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Stem Cell Res Ther. 2017 Oct 16;8(1):231. doi: 10.1186/s13287-017-0680-5.

Effects of timing on intracoronary autologous bone marrow-derived cell transplantation in acute myocardial infarction: a meta-analysis of randomized controlled trials.

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Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People's Republic of China.
Present address: Department of Cardiology, The Fifth People's Hospital of Dalian City, Dalian, People's Republic of China.
Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, People's Republic of China.



Several cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the timing of transplantation remains controversial. We conducted a meta-analysis of randomized controlled trials to investigate the effects of timing on bone marrow-derived cell (BMC) therapy in acute myocardial infarction (AMI).


A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine databases from January 2000 to June 2017 was performed on randomized controlled trials with at least a 3-month follow-up for patients with AMI undergoing emergency percutaneous coronary intervention (PCI) and receiving intracoronary BMC transfer thereafter. The defined end points were left ventricular (LV) ejection fraction, LV end-diastolic and end-systolic index. The data were analyzed to evaluate the effects of timing on BMC therapy.


Thirty-four RCTs comprising a total of 2,307 patients were included; the results show that, compared to the control group, AMI patients who received BMC transplantation showed significantly improved cardiac function. BMC transplantation 3-7 days after PCI (+3.32%; 95% CI, 1.91 to 4.74; P < 0.00001) resulted in a significant increase of left ventricular ejection fraction (LVEF). As for the inhibitory effect on ventricular remodeling, BMC transplantation 3-7 days after PCI reduced LV end-diastolic indexes (-4.48; 95% CI, -7.98 to -0.98; P = 0.01) and LV end-systolic indexes (-6.73; 95% CI, -11.27 to -2.19; P = 0.004). However, in the groups who received BMC transplantation either within 24 hours or later than 7 days there was no significant effect on treatment outcome. In subgroup analysis, the group with LVEF ≤ 50% underwent a significant decrease in LV end-diastolic index after BMC transplantation (WMD = -3.29, 95% CI, -4.49 to -2.09; P < 0.00001); the decrease was even more remarkable in the LV end-systolic index after BMC transplantation in the group with LVEF ≤ 50% (WMD = -5.25, 95% CI, -9.30 to -1.20; P = 0.01), as well as in patients who received a dose of 10^7-10^8 cells (WMD = -12.99, 95% CI, -19.07 to -6.91; P < 0.0001). In the group with a follow-up of more than 12 months, this beneficial effect was significant and increased to a more pronounced effect of +3.58% (95% CI, 1.55 to 5.61; P = 0.0006) when compared with control.


In this meta-analysis, BMC transfer at 3 to 7 days post-AMI was superior to transfer within 24 hours or more than 7 days after AMI in improving LVEF and decreasing LV end-systolic dimensions or LV end-diastolic dimensions. It is more effective in patients with lower baseline LVEF (≤50%) and the effect can last more than 12 months.


Acute myocardial infarction (AMI); Bone marrow-derived cells (BMCs); Cell therapy; Cells; Meta-analysis

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