A Systematic Review and Meta-Analysis: Safety and Efficacy of Mesenchymal Stem Cells Therapy for Heart Failure
Authors: Shen Tiantian , Xia Lin , Dong Wenliang , Wang Jiaxue , Su Feng , Niu Suping , Wang Qian , Fang Yi 
Published: August 2020

Background:
Preclinical and clinical evidence suggests that mesenchymal stem cells
(MSCs) may be beneficial in treating Heart Failure (HF). However, the effects of stem cell therapy in
patients with heart failure is an ongoing debate and the safety and efficacy of MSCs therapy are not
well-known. We conducted a systematic review of clinical trials that evaluated the safety and efficacy
of MSCs for HF. This study aimed to assess the safety and efficacy of MSCs therapy compared to the
placebo in heart failure patients.

Methods:
We searched PubMed, Embase, Cochrane library systematically, with no language restrictions.
Randomized Controlled Trials (RCTs) assessing the influence of MSCs treatment function controlled
with placebo in heart failure were included in this analysis. We included RCTs with data on
safety and efficacy in patients with heart failure after mesenchymal stem cell transplantation. Two
investigators independently searched the articles, extracted data, and assessed the quality of the included
studies. Pooled data was performed using the fixed-effect model or random-effect model by the
use of Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included
studies. The primary outcome was safely assessed by death and rehospitalization and the secondary
outcome was efficacy, which was assessed by six-minute walk distance and Left Ventricular Ejection
Fraction (LVEF), Left Ventricular End-systolic Volume (LVESV), Left Ventricular End-diastolic
Volume (LVEDV) and Brain Natriuretic Peptide (BNP).

Results:
A total of twelve studies were included, involving 823 patients who underwent MSCs or placebo
treatment. The overall rate of death showed a trend of reduction of 27% (RR [CI]=0.73 [0.49, 1.09], p=0.12)
in the MSCs treatment group. The incidence of rehospitalization was reduced by 47% (RR [CI]=0.53[0.38,
0.75], p=0.0004). The patients in the MSCs treatment group realised an average of 117.01m (MD [95%
CI]=117.01m [94.87, 139.14], p<0.00001) improvement in 6MWT. MSCs transplantation significantly improved
Left Ventricular Ejection Fraction (LVEF) by 5.66 % (MD [95% CI]=5.66 [4.39, 6.92], p<0.00001),
decreased Left Ventricular End-Systolic Volume (LVESV) by 14.75 ml (MD [95% CI]=-14.75 [-16.18, -
12.83], p<0.00001) and Left Ventricular End-Diastolic Volume (LVEDV) by 5.78 ml (MD [95% CI]=-
5.78[-12.00, 0.43], p=0.07), in the MSCs group, BNP was decreased by 133.51 pg/ml MD [95% CI]= -
133.51 [-228.17,-38.85], p=0.54, I2= 0.0%) than did in the placebo group.

Conclusions:
Our results suggested that mesenchymal stem cells as a regenerative therapeutic approach
for heart failure are safe and effective by virtue of their self-renewal potential, vast differentiation capacity
and immune modulating properties. Allogenic MSCs have superior therapeutic effects and intracoronary
injection is the optimum delivery approach. In the tissue origin, patients who received
treatment with umbilical cord MSCs seem more effective than bone marrow MSCs. As to dosage injected,
(1-10)*10^8 cells were of better effect.