Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model

Chun Mei Qi, Gen Shan Ma, Nai Feng Liu, Cheng Xing Shen, Zhong Chen, Xiao Jun Liu, Yao Peng Hu, Xiao Li Zhang, Gao Jun Teng, Sheng Hong Ju, Ming Ma, Yao Liang Tang

Research output: Contribution to journalArticle

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Abstract

Background: Mesenchymal stem cells (MSCs) transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs (MR-MSCs) and monitor the restorative effects of MR-MSCs with magnetic resonance (MR) imaging. Methods: Acute myocardial infarction (AMI) was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat (SPSS version 12.01). Results: A total of 26 swine were divided into four groups (sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7). MSCs, MR-MSCs (107 cells) or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction (LVEF) was slightly increased in the AMI group ((41.87±2.45)% vs (39.04±2.80)%, P >0.05), but significantly improved in the MR-MSCs group ((56.85±1.29)% vs (40.67±2.00)%, P <0.05) and unlabeled group ((55.38±1.07)% vs (41.78±2.08)%, P <0.05) at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group. Conclusion: Transplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2-month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.

Original languageEnglish (US)
Pages (from-to)544-550
Number of pages7
JournalChinese Medical Journal
Volume121
Issue number6
StatePublished - Apr 6 2008

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Mesenchymal Stromal Cells
Swine
Transplantation
Myocardial Infarction
Magnetic Resonance Spectroscopy
Mesenchymal Stem Cell Transplantation
Magnetic Resonance Imaging
Western Blotting
Balloon Occlusion
Troponin T
Tissue Inhibitor of Metalloproteinase-1
Myosin Heavy Chains
Matrix Metalloproteinase 2
Cell- and Tissue-Based Therapy
Cardiac Myocytes
Stroke Volume
Coronary Vessels
Myocardium
Stem Cells
Staining and Labeling

Keywords

  • Contrast media
  • Magnetic resonance imaging
  • Mesenchymal stem cell
  • Myocardial infarction
  • Ventricular function

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model. / Qi, Chun Mei; Ma, Gen Shan; Liu, Nai Feng; Shen, Cheng Xing; Chen, Zhong; Liu, Xiao Jun; Hu, Yao Peng; Zhang, Xiao Li; Teng, Gao Jun; Ju, Sheng Hong; Ma, Ming; Tang, Yao Liang.

In: Chinese Medical Journal, Vol. 121, No. 6, 06.04.2008, p. 544-550.

Research output: Contribution to journalArticle

Qi, CM, Ma, GS, Liu, NF, Shen, CX, Chen, Z, Liu, XJ, Hu, YP, Zhang, XL, Teng, GJ, Ju, SH, Ma, M & Tang, YL 2008, 'Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model', Chinese Medical Journal, vol. 121, no. 6, pp. 544-550.
Qi, Chun Mei ; Ma, Gen Shan ; Liu, Nai Feng ; Shen, Cheng Xing ; Chen, Zhong ; Liu, Xiao Jun ; Hu, Yao Peng ; Zhang, Xiao Li ; Teng, Gao Jun ; Ju, Sheng Hong ; Ma, Ming ; Tang, Yao Liang. / Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model. In: Chinese Medical Journal. 2008 ; Vol. 121, No. 6. pp. 544-550.
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abstract = "Background: Mesenchymal stem cells (MSCs) transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs (MR-MSCs) and monitor the restorative effects of MR-MSCs with magnetic resonance (MR) imaging. Methods: Acute myocardial infarction (AMI) was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat (SPSS version 12.01). Results: A total of 26 swine were divided into four groups (sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7). MSCs, MR-MSCs (107 cells) or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction (LVEF) was slightly increased in the AMI group ((41.87±2.45){\%} vs (39.04±2.80){\%}, P >0.05), but significantly improved in the MR-MSCs group ((56.85±1.29){\%} vs (40.67±2.00){\%}, P <0.05) and unlabeled group ((55.38±1.07){\%} vs (41.78±2.08){\%}, P <0.05) at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group. Conclusion: Transplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2-month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.",
keywords = "Contrast media, Magnetic resonance imaging, Mesenchymal stem cell, Myocardial infarction, Ventricular function",
author = "Qi, {Chun Mei} and Ma, {Gen Shan} and Liu, {Nai Feng} and Shen, {Cheng Xing} and Zhong Chen and Liu, {Xiao Jun} and Hu, {Yao Peng} and Zhang, {Xiao Li} and Teng, {Gao Jun} and Ju, {Sheng Hong} and Ming Ma and Tang, {Yao Liang}",
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T1 - Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model

AU - Qi, Chun Mei

AU - Ma, Gen Shan

AU - Liu, Nai Feng

AU - Shen, Cheng Xing

AU - Chen, Zhong

AU - Liu, Xiao Jun

AU - Hu, Yao Peng

AU - Zhang, Xiao Li

AU - Teng, Gao Jun

AU - Ju, Sheng Hong

AU - Ma, Ming

AU - Tang, Yao Liang

PY - 2008/4/6

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N2 - Background: Mesenchymal stem cells (MSCs) transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs (MR-MSCs) and monitor the restorative effects of MR-MSCs with magnetic resonance (MR) imaging. Methods: Acute myocardial infarction (AMI) was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat (SPSS version 12.01). Results: A total of 26 swine were divided into four groups (sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7). MSCs, MR-MSCs (107 cells) or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction (LVEF) was slightly increased in the AMI group ((41.87±2.45)% vs (39.04±2.80)%, P >0.05), but significantly improved in the MR-MSCs group ((56.85±1.29)% vs (40.67±2.00)%, P <0.05) and unlabeled group ((55.38±1.07)% vs (41.78±2.08)%, P <0.05) at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group. Conclusion: Transplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2-month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.

AB - Background: Mesenchymal stem cells (MSCs) transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs (MR-MSCs) and monitor the restorative effects of MR-MSCs with magnetic resonance (MR) imaging. Methods: Acute myocardial infarction (AMI) was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat (SPSS version 12.01). Results: A total of 26 swine were divided into four groups (sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7). MSCs, MR-MSCs (107 cells) or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction (LVEF) was slightly increased in the AMI group ((41.87±2.45)% vs (39.04±2.80)%, P >0.05), but significantly improved in the MR-MSCs group ((56.85±1.29)% vs (40.67±2.00)%, P <0.05) and unlabeled group ((55.38±1.07)% vs (41.78±2.08)%, P <0.05) at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group. Conclusion: Transplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2-month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.

KW - Contrast media

KW - Magnetic resonance imaging

KW - Mesenchymal stem cell

KW - Myocardial infarction

KW - Ventricular function

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