title: Modulation of human mesenchymal stem cell function in a three-dimensional matrix promotes attenuation of adverse remodelling after myocardial infarction.
abstract: The application of tissue engineering (TE) practices for cell delivery offers a unique approach to cellular cardiomyoplasty. We hypothesized that human mesenchymal stem cells (hMSCs) applied to the heart in a collagen matrix would outperform the same cells grown in a monolayer and directly injected for cardiac cell replacement after myocardial infarction in a rat model. When hMSC patches were transplanted to infarcted hearts, several measures for left ventricle (LV) remodelling and function were improved, including fractional area change, wall thickness, -dP/dt and LV end-diastolic pressure. Neovessel formation throughout the LV infarct wall after hMSC patch treatment increased by 37% when compared to direct injection of hMSCs. This observation was correlated with increased secretion of angiogenic factors, with accompanying evidence that these factors enhanced vessel formation (30% increase) and endothelial cell growth (48% increase) in vitro. These observations may explain the in vivo observations of increased vessel formation and improved cardiac function with patch-mediated cell delivery. Although culture of hMSC in collagen patches enhanced angiogenic responses, there was no effect on cell potency or viability. Therefore, hMSCs delivered as a cardiac patch showed benefits above those derived from monolayers and directly injected. hMSCs cultured and delivered within TE constructs may represent a good option to maximize the effects of cellular cardiomyoplasty.
authors.affiliation: University of Illinois at Chicago, IL 60612, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Simpson
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Dudley
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology; D002450:Cell Communication / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006334:Heart Function Tests; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D051381:Rats; D011923:Rats, Nude; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned; D003094:Collagen