Paracrine Action Enhances the Effects of Autologous Mesenchymal Stem Cell Transplantation on Vascular Regeneration in Rat Model of Myocardial Infarction

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Paracrine Action Enhances the Effects of Autologous Mesenchymal Stem Cell Transplantation on Vascular Regeneration in Rat Model of Myocardial Infarction

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Paracrine Action Enhances the Effects of Autologous Mesenchymal Stem Cell Transplantation on Vascular Regeneration in Rat Model of Myocardial Infarction Yao Liang Tang, MD, PhD, Qiang Zhao, MD, Xinyu Qin, MD, Leping Shen, BS, Leilei Cheng, MD, Junbo Ge, MD, M. Ian Phillips, PhD, DsC The Annals of Thoracic Surgery Volume 80, Issue 1, Pages 229-237 (July 2005) DOI: 10.1016/j.athoracsur.2005.02.072 Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 (A) Phase-contrast micrograph of cultured mesenchymal stem cells at semiconfluent stage. (B) In vitro 5-bromo-2-deoxyruidine staining of the prelabeled mesenchymal stem cells, with most cells staining positive for 5-bromo-2-deoxyruidine (×40). (C) Myocardial injection site stained for 5-bromo-2-deoxyruidine at 2 weeks after intramyocardial injection of mesenchymal stem cells. 5-Bromo-2-deoxyruidine–positive graft mesenchymal stem cells are dispersed in the scar area of the left ventricle. Some 5-bromo-2-deoxyruidine–positive mesenchymal stem cells (arrows) are integrated into the endothelial cell layer of some new microvessels (×40). The Annals of Thoracic Surgery 2005 80, 229-237DOI: (10.1016/j.athoracsur.2005.02.072) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Effects of mesenchymal stem cell (MSC) implantation on neovasculature formation in ischemic hearts. Capillary densities were detected by immunostaining with the use of GSL-I-B4 antibody, and the vessel numbers were counted. Mesenchymal stem cell–transplanted hearts had more capillaries than the medium-treated control hearts. The Annals of Thoracic Surgery 2005 80, 229-237DOI: (10.1016/j.athoracsur.2005.02.072) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Western blot detection of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), stromal cell–derived factor-1α (SDF-1α), and Bax protein expression in rat hearts implanted with mesenchymal stem cells (MSCs) and medium alone (Medium) 2 weeks after implantation. Transplantation with mesenchymal stem cells induced greater basic fibroblast growth factor, vascular endothelial growth factor, and SDF-1α expression than that of the medium-treated control hearts, and Bax level in mesenchymal stem cell–treated hearts was markedly decreased compared with that in medium-treated control hearts. The bar graph shows relative expression of protein normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression (n = 4/group). The Annals of Thoracic Surgery 2005 80, 229-237DOI: (10.1016/j.athoracsur.2005.02.072) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 (A and B) Anatomic images of the ischemic hearts. (C and D) Transverse sections of the myocardial infarction hearts. A and C are from mesenchymal stem cell (MSC)-treated heart; B and D are from medium-treated heart. (E–H) Heart slices stained with Masson trichrome. Scar appears blue in Mason trichrome–stained slices. E and F are low-power views of transmural slices of the left ventricle stained with Masson trichrome. G and H are high-power views of the border zone of the infarct area. E and G are from a mesenchymal stem cell–treated heart that received mesenchymal stem cell injection. F and H are from a control heart that received medium injection. A greater number of new blood vessels were observed in the bone zone of mesenchymal stem cell–treated hearts (G) compared with medium-treated hearts (H). Infarct size was less in mesenchymal stem cell–treated hearts compared with medium-treated hearts (I). The Annals of Thoracic Surgery 2005 80, 229-237DOI: (10.1016/j.athoracsur.2005.02.072) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 5 Echocardiogram of the left ventricle. (A) Representative M-mode echocardiogram performed 2 months after implantation. Note the greater movement of the anterior wall of the mesenchymal stem cell (MSC)-injected heart compared with the medium-injected heart. (A = anterior wall; P = posterior wall.) (B) Left ventricular function measured by left ventricular fractional shortening (LVFS) 1 week after myocardial infarction and 2 months after implantation. Left ventricular fractional shortening was significantly higher in the mesenchymal stem cell–treated hearts compared with the medium-treated hearts. The Annals of Thoracic Surgery 2005 80, 229-237DOI: (10.1016/j.athoracsur.2005.02.072) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions