Despite the development of novel therapeutic strategies, cardiovascular diseases remain the main cause of morbidity and mortality worldwide. Many phase 1 and 2 clinical trials have reported the safety, feasibility and promising potential of stem cell transplantation, however, the optimal cell types, timing of infusion, cell dosage and routes of administration remain to be determined. This paper reviews the findings of various clinical studies and discusses the challenges facing the delivery of stem cell therapy in cardiovascular diseases.
SegersVFLeeRT: Stem-cell therapy for cardiac disease. Nature2008; 451: 937–942.
2.
SzmitkoPEFedakPWWeiselRD: Endothelial progenitor cells: new hope for a broken heart. Circulation2003; 107: 3093–3100.
3.
NesselmannCKaminskiASteinhoffG: Cardiac stem cell therapy. Registered trials and a pilot study in patients with dilated cardiomyopathy. Herz2011; 36: 121–134.
4.
AssmusBSchächingerVTeupeC: Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation2002; 106: 3009–3017.
5.
DonndorfPStrauerBESteinhoffG: Update on cardiac stem cell therapy in heart failure. Curr Opin Cardiol2012; 27: 154–160.
6.
WöhrleJMerkleNMailänderV: Results of intracoronary stem cell therapy after acute myocardial infarction. Am J Cardiol2010; 105: 804–812.
7.
BeitnesJOGjesdalOLundeK: Left ventricular systolic and diastolic function improve after acute myocardial infarction treated with acute percutaneous coronary intervention, but are not influenced by intracoronary injection of autologous mononuclear bone marrow cells: A 3 year serial echocardiographic sub-study of the randomized-controlled ASTAMI study. Eur J Echocardiogr2011; 12: 98–106.
8.
VrtovecBPoglajenGSeverM: Effects of intracoronary stem cell transplantation in patients with dilated cardiomyopathy. J Card Fail2011; 17: 272–281.
9.
MartinoHFOliveiraPSSouzaFC: A safety and feasibility study of cell therapy in dilated cardiomyopathy. Braz J Med Biol Res2010; 43: 989–995.
10.
BenettiFPeñherreraEMaldonadoT: Direct myocardial implantation of human fetal stem cells in heart failure patients: long-term results. Heart Surg Forum2010; 13: E31–E35.
11.
WangXXZhangFRShangYP: Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopathic pulmonary arterial hypertension: A pilot randomized controlled trial. J Am Coll Cardiol2007; 49: 1566–1571.
12.
LenkKAdamsVLurzP: Therapeutical potential of blood-derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia. Eur Heart J2005; 26: 1903–1909.
13.
AmadoLCSaliarisAPSchuleriKH: Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A2005; 102: 11474–11479.
14.
HareJMTraverseJHHenryTD: A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (Prochymal) after acute myocardial infarction. J Am Coll Cardiol2009; 54: 2277–2286.
BoyleAJWhitbournRSchlichtS: Intracoronary high-dose CD34+ stem cells in patients with chronic ischemic heart disease: A 12-month follow-up. Int J Cardiol2006; 109: 21–27.
18.
BartunekJVanderheydenMVandekerckhoveB: Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety. Circulation2005; 112: I178–I183.
19.
ManginasAGoussetisEKoutelouM: Pilot study to evaluate the safety and feasibility of intracoronary CD133+ and CD133−CD34+ cell therapy in patients with nonviable anterior myocardial infarction. Catheter Cardiovasc Interv2007; 69: 773–781.
20.
TenderaMWojakowskiWRuzyłłoW: Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial. Eur Heart J2009; 30: 1313–1321.
21.
KatritsisDGSotiropoulouPAKarvouniE: Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheter Cardiovasc Interv2005; 65: 321–329.
22.
TumaJFernández-ViñaRCarrascoA: Safety and feasibility of percutaneous retrograde coronary sinus delivery of autologous bone marrow mononuclear cell transplantation in patients with chronic refractory angina. J Transl Med2011; 9: 183.
23.
HerrerosJPrósperFPerezA: Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction. Eur Heart J2003; 24: 2012–2020.
BolliRChughARD'AmarioD: Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet2011; 378: 1847–1857.
26.
YangZZhangFMaW: A novel approach to transplanting bone marrow stem cells to repair human myocardial infarction: delivery via a noninfarct-relative artery. Cardiovasc Ther2010; 28: 380–385.
27.
HuSLiuSZhengZ: Isolated coronary artery bypass graft combined with bone marrow mononuclear cells delivered through a graft vessel for patients with previous myocardial infarction and chronic heart failure: A single-center, randomized, double-blind, placebo-controlled clinical trial. J Am Coll Cardiol2011; 57: 2409–2415.
28.
PatelANGeffnerLVinaRF: Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: A prospective randomized study. J Thorac Cardiovasc Surg2005; 130: 1631–1638.
29.
PerinECSilvaGVHenryTD: A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF). Am Heart J2011; 161: 1078–1087.
30.
GyöngyösiMLangIDettkeM: Combined delivery approach of bone marrow mononuclear stem cells early and late after myocardial infarction: the MYSTAR prospective, randomized study. Nat Clin Pract Cardiovasc Med2009; 6: 70–81.
31.
GowdakLHSchettertITRochitteCE: Early increase in myocardial perfusion after stem cell therapy in patients undergoing incomplete coronary artery bypass surgery. J Cardiovasc Transl Res2011; 4: 106–113.
32.
ChangSAKimHKLeeHY: Restoration of left ventricular synchronous contraction after acute myocardial infarction by stem cell therapy: new insights into the therapeutic implication of stem cell therapy for acute myocardial infarction. Heart2008; 94: 995–1001.
33.
PiepoliMFVallisaDArbasiM: Bone marrow cell transplantation improves cardiac, autonomic, and functional indexes in acute anterior myocardial infarction patients (Cardiac Study). Eur J Heart Fail2010; 12: 172–180.
34.
WollertKCMeyerGPLotzJ: Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet2004; 364: 141–148.
35.
ter HorstKW: Stem cell therapy for myocardial infarction: are we missing time?Cardiology2010; 117: 1–10.
36.
MengYZhangFBlairT: MRI of auto-transplantation of bone marrow-derived stem-progenitor cells for potential repair of injured arteries. PLoS One2012; 7: e31137.
37.
VanderheydenMVercauterenSMansourS: Time-dependent effects on coronary remodeling and epicardial conductance after intracoronary injection of enriched hematopoietic bone marrow stem cells in patients with previous myocardial infarction. Cell Transplant2007; 16: 919–925.
38.
Fernández-AvilésFSan RománJAGarcía-FradeJ: Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res2004; 95: 742–748.
