Neoangiogenesis after direct intramyocardial implantation of bone marrow-derived stem cells in a patient with severe coronary artery disease ineligible for percutaneous or surgical revascularization

• Authors: Bugra Harmandar , Turkan Tansel , Ertan Onursal , Nuray Gurses , Sevgi Besisik , Deniz Sargin
• Languages of publication: EN

Abstracts

EN

Bone marrow-derived stem cells (BMSC) may be an alternative for the treatment of patients with severe coronary artery disease ineligible for either percutaneous or surgical revascularization. This case report presents a 65-year-old male patient with untreatable angina pectoris (Canadian Cardiovascular Society Class III) and severe coronary artery disease. A mixture of BMSC containing approximately 3×106 CD34+ cells was directly injected into preoperatively determined ischemic regions of the myocardium by median sternotomy. At baseline, at 3 months, and at 1 year of follow-up, echocardiography (demonstrating wall motions of 16 segments), single-photon emission computed tomography, and coronary angiography (at baseline and at 1 year) were performed to assess myocardial perfusion, left ventricular (LV) function and coronary anatomy. The patient reached Canadian Cardiovascular Society Class I after 6 months of cell implantation. The ejection fraction increased from 34% to 37% at the third month and 40% at 1 year of follow-up. At 1 year of follow-up, preoperatively akinetic mid-base septum and anteroseptal regions progressed to mild hipokinesia and severe hypokinetic mid-base-apical anterior regions and apical lateral-inferior regions became normokinesia. Single-photon emission computed tomography revealed a visible improvement in anterior and lateral segments at 1 year of follow-up. Coronary angiography showed newly developed collateral arteries at 1 year of follow-up. BMSC transplantation in a patient with severe coronary artery disease resulted in increase of LV ejection fraction, an increase of the perfusion of ischemic myocardial regions, and improvement in wall motion defects without any adverse events.

Keywords

EN

Coronary artery disease; Stem cells; Myocardial regeneration; Angiogenesis; Myocardial injury

• Publisher: De Gruyter Open
• Journal: Open Medicine
• Year: 2009
• Volume: 4
• Issue: 3
• Pages: 279-285

Dates

published

1 - 9 - 2009

online

3 - 7 - 2009

Contributors

author

Bugra Harmandar

• Department of Cardiovascular Surgery, Istanbul University, Istanbul Medical Faculty, 34093, Capa, Istanbul, Turkey

author

Turkan Tansel

• Department of Cardiovascular Surgery, Istanbul University, Istanbul Medical Faculty, 34093, Capa, Istanbul, Turkey

author

Ertan Onursal

• Department of Cardiovascular Surgery, Istanbul University, Istanbul Medical Faculty, 34093, Capa, Istanbul, Turkey

author

Nuray Gurses

• Department of Haematology, Istanbul University, Istanbul Medical Faculty, 34093, Capa, Istanbul, Turkey

author

Sevgi Besisik

• Department of Haematology, Istanbul University, Istanbul Medical Faculty, 34093, Capa, Istanbul, Turkey

author

Deniz Sargin

• Department of Haematology, Istanbul University, Istanbul Medical Faculty, 34093, Capa, Istanbul, Turkey

