title: Endothelial progenitor cells promote astrogliosis following spinal cord injury through Jagged1-dependent Notch signaling.
abstract: Interactions between endothelial and neural stem cells are believed to play a critical role in the kinetics of neural stem cells in the central nervous system. Here we demonstrate that endothelial progenitor cells promote the repair of injured spinal cord through the induction of Notch-dependent astrogliosis and vascular regulation. The transplantation of Jagged1(+/+) endothelial progenitor cells, but not Jagged1(-/-) endothelial progenitor cells, increased the number of reactive astrocytes during the acute phase, and improved functional recovery following spinal cord injury. Expression of the Notch effector Hes5 was upregulated in the injured spinal cord after Jagged1(+/+) endothelial progenitor cell transplantation. Furthermore, we found that the Notch ligand Delta-like-1 was highly expressed in Jagged1(-/-) endothelial progenitor cells. Transplantation of Delta-like-1, as well as Jagged1-overexpressing 3T3 cells, revealed that only Jagged1-overexpressing 3T3 stromal cells enhanced astrogliosis following spinal cord injury. In addition, Jagged1(+/+) endothelial progenitor cells exhibited not only dramatic pro-angiogenic effects, but also morphologically abnormal vessel stabilization, compared with Jagged1(-/-)endothelial progenitor cells in injured spinal cord. