Multimodality noninvasive imaging for assessing therapeutic effects of exogenously transplanted cell aggregates capable of angiogenesis on acute myocardial infarction

• Published in: Biomaterials 2015-12, Vol.73, p.12-22
• Main Authors: Huang, Chieh-Cheng, Wei, Hao-Ji, Lin, Kun-Ju, Lin, Wei-Wen, Wang, Ching-Wen, Pan, Wen-Yu, Hwang, Shiaw-Min, Chang, Yen, Sung, Hsing-Wen
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Aggregates; angiogenesis; Animals; Blood; cardiac output; cell aggregates; Cell-based therapy; Cellular cardiomyoplasty; Collagen - chemistry; computed tomography; Correlation; Dentistry; Drug Combinations; Echocardiography; Heart Ventricles - pathology; Human Umbilical Vein Endothelial Cells; Humans; hydrocolloids; Hydrogels - chemistry; image analysis; Integrin alphaVbeta3 - metabolism; integrins; Ischemic diseases; Laminin - chemistry; Mathematical analysis; Mathematical models; Mesenchymal Stem Cell Transplantation; methylcellulose; Methylcellulose - chemistry; Multimodal Imaging - methods; Myocardial infarction; Myocardial Infarction - therapy; Neovascularization, Pathologic; Neovascularization, Physiologic; Perfusion; photons; Positron-Emission Tomography; Proteoglycans - chemistry; Rats; Rats, Inbred Lew; stem cells; therapeutics; Three dimensional; Tomography; Tomography, Emission-Computed, Single-Photon; Translational medicine; Vasculogenesis
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2015.09.009

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 αv β3 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.