Translational research of adult stem cell therapy

Table 1 Clinical Trials of mesenchymal stem cells, cardiosphere-derived cells and cardiac stem cells in heart disease

Trial name	Study design	No. of patients	Delivery method	Cell dose	End pointevaluation	Follow-up period	Outcome
MSCs
Chen et al[10]	Randomized, controlled study	MSC n = 34 Control n = 35	Intracoronary	48-60 × 109 cells	Echocardiography	3 and 6 mo	LVEF↑
POSEIDON[28]	Randomized, Pilot study	MSC n = 30 Auto vs Allo	Intramyocardial (transendocardial)	20, 100, 200 × 106 cells	Cardiac CT	12 mo	LVEF↔ LVEDV↓
PROMETHEUS[29]	Randomized, Pilot study	MSC n = 6 No control	Intramyocardial (transepicardial)	20, 200 × 106 cells	MRI	18 mo	LVEF↑ Scar size↓
C-CURE[30]	Randomized, controlled study	MSC n = 21 Control n = 15	Intramyocardial (transendocardial)	7 × 106 cells	Echocardiography	6 and 24 mo	LVEF↑ LVESV↓
CDCs
CADUCEUS[36,37]	Randomized, controlled study	CDC n = 17 Control n = 8	Intracoronary	12.5-25 × 106 cells	MRI	6 and 12 mo	LVEF↔ Scar size↓
ALCADIA	Pilot study	CDC n = 6 No control	Intracoronary	25-30 × 106 cells	MRI	12 mo	LVEF↑ Scar size↓
TICAP[38]	Randomized, controlled study	CDC n = 7 Control n = 7	Intracoronary	2-3 × 106 cells	MRI	18 mo	LVEF↑
CSCs
SCIPIO[50]	Randomized, controlled study	CSC n = 20 Control n = 13	Intracoronary	1 × 106 cells	Echocardiography MRI	12 mo	LVEF↑ Scar size↓

Auto: Autologous; Allo: Allogeneic; MSCs: Mesenchymal stem cells; CSCs: Cardiac stem cells; CDCs: Cardiosphere-derived cells; CT: Computed tomography; MRI: Magnetic resonance imaging.

Table 2 Alternative strategies of stem cell therapy

Enhancement of cell survival, mobilization and paracrine secretion

Pharmacology (Statins, etc.)

Genetic modification (Akt and Ang1, VEGF and SDF-1, HO-1, bFGF/IGF-1/BMP2)

Preconditioning (Hypoxia, TLR3 stimulation)

Combination of different cell types or delivery approaches

MSCs and CSCs

Stop-flow (infarct area) and global intracoronary infusion (viable area)

Others

Cell infusion immediate after revascularization (allogeneic MSCs, CDCs, etc.)

Repeated cell infusion

Stimulation of exosome release

Direct exosome (or microRNAs) injection

Cell therapy in hypertrophied myocardium or dysfunction due to congenital heart disease

MSCs: Mesenchymal stem cells; CSCs: Cardiac stem cells; CDCs: Cardiosphere-derived cells; VEGF: Vascular endothelial growth factor; SDF: Stromal cell-derived factor; bFGF: Basic fibroblast growth factor; IGF: Insulin-like growth factor; BMP2: Bone morphogenetic protein 2; HO-1: Heme-oxygenase 1; Ang1: Angiopoietin 1.