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Exosome-Based Cell Homing and Angiogenic Differentiation for Dental Pulp Regeneration
Authors:Venkateswaran Ganesh  Dongrim Seol  Piedad C. Gomez-Contreras  Henry L. Keen  Kyungsup Shin  James A. Martin
Affiliation:1.Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA;2.Department of Roy J. Carver Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA;3.Department of Orthodontics, University of Iowa, Iowa City, IA 52242, USA;4.Iowa Institute of Human Genetics, University of Iowa, Iowa City, IA 52242, USA
Abstract:Exosomes have attracted attention due to their ability to promote intercellular communication leading to enhanced cell recruitment, lineage-specific differentiation, and tissue regeneration. The object of this study was to determine the effect of exosomes on cell homing and angiogenic differentiation for pulp regeneration. Exosomes (DPSC-Exos) were isolated from rabbit dental pulp stem cells cultured under a growth (Exo-G) or angiogenic differentiation (Exo-A) condition. The characterization of exosomes was confirmed by nanoparticle tracking analysis and an antibody array. DPSC-Exos significantly promoted cell proliferation and migration when treated with 5 × 108/mL exosomes. In gene expression analysis, DPSC-Exos enhanced the expression of angiogenic markers including vascular endothelial growth factor A (VEGFA), Fms-related tyrosine kinase 1 (FLT1), and platelet and endothelial cell adhesion molecule 1 (PECAM1). Moreover, we identified key exosomal microRNAs in Exo-A for cell homing and angiogenesis. In conclusion, the exosome-based cell homing and angiogenic differentiation strategy has significant therapeutic potential for pulp regeneration.
Keywords:pulp regeneration   dental pulp stem cells   exosomes   angiogenesis   cell homing   microRNA profile
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