title: Multimodality noninvasive imaging for assessing therapeutic effects of exogenously transplanted cell aggregates capable of angiogenesis on acute myocardial infarction.
abstract: Although the induction of neovascularization by cell-based approaches has demonstrated substantial potential in treating myocardial infarction (MI), the process of cell-mediated angiogenesis and its correlation with therapeutic mechanisms of cardiac repair remain elusive. In this work, three-dimensional (3D) aggregates of human umbilical vein endothelial cells (HUVECs) and cord-blood mesenchymal stem cells (cbMSCs) are constructed using a methylcellulose hydrogel system. By maximizing cell-cell and cell-ECM communications and establishing a hypoxic microenvironment in their inner cores, these cell aggregates are capable of forming widespread tubular networks together with the angiogenic marker αvβ3 integrin; they secret multiple pro-angiogenic, pro-survival, and mobilizing factors when grown on Matrigel. The aggregates of HUVECs/cbMSCs are exogenously engrafted into the peri-infarct zones of rats with MI via direct local injection. Multimodality noninvasive imaging techniques, including positron emission tomography, single photon emission computed tomography, and echocardiography, are employed to monitor serially the beneficial effects of cell therapy on angiogenesis, blood perfusion, and global/regional ventricular function, respectively. The myocardial perfusion is correlated with ventricular contractility, demonstrating that the recovery of blood perfusion helps to restore regional cardiac function, leading to the improvement in global ventricular performance. These experimental data reveal the efficacy of the exogenous transplantation of 3D cell aggregates after MI and elucidate the mechanism of cell-mediated therapeutic angiogenesis for cardiac repair.
authors.affiliation: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Chieh-Cheng
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Division of Cardiovascular Surgery, Veterans General Hospital-Taichung, and College of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Division of Cardiovascular Surgery, Chiayi Branch, Veterans General Hospital-Taichung, Chiayi, Taiwan, ROC.
authors.forename: Hao-Ji
authors.initials: HJ
authors.lastname: Wei
authors.affiliation: Healthy Aging Research Center, Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Department of Nuclear Medicine and Center of Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC.
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Veterans General Hospital-Taichung, Taichung, Taiwan, ROC; Department of Life Science, Tunghai University, Taichung, Taiwan, ROC.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Lin
authors.affiliation: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC; Division of Cardiovascular Surgery, Veterans General Hospital-Taichung, and College of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Pan
authors.affiliation: Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, ROC.
authors.forename: Shiaw-Min
authors.initials: SM
authors.lastname: Hwang
authors.affiliation: Division of Cardiovascular Surgery, Veterans General Hospital-Taichung, and College of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address: ychang@vghtc.gov.tw.
authors.forename: Yen
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC. Electronic address: hwsung@mx.nthu.edu.tw.
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Sung
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D004452:Echocardiography; D006352:Heart Ventricles / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007797:Laminin / Q000737:chemistry; D045164:Mesenchymal Stem Cell Transplantation; D008747:Methylcellulose / Q000737:chemistry; D064847:Multimodal Imaging / Q000379:methods*; D009203:Myocardial Infarction / Q000628:therapy*; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D010477:Perfusion; D049268:Positron-Emission Tomography; D011509:Proteoglycans / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D004338:Drug Combinations; D020100:Hydrogels; D039302:Integrin alphaVbeta3; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D008747:Methylcellulose; D003094:Collagen
keywords: Cell-based therapy; Cellular cardiomyoplasty; Ischemic diseases; Translational medicine; Vasculogenesis