The Clinical Status of Stem Cell Therapy for Ischemic Cardiomyopathy

Table 1

Stem cell-based clinical studies in patients with ICM since 2010.

Study	Comparators	NO.	Condition	Delivery	Main results	Overall evaluation
CSCs
SCIPIO trial (2011) [25]	Auto CSCs versus control	16	EF ≤ 40%, phase I	IC	LVEF ↑, infarct size ↓	Improvement in LV systolic function, efficacy
CADUCEUS trial (2012) [26]	Auto CDCs versus standard care	31	MI, LVEF = 25–45%, phase I	IC	Scar mass ↓, viable mass ↑, regional contractility ↑, EDV-, ESV-, LVEF-, SAE-	Increase of viable myocardium, safe
SCIPIO trial (2012) [28]	Auto CSCs versus control	33	LVEF < 40%, phase I	IC	LVEF ↑, infarct size ↓, LV nonviable mass ↓, LV viable mass ↑, SAE-	Feasible, improvements in global and regional LV function
CADUCEUS trial (2014) [27]	Auto CDCs versus routine care	17	MI, phase I	IC	Scar size ↓, scar mass ↓, Viable mass ↑, SAE-	Safe and effective
MSCs
Hare et al. (2012) [29]	Allo MSCs versus auto MSCs versus placebo	30	ICM, phase I/II	TED	Allo group: LVEDV ↓; Auto group: 6-minute walk distance ↑; both: EF-, MVO2-, SAE-	Improvements in LV function, life quality, and LV reverse remodeling
TAC-HFT (2014) [30]	Auto MSCs versus placebo	65	ICM, LVEF < 50%	TED	LV chamber volume-, LVEF-, 6-minute walking distance ↑, infarct size ↓, SAE-	Safety and modest efficacy
DanCell study (2014) [31]	Auto BMSCs versus baseline	32	Systolic dysfunction, LVEF 33 ± 9%	IC	Multivariate regression analysis, CD34(+) cell survival rate ↑, SAE-	Beneficial on chronic ischemic HF for long-term survival
SEED-MSC (2014) [32]	Auto BMSCs versus control	80	AMI	IC	LVEF ↑, SAE-	Safety
POSEIDON (2014) [33]	MSCs versus baseline	30	Chronic ICM	TED	EF ↑, SAE-	Scar size reduction and better ventricular function
BMMNCs
STAR-heart study (2010) [34]	BMMNCs versus control	391	Chronic HF due to ICM, LVEF ≤ 35%	IC	LVEF ↑, exercise capacity ↑, oxygen uptake ↑, LV contractility ↑, long-term mortality ↓, SAE-	Improvements in LV performance, life quality, and survival
Hu et al. (2011) [35]	Auto BMMNCs versus placebo	60	Congestive HF due to severe ICM	Via CABG	LVEF ↑, LVESV ↓, wall motion index score ↑, 6-minutes walking distance ↑, SAE-	Efficacy, feasibility, and safety
Intrapatient comparison (2012) [36]	BMMNCs versus placebo	16	Chronic ICM	IM	Life quality ↑, LVESV ↓, LVEDV-, LVEF-, SAE-	Significant improvements in angina symptoms and MP
Antonitsis et al. (2012) [37]	Auto BMMNCs versus baseline	9	Severe ICM	CABG plus IM	LVEF ↑ at 3, 6, and 12 M, MP ↑ and infarct size ↓ at 6 and 12 M, SAE-	Feasibility and safety
FOCUS-CCTRN trial (2012) [38]	Auto BMMNCs versus placebo	153	Chronic ischemic HF, NYHA II–IV	TED	LVESV-, MVO2-, regional wall motion-, clinical improvement-, SAE-	No efficacy
Sürder et al. (2013) [39]	Auto BMMNCs versus placebo	200	STEMI	IC	LVEF-, SAE-	No efficacy
Heldman et al. (2014) [30]	Auto BMMNCs versus MSCs	65	ICM, LVEF < 50%, phase I/II	TED	6-minute walking distance ↑, infarct size ↓, LV chamber volume-, EF-, SAE-	Safety
END-HF (2014) [40]	Auto BMMNCs versus placebo	28	ICM, NYHA III-IV, LVEF < 40%	TED	LVEF-, LVESV-, LV infarct volume-, LV peri-infarct ischemic volume, SAE-	No improvements in LV function and remodeling, no efficacy
BMCs
Assmus et al. (2010) [41]	BMCs versus placebo	204	Reperfused AMI	IC	Regional LV contractility ↑, SAE-	Reduction of major adverse events, LV function improvement