References

• [1] Wollert KC, Drexler H. Clinical applications of stem cells for the heart. Circ Res 2005 Feb 4;96(2):151–163 http://dx.doi.org/10.1161/01.RES.0000155333.69009.63[Crossref]
• [2] Fuchs S, Satler LF, Kornowski R, Okubagzi P, Weisz G, Baffour R, Waksman R, Weissman NJ, Cerqueira M, Leon MB, Epstein SE. Cathater-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol 2003 May 21;41(10):1721–1724 http://dx.doi.org/10.1016/S0735-1097(03)00328-0[Crossref]
• [3] Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Silva GV, Mesquita CT, Belém L, Vaughn WK, Rangel FO, Assad JA, Carvalho AC, Branco RV, Rossi MI, Dohmann HJ, Willerson JT. Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 2004 Sep 14;110(11 Suppl 1):II213–II218
• [4] Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT, Rossi MI, Carvalho AC, Dutra HS, Dohmann HJ, Silva GV, Belém L, Vivacqua R, Rangel FO, Esporcatte R, Geng YJ, Vaughn WK, Assad JA, Mesquita ET, Willerson JT. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 2003 May 13;107(18):2294–2302 http://dx.doi.org/10.1161/01.CIR.0000070596.30552.8B[Crossref]
• [5] Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP. Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 2003 Jan 4;361(9351):47 http://dx.doi.org/10.1016/S0140-6736(03)12111-3[Crossref]
• [6] Hamano K, Nishida M, Hirata K, Mikamo A, Li TS, Harada M, Miura T, Matsuzaki M, Esato K. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J 2001 Sep;65(9):845–847 http://dx.doi.org/10.1253/jcj.65.845[Crossref]
• [7] Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989 Sep–Oct;2(5):358–367
• [8] Beeres SL, Bax JJ, Kaandorp TA, Zeppenfeld K, Lamb HJ, Dibbets-Schneider P, Stokkel MP, Fibbe WE, de Roos A, van der Wall EE, Schalij MJ, Atsma DE. Usefulness of intramyocardial injection of autologous bone marrow-derived mononuclear cells in patients with severe angina pectoris and stress-induced myocardial ischemia. Am J Cardiol. 2006 May 1;97(9):1326–1331 http://dx.doi.org/10.1016/j.amjcard.2005.11.068[Crossref]
• [9] Briguori C, Reimers B, Sarais C, Napodano M, Pascotto P, Azzarello G, Bregni M, Porcellini A, Vinante O, Zanco P, Peschle C, Condorelli G, Colombo A. Direct intramyocardial percutaneous delivery of autologous bone marrow in patients with refractory myocardial angina. Am Heart J. 2006 Mar;151(3):674–680 http://dx.doi.org/10.1016/j.ahj.2005.04.033[Crossref]
• [10] Schächinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H, Dimmeler S, Zeiher AM. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol. 2004 Oct 19;44(8):1690–1699. http://dx.doi.org/10.1016/j.jacc.2004.08.014[Crossref]
• [11] Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, Hecker H, Schaefer A, Arseniev L, Hertenstein B, Ganser A, Drexler H. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months’ followup data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation. 2006 Mar 14;113(10):1287–1294 http://dx.doi.org/10.1161/CIRCULATIONAHA.105.575118[Crossref]
• [12] Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Bone marrow cells regenerate infarcted myocardium. Nature 2001 Apr 5;410(6829):701–705. http://dx.doi.org/10.1038/35070587[Crossref]
• [13] Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Schümichen C, Nienaber CA, Freund M, Steinhoff G. Autologous bonemarrow stem-cell transplantation for myocardial regeneration. Lancet 2003 Jan 4;361(9351):45–46. http://dx.doi.org/10.1016/S0140-6736(03)12110-1[Crossref]
• [14] Stamm C, Kleine HD, Choi YH, Dunkelmann S, Lauffs JA, Lorenzen B, David A, Liebold A, Nienaber C, Zurakowski D, Freund M, Steinhoff G. Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. J Thorac Cardiovasc Surg. 2007 Mar;133(3):717–725 http://dx.doi.org/10.1016/j.jtcvs.2006.08.077[Crossref]
• [15] Pompilio G, Steinhoff G, Liebold A, Pesce M, Alamanni F, Capogrossi MC, Biglioli P. Direct minimally invasive intramyocardial injection of bone marrow-derived AC133+ stem cells in patients with refractory ischemia: preliminary results. Thorac Cardiovasc Surg. 2008 Mar;56(2):71–76 http://dx.doi.org/10.1055/s-2007-989351[Crossref][WoS]
• [16] Klein HM, Ghodsizad A, Marktanner R, Poll L, Voelkel T, Mohammad Hasani MR, Piechaczek C, Feifel N, Stockschlaeder M, Burchardt ER, Kar BJ, Gregoric I, Gams E. Intramyocardial implantation of CD133+ stem cells improved cardiac function without bypass surgery. Heart Surg Forum. 2007;10(1):E66–9 http://dx.doi.org/10.1532/HSF98.20061054[WoS][Crossref]
• [17] Archundia A, Aceves JL, López-Hernández M, Alvarado M, Rodriguez E, Díaz Quiroz G, Páez A, Rojas FM, Montaño LF. Direct cardiac injection of G-CSF mobilized bone-marrow stem-cells improves ventricular function in old myocardial infarction. Life Sci. 2005 Dec 5;78(3):279–283. Epub 2005 Sep 23 http://dx.doi.org/10.1016/j.lfs.2005.04.080[Crossref]
• [18] Strauer BE, Brehm M, Zeus T, Köstering M, Hernandez A, Sorg RV, Kögler G, Wernet P. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002 Oct 8;106(15):1913–1918 http://dx.doi.org/10.1161/01.CIR.0000034046.87607.1C[Crossref]
• [19] Fernández-Avilés F, San Román JA, García-Frade J, Fernández ME, Peñarrubia MJ, de la Fuente L, Gómez-Bueno M, Cantalapiedra A, Fernández J, Gutierrez O, Sánchez PL, Hernández C, Sanz R, García-Sancho J, Sánchez A. Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res. 2004 Oct 1;95(7):742–748. Epub 2004 Sep 9 http://dx.doi.org/10.1161/01.RES.0000144798.54040.ed[Crossref]
• [20] Kuethe F, Richartz BM, Sayer HG, Kasper C, Werner GS, Höffken K, Figulla HR. Lack of regeneration of myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans with large anterior myocardial infarctions. Int J Cardiol. 2004 Oct;97(1):123–127 http://dx.doi.org/10.1016/j.ijcard.2004.05.002[Crossref]

Identifiers

DOI

10.2478/s11536-009-0035-4