmed Abdel-Latif; Roberto Bolli; Imad M, et al. Adult Bone Marrow-Derived Cells for Cardiac Repair: A Systematic Review and Meta-analysis. Arch Intern Med 2007; 167: 989-97.
39. Yousef M, Schannwell CM, Kostering M, et al. The BALANCE study. Clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction. JACC 2009; 53: 2262-9.
40. Forrester JS, Makkar RR, Marban E. Long-term outcome of stem cell therapy for acute myocardial infarction. JACC 2009; 53: 2270-2.
41. Guolong Yu, Borlongan C, Stahl Ch, et al. Transplantation of human umbilical cord blood cells for the repair of myocardial infarction. Med Sci Monit 2008; 14(10): 163-72.
42. Scheuber RJ, Zorn H, Silber RE, et al: Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting. JACC 2003; 42: 2073-80.
43. Eizawa T, Ikeda U, Murakami Y, et al. Decrease in circulating endothelial progenitor cells in patients with stable coronary artery disease. Heart 2004; 90: 685-6.
44. Newman MB, Davis CD, Borlongan CV, et al. Transplantation of human umbilical cord blood cells in the repair of CNS diseases. Expert Opin Biol Ther 2004; 4: 121-30.
45. Broxmeyer HE, Srour EF, Hangoc G, et al. High-efficiency recovery of functional hematopoetic progenitor and stem cells from human cord blood cryopreserved for 15 years. Proc Nat Acad Sci USA 2003; 100: 645-50.
46. Wagner JE, Kernan NA, Steinbuch M, et al. Allogenic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease. Lancet 1995; 346: 214-9.
47. Henning RJ, Abu-Ali H, Balis JU, et al. Human umbilical cord blood mononuclear cells for the treatment of acute myocardial infarction. Cell Tranplant 2005; 13: 729-39.
48. Hirata Y, Sata M, Motomura, et al. Human umbilical cord blood cells improve cardiac function after myocardial infarction. Biochem Biophys Res Commun 2005; 327: 609-14.
49. Kim BO, Tian H, Prasongsukarn K, et al. Cell transplantation improves ventricular function after myocardial unfarction: a preclinical study of human unrestricted somatic stem cells in a porcine model. Circulation 2005; 112(9suppl): 196-204.
50. Ma N, Ladilov Y, Kaminski A, et al. Umbilical cord blood cells transplantation for myocardial regeneration. Transplant Proc 2006; 38: 771-3.
51. Hu CH, Wu GF, Wang XQ, et al. Therapeutic potencial of human umbilical cord derived stem cells in a rat myocardial infarction model. Ann Thorac Surg 2007; 83: 1492-8.
52. Yamada Y, Yokoyama S, Fukuda N, et al. A novel approach for myocardial regeneration with educated cord blood cells cocultured with cells from brown adipose tissue. Biochem Biophys Res Comun 2007; 353: 182-8.
53. Cortes-Morichetti M, Frati G, Schussler O, et al. Association between a cell-seeded collagen matrix and cellular cardiomyoplasty for myocardial support and regeneration. Tissue Eng 2007; 13: 2681-7.
54. Spyridonidis A., Zeiser R., Folio M. et al. Stem cell plasticity: the debate begins to clarify. Stem Cell Rev 2005; 1: 37-43.
55. Рябов В.В., Марков В.А., Попонина Ю.С. и др. Цитокины и аутологичные мононуклеарные клетки костного мозга в процессах восстановительной регенерации при инфаркте миокарда. Кардиоваск тер профил 2007; 5.
56. Руда М.Я., Староверов И.И., Жукова Н.С. и др. Опыт использования стволовых клеток в лечении больных острым инфарктом миокарда с низкой фракцией выброса. Кардиология 2009; 7-8: 19-24.
57. Ахмедов Ш.Д., Бабокин В.Е., Коркин Ю.Г. и др. Аутологичные стволовые клетки в лечении хронической сердечной недостаточности. Хирургические и моральные аспекты. “Стволовые клетки: законодательство, исследования и инновации. Международные перспективы сотрудничества” (тез. докл.) Москва 2007.
58. Акчурин Р.С., Рахмат-Заде Т.М., Скридлевская Е.А. и др. Аутологичные культивированные костномозговые стволовые клетки в хирургическом лечении хронической сердечной недостаточности. “Стволовые клетки: законодательство, исследования и инновации. Международные перспективы сотрудничества” (тез. докл.), Москва 2007.
59. Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004; 364: 141-8.
60. Schächinger V, Erbs S, Elsässer A, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 2006; 355: 1210-21.