TOPCARE-AMI trial (2011) [42]	CPCs versus BMCs versus baseline	59	Reperfused AMI	IC	LVEF ↑, infarct size ↓, LVESV-, LVEDV ↑, SAE-	Long-term safety and efficacy
Williams et al. (2011) [43]	Auto BMCs versus baseline	8	MI	IM	EDV ↓, ESV ↓, infarct size ↓, SAE-	Improvements in LV regional contractility and reverse remodeling
CD34^+ SCs
Wang et al. (2010) [44]	Auto CD34^+ SCs versus placebo	112	Intractable angina, CCSC III-IV	IC	Weekly angina episodes frequency ↓, exercise time ↑, MP ↑, SAE-	Safety and feasibility
Losordo et al. (2011) [45]	Auto CD34^+ SCs versus placebo	167	Refractory angina	IM	Weekly angina frequency ↓ and exercise tolerance ↑ in the low-dose group, SAE-	Safety and efficacy
Poglajen et al. (2014) [46]	Peripheral blood CD34^+ SCs versus medical therapy	31	ICM, phase I/II (LVEF < 40%)	TED	LVEF ↑, 6-minute walking distance ↑, N-terminal pro-B-type natriuretic peptide ↓, SAE-	Improvements in LV function and exercise capacity, efficacy
CD133^+ SCs
COMPARE-AMI trial (2010) [47]	Auto CD133^+ SCs versus placebo	14	PCI and LVEF < 50%, phase II	IC	LVEF ↑, LV function ↑, MP ↑, SAE-	Safety and efficacy
COMPARE-AMI trial (2010) [48]	Auto CD133^+ SCs versus placebo	20	AMI	IC	LVEF ↑, SAE-	Safety, feasibility, and efficacy
Kurbonov et al. (2013) [49]	Auto CD133^+ SCs versus control	15	ICM and MI	IC	Scar size ↓, effort tolerance ↑, physical endurance ↑, overall autonomy ↑, SAE-	Safety, feasibility, and efficacy
IMPACT-CABG pilot trial (2013) [50]	Auto CD133^+ SCs versus baseline	5	ICM, NYHA III	CABG plus IM	Systolic wall thickness ↑, the mean segmental wall thickness ↑, LVEF-, SAE-	Safety and feasibility
Assmann et al. (2014) [51]	Auto CD133^+ SCs + CABG versus CABG	42	Severe ICM, LVEF = 15%–35%	CABG plus TEP	LVEF ↑, angina frequncy ↓, life quality ↑, SAE-	Improvement in myocardial function, safe and feasible
Cardio133 trial (2014) [52]	Auto CD133^+ SCs versus placebo	60	Chronic ICM, LVEF < 35%	IM	6-min walking distance-, MLHFQ-, CCSC-, NYHA-, LVEF-, MP ↑, scar mass ↓, regional wall motion ↑, SAE-	No effects on global LV function and clinical symptoms
SMs
Fujita et al. (2011) [53]	Auto SMs versus baseline	4	Severe ICM	IM	Two patients with brain natriuretic peptide levels ↓ and MP ↑, SAE-	Feasibility, only marginal improvements
Brickwedel et al. (2014) [54]	Auto SMs versus placebo	7	ICM, phase II	Via CABG	High-dosage group: LVEF-, LV volumes ↓; low-dosage group: LV volumes-; SAE-	No improvement in LV function, safety

SCs: stem cells; NO.: number of patients; BMSCs: bone mesenchymal stem cells; CPCs: circulating blood-derived progenitor cells; M: month; W: week; IC: intracoronary; IV: intravenous; IM: intramyocardial; TEN: transendocardial; TEP: transepicardial; LV: left ventricular; LVEF: left ventricular ejection fraction; PCI: percutaneous coronary intervention; HF: heart failure; CBFR: coronary blood flow reserve; MLHFQ: Minnesota Living With Heart Failure Questionnaire; STEMI: ST-elevation myocardial infarction; HRV: heart rate variability; LVAD: left ventricular assist device; CABG: coronary artery bypass graft; MV: myocardial viability; MP: myocardial perfusion; VCF: LV velocity of shortening; CFR: coronary flow reserve; Auto: autologous; Allo: allogeneic; NYHA: New York Heart Association class; CCS: Canadian Cardiovascular Society; CCSC: Canadian Cardiovascular Society class; WMSI: Wall Motion Score Index; 24-h Holter ECG: twenty-four-hour electrocardiographic monitoring; SAE: serious adverse events.