Yonsei Med J.  2015 Nov;56(6):1522-1529. 10.3349/ymj.2015.56.6.1522.

Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

• Lee HW
• Lee HC
• Park JH
• Kim BW
• Ahn J
• Kim JH
• Park JS
• Oh JH
• Choi JH
• Cha KS
• Hong TJ
• Park TS
• Kim SP
• Song S
• Kim JY
• Park MH
• Jung JS

• KMID: 2345878
• DOI: http://doi.org/10.3349/ymj.2015.56.6.1522

Abstract

PURPOSE
Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model.
MATERIALS AND METHODS
ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBISPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed.
RESULTS
Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0+/-10.0 vs. -2.6+/-12.0, p=0.019; LVEF, -8.0+/-15.4 vs. -15.9+/-14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining.
CONCLUSION
Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model.

Keyword

Myocardial infarction; angiogenesis; mesenchymal stem cells; left ventricle remodeling; 99mTc MIBI

MeSH Terms

Adipose Tissue/cytology
Animals
Bone Marrow Cells/cytology/*metabolism
Chemokine CXCL12
Coronary Vessels
Female
Heart/physiopathology
Heart Ventricles
*Mesenchymal Stromal Cells
Myocardial Infarction/physiopathology/radionuclide imaging/*therapy
*Stem Cell Transplantation
Swine
Technetium Tc 99m Sestamibi/*pharmacology
Tomography, Emission-Computed, Single-Photon/*methods
Troponin T
*Ventricular Function, Left
Chemokine CXCL12
Technetium Tc 99m Sestamibi
Troponin T

Figure

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  Fig. 1 Porcine acute myocardial infarction (MI) model. Transmural MI was induced with balloon occlusion [angioplasty over-the-wire (OTW) coaxial balloon, 2.5×20 mm] at the mid left anterior descending artery (LAD) after a second diagonal branch for 3 h under electrocardiography (ECG) and hemodynamic monitoring.

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  Fig. 2 Engrafted adipose tissue-derived stem cells tagged with CM-dil in the border zone after 4 weeks (original magnification, ×40). ADSC, adipose tissue-derived stem cell.

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  Fig. 3 Nuclear imaging. The degree of improvement of the perfusion defect at follow-up examination was significantly greater in the ADSC group on 99mTc MIBI-scan. ADSC, adipose tissue-derived stem cell; MIBI, methoxyisobutylisonitrile.

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  Fig. 4 Comparison of infarct area from gross specimens. Infarct territory was much smaller in the ADSC group. ADSC, adipose tissue-derived stem cell.

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  Fig. 5 Identification of phenotype of engrafted adipose tissue-derived stem cells in the infarct border zone by immunohistochemical staining for SDF-1, CD44, vWF, CD31 (original magnification, ×200). Staining with SDF-1, CD44, vWF, and CD31 were more enhanced in the ADSC group compared to the control group. Pattern of the TnT staining was not different between the two groups. ADSC, adipose tissue-derived stem cell; vWF, von Willebrand factor; SDF-1, stromal cell-derived factor-1.

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  Fig. 6 Comparison of capillary density after immunohistochemical staining for vWF (original magnification, ×200). Capillary density was higher in the ADSC group than in the control. ADSC, adipose tissue-derived stem cell; vWF, von Willebrand factor.

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