Received:03 February 2019,
Published:15 August 2019
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Wenming CHEN, Minghui JIAN, Zhimei QIU, et al. Effect of bone marrow mesenchymal stem cells modified with Toll-like receptor 4 on cardiac function in rats after acute myocardial infarction[J]. Journal of Third Military Medical University, 2019, 41(15): 1438-1444.
Wenming CHEN, Minghui JIAN, Zhimei QIU, et al. Effect of bone marrow mesenchymal stem cells modified with Toll-like receptor 4 on cardiac function in rats after acute myocardial infarction[J]. Journal of Third Military Medical University, 2019, 41(15): 1438-1444. DOI: 10.16016/j.1000-5404.201902029.
Objective
2
To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) modified with Toll-like receptor 4 (TLR4) on cardiac function in rats after acute myocardial infarction.
Methods
2
BMSCs were isolated from rat bone marrow and then cultured
in vitro
. The recombinant lentivirus vector carrying the target gene (Lv-EGFP-TLR4) and empty virus vector (Lv-EGFP) were transfected into BMSCs respectively. The expression of TLR4 in the supernatant of BMSCs cells transfected with Lv-EGFP-TLR4 was detected by ELISA. Adult SD rats were randomly divided into 3 groups (
n
=18): control group
Lv-EGFP-BMSCs group and Lv-EGFP-TLR4-BMSCs group. Lv-EGFP-BMSCs and Lv-EGFP-TLR4-BMSCs were injected into the periphery of myocardial infarction in rats
respectively. The control group was injected with the same amount of PBS. On the 7th day of transplantation
the expression of EGFP positive cells was tracked by fluorescence microscopy
and the express
ion of TLR4 was detected by Western blotting. Cardiac function was measured by echocardiography on 28 d after transplantation. Myocardial collagen fibrosis was observed by HE and MASSON staining. Serum levels of procollagen type Ⅰ carboxyl terminal peptide (PICP) and procollagen type Ⅲ amino terminal peptide (PⅢNT) were measured by ELISA.
Results
2
After transfection of BMSCs with Lv-EGFP-TLR4
the expression of TLR4 was increased significantly in the supernatant of BMSCs
and reached 31.55 pg/mL in 48 h after transfection. On the 7th day of cell transplantation
the green fluorescence intensity of BMSCs labeled with EGFP in infarct area was significantly higher in Lv-EGFP-TLR4-BMSCs group than in Lv-EGFP-BMSCs group
and no EGFP expression was seen in control group
and the expression of TLR4 protein was also significantly higher than that in Lv-EGFP-BMSCs group (
P
<
0.01). On the 28th day of cell transplantation
the Lv-EGFP-TLR4-BMSCs group showed significantly higher left ventricular ejection fraction and short-axis shortening rate when compared with the Lv-EGFP-BMSCs group
but left ventricular end-systolic diameter (LVDs
5.41±0.71) and left ventricular end-diastolic diameter (LVDd
7.11±0.79) were statistically decreased than the other group (6.66±0.91
8.06±0.9
P
<
0.01) The Lv-EGFP-TLR4-BMSCs group also had significantly lower serum levels of PICP (72.88
vs
83.79 μg/L) and PⅢNT (7.33
vs
9.51 μg/L) than those in Lv-EGFP-BMSCs group (
P
<
0.05). The severity of myocardial fibrosis in Lv-EGFP-TLR4-BMSCs group was also significantly lower than that in Lv-EGFP-BMSCs group.
Conclusion
2
Transplantation of TLR4 modified BMSCs can treat myocardial infarction
attenuate the severity of myocardial fibrosis
and thereby improve the cardiac function of myocardial infarction rats.
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