Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction

Liang Tang Yao, Qiang Zhao, Xinyu Qin, Leping Shen, Leilei Cheng, Junbo Ge, M. Ian Phillips

Research output: Contribution to journalArticle

339 Citations (Scopus)

Abstract

Background. There are several reports that engrafted mesenchymal stem cells (MSCs) stimulate angiogenesis in the ischemic heart, but the mechanism remains controversial. We hypothesize that transplantation of MSCs enhances vascular regeneration through a paracrine action. Methods. A transmural myocardial infarction was created by ligation of the left anterior descending coronary artery in rats. Those with an ejection fraction less than 0.70 1 week after myocardial infarction were included. Autologous MSCs (1 × 107; 0.2 mL) or culture medium (0.2 mL) was injected intramyocardially into the periinfarct zone (50 μL/injection at four sites; n = 20/group). At 2 weeks after transplantation, Western blot analysis was used to assay the paracrine factors and proapoptotic proteins. Echocardiography to assess heart function was performed on additional groups at 8 weeks after implantation. Results. The angiogenic factors basic fibroblast growth factor, vascular endothelial growth factor, and stem cell homing factor (stromal cell-derived factor -1α) increased in the MSC-treated hearts compared with medium-treated hearts. This was accompanied by a downregulation of proapoptotic protein Bax in ischemic myocardium. Similarly, capillary density increased about 40% in MSC-treated hearts compared with medium-treated hearts (p = 0.001). Left ventricular contractility, indicated by fractional shortening, improved in MSC-treated hearts at 2 months after implantation (MSCs: 48.6% ± 19.9%; medium: 18.7% ± 6.4%; p = 0.004). Conclusions. Autologous MSC transplantation attenuates left ventricular remodeling and improves cardiac performance. The major mechanism appears to be paracrine action of the engrafted cells, increasing angiogenesis and cytoprotection.

Original languageEnglish (US)
Pages (from-to)229-237
Number of pages9
JournalAnnals of Thoracic Surgery
Volume80
Issue number1
DOIs
StatePublished - Jul 1 2005

Fingerprint

Mesenchymal Stem Cell Transplantation
Blood Vessels
Regeneration
Mesenchymal Stromal Cells
Myocardial Infarction
Chemokine CXCL12
bcl-2-Associated X Protein
Ventricular Remodeling
Stem Cell Factor
Cytoprotection
Angiogenesis Inducing Agents
Fibroblast Growth Factor 2
Vascular Endothelial Growth Factor A
Ligation
Culture Media
Echocardiography
Intercellular Signaling Peptides and Proteins
Coronary Vessels
Myocardium
Down-Regulation

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. / Yao, Liang Tang; Zhao, Qiang; Qin, Xinyu; Shen, Leping; Cheng, Leilei; Ge, Junbo; Phillips, M. Ian.

In: Annals of Thoracic Surgery, Vol. 80, No. 1, 01.07.2005, p. 229-237.

Research output: Contribution to journalArticle

Yao, Liang Tang ; Zhao, Qiang ; Qin, Xinyu ; Shen, Leping ; Cheng, Leilei ; Ge, Junbo ; Phillips, M. Ian. / Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. In: Annals of Thoracic Surgery. 2005 ; Vol. 80, No. 1. pp. 229-237.
@article{c6acc0b86a584d81bd74cc3f500a3157,
title = "Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction",
abstract = "Background. There are several reports that engrafted mesenchymal stem cells (MSCs) stimulate angiogenesis in the ischemic heart, but the mechanism remains controversial. We hypothesize that transplantation of MSCs enhances vascular regeneration through a paracrine action. Methods. A transmural myocardial infarction was created by ligation of the left anterior descending coronary artery in rats. Those with an ejection fraction less than 0.70 1 week after myocardial infarction were included. Autologous MSCs (1 × 107; 0.2 mL) or culture medium (0.2 mL) was injected intramyocardially into the periinfarct zone (50 μL/injection at four sites; n = 20/group). At 2 weeks after transplantation, Western blot analysis was used to assay the paracrine factors and proapoptotic proteins. Echocardiography to assess heart function was performed on additional groups at 8 weeks after implantation. Results. The angiogenic factors basic fibroblast growth factor, vascular endothelial growth factor, and stem cell homing factor (stromal cell-derived factor -1α) increased in the MSC-treated hearts compared with medium-treated hearts. This was accompanied by a downregulation of proapoptotic protein Bax in ischemic myocardium. Similarly, capillary density increased about 40{\%} in MSC-treated hearts compared with medium-treated hearts (p = 0.001). Left ventricular contractility, indicated by fractional shortening, improved in MSC-treated hearts at 2 months after implantation (MSCs: 48.6{\%} ± 19.9{\%}; medium: 18.7{\%} ± 6.4{\%}; p = 0.004). Conclusions. Autologous MSC transplantation attenuates left ventricular remodeling and improves cardiac performance. The major mechanism appears to be paracrine action of the engrafted cells, increasing angiogenesis and cytoprotection.",
author = "Yao, {Liang Tang} and Qiang Zhao and Xinyu Qin and Leping Shen and Leilei Cheng and Junbo Ge and Phillips, {M. Ian}",
year = "2005",
month = "7",
day = "1",
doi = "10.1016/j.athoracsur.2005.02.072",
language = "English (US)",
volume = "80",
pages = "229--237",
journal = "Annals of Thoracic Surgery",
issn = "0003-4975",
publisher = "Elsevier USA",
number = "1",

