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Hepatocyte growth factor and granulocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy.
Cytotherapy. 2008; 10(8):857-67.C

Abstract

BACKGROUND

Myocardial infarction (MI) is a significant cause of heart failure. Current therapies are limited and, therefore, the development of novel revascularization methods is potentially important. We investigated whether hepatocyte growth factor (HGF), expressed by genetically modified mesenchymal stromal cells (MSC), in combination with granulocyte colony-stimulating factor (G-CSF), exhibited a synergistic therapeutic benefit, as measured 8 weeks after MI induction in a rat model.

METHODS

Four weeks after MI, rats were randomly divided into a control group (n=11), HGF group (Adenovirus vector carrying human HGF (Ad-HGF)-transfected MSC transplanted into the infarct zone; n=11), G-CSF group (intraperitoneal injection with G-CSF; n=11), and HGF + G-CSF group (Ad-HGF-transfected MSC transplanted into the infarct zone and intraperitoneal injection with G-CSF; n=11). Four weeks later, hearts were analyzed for endothelial cell density and angiogenesis, ventricular geometry, myocardial function and levels of VCAM-1 and MMP-9 protein.

RESULTS

The HGF + G-CSF group exhibited improved left ventricular systolic and diastolic function and experienced less adverse ventricular remodeling, as manifested by decreased left ventricular dilatation and increased border zone wall thickness. Angiogenesis was significantly enhanced in HGF + G-CSF rats by inducing the proliferation of endothelial cells. Furthermore, HGF induced expression of VCAM-1, and HGF treatment together with G-CSF synergistically stimulated MMP-9 expression in ischemic hearts.

DISCUSSION

The combination of G-CSF and HGF exhibited a significant synergistic effect and enhanced myocardial endothelial density, angiogenesis, geometric preservation and heart function in an ischemic cardiomyopathy model.

Authors+Show Affiliations

Department of Respiration, Chinese PLA General Hospital, Beijing, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18956268

Citation

Guo, Ying-Hua, et al. "Hepatocyte Growth Factor and Granulocyte Colony-stimulating Factor Form a Combined Neovasculogenic Therapy for Ischemic Cardiomyopathy." Cytotherapy, vol. 10, no. 8, 2008, pp. 857-67.
Guo YH, He JG, Wu JL, et al. Hepatocyte growth factor and granulocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy. Cytotherapy. 2008;10(8):857-67.
Guo, Y. H., He, J. G., Wu, J. L., Yang, L., Zhang, D. S., Tan, X. Y., & Qi, R. D. (2008). Hepatocyte growth factor and granulocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy. Cytotherapy, 10(8), 857-67. https://doi.org/10.1080/14653240802419278
Guo YH, et al. Hepatocyte Growth Factor and Granulocyte Colony-stimulating Factor Form a Combined Neovasculogenic Therapy for Ischemic Cardiomyopathy. Cytotherapy. 2008;10(8):857-67. PubMed PMID: 18956268.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatocyte growth factor and granulocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy. AU - Guo,Ying-Hua, AU - He,Jian-Guo, AU - Wu,Jun-Lou, AU - Yang,Long, AU - Zhang,Dong-Sheng, AU - Tan,Xiao-Yan, AU - Qi,Rui-Dong, PY - 2008/10/29/entrez PY - 2008/10/29/pubmed PY - 2009/7/18/medline SP - 857 EP - 67 JF - Cytotherapy JO - Cytotherapy VL - 10 IS - 8 N2 - BACKGROUND: Myocardial infarction (MI) is a significant cause of heart failure. Current therapies are limited and, therefore, the development of novel revascularization methods is potentially important. We investigated whether hepatocyte growth factor (HGF), expressed by genetically modified mesenchymal stromal cells (MSC), in combination with granulocyte colony-stimulating factor (G-CSF), exhibited a synergistic therapeutic benefit, as measured 8 weeks after MI induction in a rat model. METHODS: Four weeks after MI, rats were randomly divided into a control group (n=11), HGF group (Adenovirus vector carrying human HGF (Ad-HGF)-transfected MSC transplanted into the infarct zone; n=11), G-CSF group (intraperitoneal injection with G-CSF; n=11), and HGF + G-CSF group (Ad-HGF-transfected MSC transplanted into the infarct zone and intraperitoneal injection with G-CSF; n=11). Four weeks later, hearts were analyzed for endothelial cell density and angiogenesis, ventricular geometry, myocardial function and levels of VCAM-1 and MMP-9 protein. RESULTS: The HGF + G-CSF group exhibited improved left ventricular systolic and diastolic function and experienced less adverse ventricular remodeling, as manifested by decreased left ventricular dilatation and increased border zone wall thickness. Angiogenesis was significantly enhanced in HGF + G-CSF rats by inducing the proliferation of endothelial cells. Furthermore, HGF induced expression of VCAM-1, and HGF treatment together with G-CSF synergistically stimulated MMP-9 expression in ischemic hearts. DISCUSSION: The combination of G-CSF and HGF exhibited a significant synergistic effect and enhanced myocardial endothelial density, angiogenesis, geometric preservation and heart function in an ischemic cardiomyopathy model. SN - 1477-2566 UR - https://www.unboundmedicine.com/medline/citation/18956268/Hepatocyte_growth_factor_and_granulocyte_colony_stimulating_factor_form_a_combined_neovasculogenic_therapy_for_ischemic_cardiomyopathy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/904849728 DB - PRIME DP - Unbound Medicine ER -