Search results
Ultimately, 18 clinical trials which investigating the effect of MSC therapy on AMI and ICM were included in the meta-analysis (n = 1055)[15–32]. Characteristics of the enrolled clinical studies are shown in Table 1.
In included trials, intracoronary infusion (IC)(n = 9) was the most common route of delivery stem cells, followed by transendocardial stem cell injection(TESI)(n = 6), intravenous infusion (IV) (n = 2) and directly intramyocardial injection (DI) (n = 1).Most of studies (n = 13) applied autologous/ allogeneic adult human bone marrow-derived mesenchymal cells [16, 17, 19–25, 27–29, 32]. 3 study investigated the use of autologous adipose tissue-derived mesenchymal cells[15, 30, 31].The remaining studies utilised varied allogeneic cell sources such as mesenchymal cells from umbilical cord blood (n = 2)[18, 26]. We performed a further meta-analysis on 11 AMI clinical trials (n = 550 patients)[15–25], characteristics of which are presented in Table 2, and performed on 7 ICM clinical trials(n = 505)[26–32], characteristics of which are depicted in Table 3.(More detailed information outlined in Supporting Information Appendix 1&2)
Primary outcomes——cardiac function
Left Ventricular Ejection Fraction (LVEF)
Compared to control, Patients receiving MSCs had a significantly increased in LVEF (SMD 0.37, 95% CI 0.23–0.50, I2 = 94.3%). MSC administered through intracoronary(IC), transendocardial stem cell injection(TESI), intravenous(IV) and directly intramyocardia(DI) have shown the potential to increase LVEF, when referring to the optional administration route, MSCs increased LVEF only when applied intracoronary injection (SMD 0.69,95% CI 0.47–0.91, I 2 = 96.6%)(Fig. 1), while when we performed a further meta-analysis within AMI and ICD patients, statistically significant difference was found in LVEF when administered different route
LVEF subgroup analysis
In AMI clinical trials, MSCs increased LVEF only when intracoronary injection was applied(SMD 0.88,95% CI 0.64-1.12, I 2 = 96.8%),and no difference in LVEF whether administered TESI (SMD 0.40,95% CI -0.37-1.17) or intravenously (SMD 0.01,95% CI -0.44-0.47). While in ICD clinical trials, it seems no difference in the increase in LVEF no matter applied which route. (SMD 0.10 , 95% CI 0.09-0.29, I 2 = 84.3%).
Using a sensitivity analysis, significant heterogeneity was found in the trials reported by Wang[22] and Gao et al [18] . I2 decreased from 95.7% to 68.7% when the data from Wang[22] and Gao et al. [18] were excluded.
Secondary outcomes——cardiac remodeling
LVEDV & LVESV
A total of 7 AMI studies and 4 ICD studies provided data on LVEDV. Patients who underwent intravenous or intracoronary decreased LVEDV significantly in AMI clinical trials. While in ICD clinical trials, the route included in was only TESI way, which limited our assessment of other pathways ,and TESI displayed an effective role on reducing cardiac remodeling (SMD -0.23,95% CI -0.43- -0.03). The above results were also appeared in LVESV.
Tertiary Outcomes——safety
Mortality
9 AMI studies and 5 ICM studies reported mortality. Patients no matter AMI or ICM showed no difference in mortality(RR 0.90,95%CI 0.56-1.43), the same result was observed no matter administered which route.
Sever adverse event
3 AMI studies and 4 ICM studies reported Sever adverse event. No significant difference in the risk of mortality between MSC and control groups, no matter in which group or administered which route. Interestingly, there was seems a trend to reduce sever adverse event when TESI was applied in ICM group, though it was not statistically significant.
Rehospitalization
6 AMI studies and 3 ICM studies provided data on readmission. In these trials, AMI group included IC and IV way, while only TESI is incorporate in ICM group, which makes it difficult to analysis the optimal route for reducing readmission between AMI or ICM group. Under such limited condition, we found that TESI showed a subtle advantage on reducing rehospitalization(SMD 0.6,95%CI 0.37-0.96).
Other outcomes
WMSI
In AMI group, WMSI was more significantly decreased when use IC than TESI injection, and there were no significant differences between MSC-and placebo-treated patients when applied IV injection(data not shown).WMSI was rarely reported in ICD group, thus we can’t know its real efficacy.
6min-walk
A total of 4 studies reported 6min-walk in ICD group, there were no significant differences between MSC-and placebo-treated patients when use DI or TESI way. 6min-walk was rarely reported in AMI group and it limit our conclusion.
No comparisons are made between other outcomes like infarct size, myocardial perfusion, NYHA class, quality of life due to its insufficient reports in studies included.
Risk of Bias Assessment
Two studies met all seven criteria for low risk of bias. Two studies fulfilled six of seven risk of bias criteria. Seven studies described a low risk of bias in randomization procedures. Four studies underwent allocation concealment with low risk of bias. For Double-blinding procedures, six studies met low risk of bias. One study had a high risk of bias due to incomplete outcome data reporting and three study had an unclear risk of bias for selective reporting. None of the studies were considered to be at high risk for other biases.