Стволовые клетки сердца: факт или фантазия?
https://doi.org/10.15829/1560-4071-2019-11-84-90
Аннотация
Весной 2018г Гарвардская медицинская школа и Бригамская и женская больница сообщили об отзыве 31 статьи научной группы Пьеро Анверса, занимающихся более 15 лет исследованием стволовых клеток сердца, в связи с тем, что в этих статьях выявлены “сфальсифицированные и/или сфабрикованные данные”. Эта крайне неприятная история бросила тень на другие группы исследователей, работающих в области изучения регенеративных эффектов клеток, получаемых из миокарда, и способствовала появлению крайне скептического мнения о возможностях регенеративных технологий в кардиологии вообще и полного отрицания наличия в сердце какого-либо регенеративного потенциала. В данном обзоре представлен анализ истории работ группы Анверса и других работ, посвященных изучению механизмов регенеративных процессов в сердце, современный взгляд на механизмы регенеративного потенциала сердца и регенеративных эффектов прогениторных клеток, получаемых из миокарда, и перспективы развития клеточных технологий в кардиологии.
При поддержке: Работа поддержана грантом РНФ № 19-15-00384
Об авторе
Е. В. Парфенова
НМИЦ кардиологии Минздрава России; МГУ им. М.В. Ломоносова
Россия
Россия
Парфенова Елена Викторовна — руководитель лаборатории ангиогенеза, директор Института Экспериментальной Кардиологии, заместитель генерального директора по научной работе; профессор кафедры биохимии и молекулярной медицины, Факультет фундаментальной медицины.
Москва.
ResearcherID: B-9307-2014
Список литературы
1. Sylva M, van den Hoff MJ, Moorman AF. Development of the human heart. Am J Med Genet A. 2014 Jun;164A(6):1347-71. doi:10.1002/ajmg.a.35896.
2. Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003 Sep 19;114(6):763-76. doi:10.1016/s0092-8674(03)00687-1.
3. Urbanek K, Torella D, Sheikh F, et al. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure.Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8692-7. doi:10.1073/pnas.0500169102.
4. Barile L, Messina E, Giacomello A, et al. Endogenous cardiac stem cells. Prog Cardiovasc Dis. 2007 Jul-Aug;50(1):31-48. doi:10.1016/j.pcad.2007.03.005.
5. Bearzi C, Rota M, Hosoda T, et al. Human cardiac stem cells. Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14068-73. doi:10.1073/pnas.0706760104.
6. Urbanek K, Rota M, Cascapera S, et al. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival.Circ Res. 2005 Sep 30;97(7):663-73. doi: 10.1161/01.RES.0000183733.53101.11.
7. Linke A, Müller P, Nurzynska D, et al. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8966-71. DOI: 10.1073/pnas.0502678102.
8. Ellison GM, Torella D, Dellegrottaglie, S et al. Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart. J Am Coll Cardiol. 2011 Aug 23;58(9):977-86. doi:10.1016/j.jacc.2011.05.013.
9. Cai CL, Molkentin JD. The elusive progenitor cell in cardiac regeneration: slip slidin’ away. Circ Res. 2017;120:400-6. doi:10.1161/CIRCRESAHA.116.309710.
10. Dergilev K, Tsokolaeva Z, Makarevich P, et al. C-Kit Cardiac Progenitor Cell Based Cell Sheet Improves Vascularization and Attenuates Cardiac Remodeling following Myocardial Infarction in Rats. Biomed Res Int. 2018 Jun 25;2018:3536854. doi:10.1155/2018/3536854.
11. Zwetsloot PP, Végh AM, Jansen of Lorkeers SJ, et al. Cardiac Stem Cell Treatment in Myocardial Infarction: A Systematic Review and Meta-Analysis of Preclinical Studies.Circ Res. 2016 Apr 15;118(8):1223-32. doi:10.1161/CIRCRESAHA.115.307676.
12. Kajstura J, Urbanek K, Perl S, et al. Cardiomyogenesis in the adult human heart. Circ Res. 2010 Jul 23;107(2):305-15. doi: 10.1161/CIRCRESAHA.110.223024. Epub 2010 Jun 3. Retraction in: Circ Res. 2019 Feb 15;124(4):e22.
13. Kajstura J, Rota M, Cappetta D, et al. Cardiomyogenesis in the aging and failing human heart. Circulation. 2012 Oct 9;126(15):1869-81. Retracted. doi:10.1161/CIRCULATIONAHA.112.118380.
14. Bergmann O, Bhardwaj RD, Bernard S, et al. Evidence for cardiomyocyte renewal in humans. Science. 2009 Apr 3;324(5923):98-102. doi:10.1126/science.1164680.