}

TY - JOUR

T1 - Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction

AU - Yao, Liang Tang

AU - Zhao, Qiang

AU - Qin, Xinyu

AU - Shen, Leping

AU - Cheng, Leilei

AU - Ge, Junbo

AU - Phillips, M. Ian

PY - 2005/7/1

Y1 - 2005/7/1

N2 - Background. There are several reports that engrafted mesenchymal stem cells (MSCs) stimulate angiogenesis in the ischemic heart, but the mechanism remains controversial. We hypothesize that transplantation of MSCs enhances vascular regeneration through a paracrine action. Methods. A transmural myocardial infarction was created by ligation of the left anterior descending coronary artery in rats. Those with an ejection fraction less than 0.70 1 week after myocardial infarction were included. Autologous MSCs (1 × 107; 0.2 mL) or culture medium (0.2 mL) was injected intramyocardially into the periinfarct zone (50 μL/injection at four sites; n = 20/group). At 2 weeks after transplantation, Western blot analysis was used to assay the paracrine factors and proapoptotic proteins. Echocardiography to assess heart function was performed on additional groups at 8 weeks after implantation. Results. The angiogenic factors basic fibroblast growth factor, vascular endothelial growth factor, and stem cell homing factor (stromal cell-derived factor -1α) increased in the MSC-treated hearts compared with medium-treated hearts. This was accompanied by a downregulation of proapoptotic protein Bax in ischemic myocardium. Similarly, capillary density increased about 40% in MSC-treated hearts compared with medium-treated hearts (p = 0.001). Left ventricular contractility, indicated by fractional shortening, improved in MSC-treated hearts at 2 months after implantation (MSCs: 48.6% ± 19.9%; medium: 18.7% ± 6.4%; p = 0.004). Conclusions. Autologous MSC transplantation attenuates left ventricular remodeling and improves cardiac performance. The major mechanism appears to be paracrine action of the engrafted cells, increasing angiogenesis and cytoprotection.

AB - Background. There are several reports that engrafted mesenchymal stem cells (MSCs) stimulate angiogenesis in the ischemic heart, but the mechanism remains controversial. We hypothesize that transplantation of MSCs enhances vascular regeneration through a paracrine action. Methods. A transmural myocardial infarction was created by ligation of the left anterior descending coronary artery in rats. Those with an ejection fraction less than 0.70 1 week after myocardial infarction were included. Autologous MSCs (1 × 107; 0.2 mL) or culture medium (0.2 mL) was injected intramyocardially into the periinfarct zone (50 μL/injection at four sites; n = 20/group). At 2 weeks after transplantation, Western blot analysis was used to assay the paracrine factors and proapoptotic proteins. Echocardiography to assess heart function was performed on additional groups at 8 weeks after implantation. Results. The angiogenic factors basic fibroblast growth factor, vascular endothelial growth factor, and stem cell homing factor (stromal cell-derived factor -1α) increased in the MSC-treated hearts compared with medium-treated hearts. This was accompanied by a downregulation of proapoptotic protein Bax in ischemic myocardium. Similarly, capillary density increased about 40% in MSC-treated hearts compared with medium-treated hearts (p = 0.001). Left ventricular contractility, indicated by fractional shortening, improved in MSC-treated hearts at 2 months after implantation (MSCs: 48.6% ± 19.9%; medium: 18.7% ± 6.4%; p = 0.004). Conclusions. Autologous MSC transplantation attenuates left ventricular remodeling and improves cardiac performance. The major mechanism appears to be paracrine action of the engrafted cells, increasing angiogenesis and cytoprotection.

UR - http://www.scopus.com/inward/record.url?scp=20544450374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20544450374&partnerID=8YFLogxK

U2 - 10.1016/j.athoracsur.2005.02.072

DO - 10.1016/j.athoracsur.2005.02.072

M3 - Article

C2 - 15975372

AN - SCOPUS:20544450374

VL - 80

SP - 229

EP - 237

JO - Annals of Thoracic Surgery

JF - Annals of Thoracic Surgery

SN - 0003-4975

IS - 1

ER -