Stem cell therapy for heart failure: Medical breakthrough, or dead end?

Table 1 Summary of landmark human clinical trials

Cell type	Clinical trial	Sample size	Results	Ref.
ESCs	ESCORT	6	Improvement in NYHA functional class, 6 min test and heart wall motion	[32]
iPSCs	Cyranoski, 2018	10	Trial results pending	[36]
	HEAL-CHF	5	Trial results pending	[36]
CSCs	CADUCEUS	31	Improvements in scar size, regional contractility and heart mass; no differences in EDV, ESV and LVEF between groups	[42]
BMMNCs	Perin et al[44], 2003	21	Improvements in LVEF, perfusion and contractility; Reductions in ESV	[44]
	TOPCARE-CHD	121	Improvements in global cardiac function and contractility, decreased BNP and mortality	[45]
	STAR-heart;	191	Improvements in LVEF, NYHA functional class and long-term mortality; Decreased LV preload, ESV and infarct area	[46]
	FOCUS-CCTRN	92	No improvements in LVEF, maximal O2 consumption and infarct size	[47]
BMMNCs and autologous MSCs	TAC-HFT	65	Decreased infarct size and improvements in 6 min walk test and regional function of the heart in MSC group only	[49]
CD133(+)	CARDIO33	60	No improvements in LV function or clinical symptoms	[50]
BMDSCs	Systematic review and meta-analysis	1907	Low-quality evidence that BMDSCs reduce mortality, improves LVEF and improves NYHA functional class	[51]
Autologous MSCs	MSC-HF	60	Improvements in LVEF, stroke volume and myocardial mass	[54]
Autologous and allogeneic MSCs	POSEIDON	30	Improvements in LV functions with reductions in adverse remodeling, infarct size	[55]
	POSEIDON-DCM	37	Greater improvements seen in allogeneic MSCs regarding functional capacity, quality of life, EF, 6 min walk test, and the Minnesota Living with HF questionnaire	[56]
Cardiopoietic	C-CURE	36	Improvements in LVEF, quality of life and decreased LVESV	[57]
	CHART-1	351	Decreased LVESV and LVEDV	[58]
Umbilical MSCs	RIMECARD	30	Improvements in LVEF but no improvements in LVESV or LVEDV	[60]
	Zhao et al[61], 2015	59	No improvements in LVEF but some improvements in the 6 min walk test, mortality rate and NT-pro brain natriuretic peptide levels	[61]
MPCs	DREAM-HF-1	566	Trial results pending	[64]
MSCs	Systematic review and meta-analysis	29 studies	Improvements in LVEF, LVESV, NYHA functional class, quality of life and exercise capacity	[65]
	Systematic review and meta-analysis	12 studies	No significant improvements in LVEF. Improvements in quality of life and the 6 min walk test	[52}
SMs	MAGIC	120 with 7 patients on f/u	No improvements in LVEF or global heart function	[68,69]
	MARVEL	23	No improvements in LV function; Moderate improvements in 6 min walk test	[71]

ESCs: Embryonic stem cells; NYHA: New York Heart Association; iPSCs: Induced pluripotent cells; CSCs: Cardiac stem cells; ESV: End-systolic volume; LVEF: Left ventricular ejection fraction; BMMNCs: Bone marrow mononuclear cells; MSCs: Mesenchymal stem cells; BMDSCs: Bone marrow-derived stem cells; MPCs: Mesenchymal precursor cells; HF: Heart failure; LVESV: Left Ventricular end systolic volume; MAGIC: Myoblast autologous grafting in ischemic cardiomyopathy; LV: Left ventricular; SMs: Skeletal myoblasts.

Table 2 Safety parameters of various stem cell types

Cell type	Safety parameters	Ref.
ESCs	Animal models → risk of ventricular arrhythmias but no concerns of immune rejection or teratoma formation; Positive safety profile in one human clinical trial – silent alloimmunization in 3 of 6 patients	[29,30,32,37]
iPSCs	No published human clinical trials completed; Derivatives pose risk of tumorigenicity	[36,54]
CSCs	Heavily compromised field of research due to lack of scientific integrity; Suggestions in positive safety profile of CDCs	[40,42]
BMDSCs	Positive safety profile demonstrated in allogeneic and autologous human clinical trials; Easy to harvest; Decrease in arrhythmogenic risk; Noteworthy increase in adverse events → CARDIO133 trial	[43,44,46,48,50]
MSCs	Positive safety profile demonstrated in multiple human clinical trials; Dyspnea, fatigue and chest tightness 1-mo post-transplantation, though small sample	[54-61]
SMs	Risk of ventricular arrhythmias	[68]

CSCs: Cardiac stem cells; iPSCs: Induced pluripotent cells; ESCs: Embryonic stem cells; MSCs: Mesenchymal stem cells; BMDSCs: Bone marrow-derived stem cells; BMMNCs: Bone marrow mononuclear cells; CDCs: Cardiosphere-derived cell; SMs: Skeletal myoblasts.