15. Aquila I, Marino F, Cianflone E, et al. The use and abuse of Cre/Lox recombination to identify adult cardiomyocyte renewal rate and origin. Pharmacol Res. 2018 Jan;127:116-28. doi:10.1016/j.phrs.2017.06.012.
16. Leri A, Rota M, Pasqualini FS, et al. Origin of cardiomyocytes in the adult heart. Circ Res. 2015 Jan 2;116(1):150-66. doi:10.1161/CIRCRESAHA.116.303595.
17. Senyo SE, Steinhauser ML, Pizzimenti CL, et al. Mammalian heart renewal by pre-existing cardiomyocytes. Nature. 2013;493:433-6. doi:10.1038/nature11682.
18. van Berlo JH, Kanisicak O, Maillet M et al. c-kit+ cells minimally contribute cardiomyocytes to the heart. Nature. 2014;509:337-41. doi:10.1038/nature13309.
19. Sultana N, Zhang L, Yan J, et al. Resident c-kit(+) cells in the heart are not cardiac stem cells. Nat Commun. 2015;6:8701. doi:10.1038/ncomms9701.
20. Wang WE, Li L, Xia X, et al. Dedifferentiation, Proliferation, and Redifferentiation of Adult Mammalian Cardiomyocytes After Ischemic Injury. Circulation. 2017 Aug 29;136(9):834-48. doi:10.1161/CIRCULATIONAHA.116.024307.
21. Barile L, Milano G, Vassalli G. Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia. Stem Cell Investig. 2017;4:93. doi:10.21037/sci.2017.11.06.
22. Xiao J, Pan Y, Li XH, et al. Cardiac progenitor cell-derived exosomes prevent cardiomyocytes apoptosis through exosomal miR-21 by targeting PDCD4. Cell Death Dis. 2016 Jun 23;7(6):e2277. doi:10.1038/cddis.2016.181.
23. Ibrahim AG, Cheng K, Marbán E. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Reports. 2014 May 8;2(5):606-19. doi:10.1016/j.stemcr.2014.04.006.
24. Mol EA, Goumans MJ, Sluijter JPG. Cardiac Progenitor-Cell Derived Exosomes as Cell-Free Therapeutic for Cardiac Repair. Adv Exp Med Biol. 2017;998:207-19. doi:10.1007/978-981-10-4397-0_14.
25. Sahoo S, Losordo DW. Exosomes and cardiac repair after myocardial infarction. Circ Res. 2014 Jan 17;114(2):333-44. doi:10.1161/CIRCRESAHA.114.300639.
26. Keith MC, Bolli R. “String theory” of c-kit(pos) cardiac cells: a new paradigm regarding the nature of these cells that may reconcile apparently discrepant results. Circ Res. 2015 Mar 27;116(7):1216-30. doi:10.1161/CIRCRESAHA.116.305557.
27. Gambini E, Pompilio G, Biondi A, et al. C-kit+ cardiac progenitors exhibit mesenchymal markers and preferential cardiovascular commitment. Cardiovascular research. 2011;89:362-73. doi:10.1093/cvr/cvq292.
28. Blazquez-Martinez A, Chiesa M, Arnalich F, et al. C-kit identifies a subpopulation of mesenchymal stem cells in adipose tissue with higher telomerase expression and differentiation potential. Differentiation; research in biological diversity. 2014;87:147-60. doi:10.1016/j.diff.2014.02.007.
29. Smits AM, Dronkers E, Goumans MJ. The epicardium as a source of multipotent adult cardiac progenitor cells: Their origin, role and fate. Pharmacol Res. 2018 Jan;127:129-40. doi:10.1016/j.phrs.2017.07.020.
30. Zhou B, Honor LB, He H, et al. Adult mouse epicardium modulates myocardial injury by secreting paracrine factors. J Clin Invest. 2011;121:1894-904. doi:10.1172/JCI45529.
31. Bolli R, Chugh AR, D’Amario D, et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet. 2011;378:1847-57. Retracted. doi:10.1016/S0140-6736(11)61590-0.
32. Makkar RR, Smith RR, Cheng K, et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet. 2012;379:895-904.
33. Chakravarty T, Makkar RR, Ascheim DD, et al. ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR) Trial: Rationale and Design. Cell Transplant. 2017 Feb 16;26(2):205-14. doi:10.3727/096368916X692933.
34. Sanz-Ruiz R, Casado Plasencia A, Borlado LR, et al. Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction). Circ Res. 2017 Jun 23;121(1):71-80. doi:10.1161/CIRCRESAHA.117.310651.
