Tissue-source effect on mesenchymal stem cells as living biodrugs for heart failure: Systematic review and meta-analysis

Table 1 Baseline characteristics of randomized clinical trials included in the meta-analysis for mortality in umbilical-cord-derived mesenchymal-stem-cell-based heart therapy, n (%)

		Gao et al[21], 2015 (China)	He et al[18], 2020 (China)	Zhao et al[26], 2015 (China)	Bartolucci et al[28], 2017 (Chile)	Ulus et al[25], 2020 (Türkiye)
Study type		RCT	RCT	RCT	RCT	Open-label RCT
Phase		I/II	I	I/II	I/II	I/II
Sample size	Total	116	50	59	30	41
	Intervention (male)	58 (94.8)	32 (78.12)	30 (80.0)	15 (80.0)	25 (100)
	Control (male)	58 (87.9)	12 (58.30)	29 (65.5)	15 (93.3)	16 (100)
Mean age (mean ± SD)	Intervention	57.3 ± 9.90	59.6 (7.9)/63.6 (8.6)	52.90 ± 16.32	57.33 ± 10.05	61.8 ± 10
	Control	56.7 ± 12.95	65.2 (7.9)	53.21 ± 11.46	57.20 ± 11.64	65.3 ± 6.8
Mean BMI (mean ± SD)	Intervention	24.9 ± 2.28	25.5 ± 3.3 /24.4 ± 3.3	N/A	29.12 ± 2.88	26.5 ± 4.5
	Control	25.4 ± 2.28	23.59 ± 2.28	N/A	29.52 ± 4.00	26.6 ± 4.8
Number of smokers	Intervention	34 (58.6)	4 (25.0)/7 (43.8)	N/A	7 (46.7)	21 (84)
	Control	32 (55.2)	3 (25.0)	N/A	4 (26.7)	15 (88.2)
HTN	Intervention	33 (56.9)	10 (62.5)/14 (87.5)	N/A	7 (46.7)	15 (60)
	Control	26 (44.8)	9 (75.0)	N/A	8 (53.3)	11 (64.7)
DM	Intervention	17 (29.3)	8 (50.0)/4 (25.0)	N/A	5 (33.3)	16 (66.7)
	Control	14 (24.1)	8 (66.7)	N/A	7 (46.7)	9 (52.9)
NYHA; I (n), II (n), III (n), IV (n)	Intervention	N/A	III (4 / 8), IV (12 / 8)	N/A	2.03 ± 0.61	1.9 ± 0.44
	Control	N/A	III (7) IV (5)	N/A	1.67 ± 0.49	2.1 ± 0.37
Comparison		Placebo	CABG only	HF drugs only	Placebo	CABG only
Follow-up, months		1, 4, 12 and 18 mo	3, 6 and 12 mo	1 and 6 mo	3, 3, 6 and 12 mo	1, 3, 6 and 12 mo
Assessment modality (yes/no)	ECG	Yes	-	Yes	Yes	Yes
	Echo	Yes	-	Yes	Yes	Yes
	MRI	No	Yes - CMR	-	Yes - CMR	Yes
	Cardiac CT	Yes	-	-	-	No
	SPECT	Yes	-	-	-	Yes
Measured outcomes		Safety and adverse event (primary), efficacy, and LV functions LVEF (secondary)	Serious adverse events at 12 mo (primary), the efficacy of hUC-MSCs and collagen scaffold assessed according to the CV-CMR-based LVEF and infarct size at 3, 6 and 12 mo after treatment, and NYHA (secondary)	Changes in LVEDD, LVEF, BNP, 6MWD, symptoms of HF, death, and adverse events	Safety: Adverse events after IV infusion -/-. Efficacy: (primary). Change in LVEF in ECHO, changes in - (LVESV) & (LVEDV) at ECHO; LVEF, LVESV, and LVEDV in CMR; NYHA score (secondary)	LVEF, LV remodeling, myocardial mass, 6MWD, NYHA score change

HUC-MSCs: Human umbilical cord mesenchymal stem cells; HT: Hypertension; DM: Diabetes mellitus; BMI: Body mass index; CABG: Coronary artery bypass grafting; HF: Heart failure; LV: Left ventricle; LVEF: Left ventricular ejection fraction; LVEDV: Left ventricular end diastolic volume; LVESV: Left ventricular end systolic volume; MI: Myocardial infarction; 6MWD: 6-min walking distance test; N/A: Not available; NYHA: New York Heart Association; PCI: Percutaneous coronary intervention; RCT: Randomized controlled trial; BNP: Brain natriuretic peptide; ECG: Electrocardiogram; Echo: Echocardiogram; MRI: Magnetic resonance ımaging; CT: Computed tomography; SPECT: Single-photon emission computed tomography.