title: Intramuscular delivery of 3D aggregates of HUVECs and cbMSCs for cellular cardiomyoplasty in rats with myocardial infarction.
abstract: Cell-based therapeutic neovascularization is a promising method for treating ischemic disorders. In this work, human umbilical vein endothelial cells (HUVECs) were thoroughly premixed with cord-blood mesenchymal stem cells (cbMSCs) and cultivated to form three-dimensional (3D) cell aggregates for cellular cardiomyoplasty. In the in vitro study, tubular networks were formed at day 1 after the co-culturing of dissociated HUVECs and cbMSCs on Matrigel; however, as time progressed, the grown tubular networks regressed severely. Conversely, when 3D cell aggregates were grown on Matrigel, mature and stable tubular networks were observed over time, under the influence of their intensive cell-extracellular matrix (ECM) interactions and cell-cell contacts. 3D cell aggregates were transplanted into the peri-infarct zones of rats with myocardial infarction (MI) via direct intramyocardial injection. Based on our pinhole single photon emission computed tomography (SPECT) myocardial-perfusion observations, echocardiographic heart-function examinations and histological analyses, the engrafted 3D cell aggregates considerably enhanced the vascular densities and the blood flow recovery in the ischemic myocardium over those of their dissociated counterparts, thereby reducing the size of perfusion defects and restoring cardiac function. These results demonstrate that the intramuscular delivery of 3D cell aggregates of HUVECs/cbMSCs can be a valuable cell-based regenerative therapeutic strategy against MI.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC; Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Ding-Yuan
authors.initials: DY
authors.lastname: Chen
authors.forename: Hao-Ji
authors.initials: HJ
authors.lastname: Wei
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Lin
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.forename: Chieh-Cheng
authors.initials: CC
authors.lastname: Huang
authors.forename: Cheng-Tse
authors.initials: CT
authors.lastname: Wu
authors.forename: Shiaw-Min
authors.initials: SM
authors.lastname: Hwang
authors.forename: Yen
authors.initials: Y
authors.lastname: Chang
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Sung
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D018421:Cardiomyoplasty / Q000379:methods*; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology; D004338:Drug Combinations; D006321:Heart / Q000503:physiopathology; D061307:Human Umbilical Vein Endothelial Cells / Q000637:transplantation*; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic; D011509:Proteoglycans / Q000737:chemistry; D051381:Rats; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen
keywords: Cell delivery; Cell-based therapy; Myocardial infarction; Neovascularization; Tissue engineering