35. Chugh AR, Beache GM, Loughran JH, et al. Administration of cardiac stem cells in patients with ischemic cardiomyopathy:the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viabilityby magnetic resonance. Circulation. 2012 Sep 11;126(11 Suppl 1):S54-64. doi:10.1161/CIRCULATIONAHA.112.092627.
36. Eschenhagen T, Bolli R, Braun T, et al. Cardiomyocyte Regeneration: A Consensus Statement. Circulation. 2017 Aug 15;136(7):680-6. doi:10.1161/CIRCULATIONAHA.117.029343.
37. Oskouei BN, Lamirault G, Joseph C, et al. Increased potency of cardiac stem cells compared with bone marrow mesenchymal stem cells in cardiac repair. Stem Cells Transl Med. 2012 Feb;1(2):116-24. doi:10.5966/sctm.2011-0015.
38. Li TS, Cheng K, Malliaras K, et al. Direct comparison of different stem cell types and subpopulations reveals superiorparacrine potency and myocardial repair efficacy with cardiosphere-derived cells. J Am Coll Cardiol. 2012 Mar 6;59(10):942-53. doi:10.1016/j.jacc.2011.11.029.
39. Bao L, Meng Q, Li Y, et al. C-Kit Positive Cardiac Stem Cells and Bone Marrow-Derived Mesenchymal Stem Cells Synergistically Enhance Angiogenesis and Improve Cardiac Function After Myocardial Infarction in a Paracrine Manne. J Card Fail. 2017 May;23(5):403-15. doi:10.1016/j.cardfail.2017.03.002.
40. Williams AR, Hatzistergos KE, Addicott B, et al. Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation. 2013 Jan 15;127(2):213-23. doi:10.1161/CIRCULATIONAHA.112.131110.
41. Aguado BA, Mulyasasmita W, Su J, et al. Improving viability of stem cells during syringe needle flow through the design of hydrogel cell carriers. Tissue Eng A. 2012;18:806-15. doi:10.1089/ten.TEA.2011.0391.
42. Fan Z, Xu Z, Niu H, et al. An Injectable Oxygen Release System to Augment Cell Survival and Promote CardiacRepair Following Myocardial Infarction. Sci Rep. 2018 Jan 22;8(1):1371. doi:10.1038/s41598-018-19906-w.
43. Madonna R, Van Laake LW, Botker HE, et al. ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure. Cardiovasc Res. 2019 Mar 1;115(3):488-500. doi:10.1093/cvr/cvz010.
44. Mohsin S, Khan M, Nguyen J, et al. Rejuvenation of human cardiac progenitor cells with Pim-1kinase.CircRes.2013Oct25;113(10):1169-79.doi:10.1161/CIRCRESAHA.113.302302.
45. Zhang LX, DeNicola M, Qin X, et al. Specific inhibition of HDAC4 in cardiac progenitor cells enhances myocardial repairs. Am J Physiol Cell Physiol. 2014 Aug 15;307(4):C358-72. doi:10.1152/ajpcell.00187.2013.
46. Eulalio A, Mano M, Dal Ferro M, et al. Functional screening identifies miRNAs inducing cardiac regeneration. Nature. 2012 Dec 20;492(7429):376-81. doi:10.1038/nature11739.
47. Lesizza P, Prosdocimo G, Martinelli V, et al. Single-Dose Intracardiac Injection of Pro-Regenerative MicroRNAs Improves Cardiac Function After Myocardial Infarction. Circ Res. 2017 14;120(8):1298-304. doi:10.1161/CIRCRESAHA.116.309589.
48. Rojas SV, Kensah G, Rotaermel A, et al. Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction. PLoS One. 2017 May 11;12(5):e0173222. doi:10.1371/journal.pone.0173222.
49. Kurotsu S, Suzuki T, Ieda M. Direct Reprogramming, Epigenetics, and Cardiac Regeneration. J Card Fail. 2017;23(7):552-7. doi:10.1016/j.cardfail.2017.05.009.
50. Werner JH, Rosenberg JH, Um JY, et al. Molecular discoveries and treatment strategies by direct reprogramming in cardiac regeneration. Transl Res. 2019 Jan;203:73-87. doi:10.1016/j.trsl.2018.07.012.
Рецензия
Для цитирования:
Парфенова Е.В. Стволовые клетки сердца: факт или фантазия? Российский кардиологический журнал. 2019;(11):84-90. https://doi.org/10.15829/1560-4071-2019-11-84-90
For citation:
Parfenova E.V. Heart stem cells: fact or fantasy? Russian Journal of Cardiology. 2019;(11):84-90. (In Russ.) https://doi.org/10.15829/1560-4071-2019-11-84-90
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