Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling.

Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Research Abstract Details 

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Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Abstract Text:

Lepeng Zeng,Qingsong Hu,Xiaohong Wang,Abdul Mansoor,Joseph Lee,Julia Feygin,Ge Zhang,Piradeep Suntharalingam,Sherry Boozer,Abner Mhashilkar,Carmelo J Panetta,Cory Swingen,Robert Deans,Arthur H L From,Robert J Bache,Catherine M Verfaillie,Jianyi Zhang,

BACKGROUND: The present study examined whether transplantation of adherent bone marrow-derived stem cells, termed pMultistem, induces neovascularization and cardiomyocyte regeneration that stabilizes bioenergetic and contractile function in the infarct zone and border zone (BZ) after coronary artery occlusion. METHODS AND RESULTS: Permanent left anterior descending artery occlusion in swine caused left ventricular remodeling with a decrease of ejection fraction from 55+/-5.6% to 30+/-5.4% (magnetic resonance imaging). Four weeks after left anterior descending artery occlusion, BZ myocardium demonstrated profound bioenergetic abnormalities, with a marked decrease in subendocardial phosphocreatine/ATP (31P magnetic resonance spectroscopy; 1.06+/-0.30 in infarcted hearts [n=9] versus 1.90+/-0.15 in normal hearts [n=8; P<0.01]). This abnormality was significantly improved by transplantation of allogeneic pMultistem cells (subendocardial phosphocreatine/ATP to 1.34+/-0.29; n=7; P<0.05). The BZ protein expression of creatine kinase-mt and creatine kinase-m isoforms was significantly reduced in infarcted hearts but recovered significantly in response to cell transplantation. MRI demonstrated that the infarct zone systolic thickening fraction improved significantly from systolic "bulging" in untreated animals with myocardial infarction to active thickening (19.7+/-9.8%, P<0.01), whereas the left ventricular ejection fraction improved to 42.0+/-6.5% (P<0.05 versus myocardial infarction). Only 0.35+/-0.05% donor cells could be detected 4 weeks after left anterior descending artery ligation, independent of cell transplantation with or without immunosuppression with cyclosporine A (with cyclosporine A, n=6; no cyclosporine A, n=7). The fraction of grafted cells that acquired an endothelial or cardiomyocyte phenotype was 3% and approximately 2%, respectively. Patchy spared myocytes in the infarct zone were found only in pMultistem transplanted hearts. Vascular density was significantly higher in both BZ and infarct zone of cell-treated hearts than in untreated myocardial infarction hearts (P<0.05). CONCLUSIONS: Thus, allogeneic pMultistem improved BZ energetics, regional contractile performance, and global left ventricular ejection fraction. These improvements may have resulted from paracrine effects that include increased vascular density in the BZ and spared myocytes in the infarct zone.

Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Publishing Authors By Initials

L Zeng,Q Hu,X Wang,A Mansoor,J Lee,J Feygin,G Zhang,P Suntharalingam,S Boozer,A Mhashilkar,CJ Panetta,C Swingen,R Deans,AH From,RJ Bache,CM Verfaillie,J Zhang,

For similar circulatory and respiratory physiology: cardiovascular physiology: cardiovascular physiologic processes: ventricular function: ventricular remodeling research abstracts see: circulatory and respiratory physiology: cardiovascular physiology: cardiovascular physiologic processes: ventricular function: ventricular remodeling research

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Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Circulation

VOLUME: 115

Page Numbers: 1866-75

Journal Abbreviation:

ISSN: 1524-4539

DAY: 26

MONTH: 03

YEAR: 2007

Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 147763

Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Keywords Mesh Terms:

KEYWORDS: Ventricular Remodeling

MESH TERMS: analysis

Chemical & Substance for Abstract: Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling. Information

Substance Name: Phosphocreatine

Registry Number: 67-07-2

Grant and Affiliation Information for Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodeling.

AFFILIATION: Department of Medicine, University of Minnesota Medical School, Minneapolis, Minn, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL71970

ACRONYM: HL

MEDLINETA: Circulation

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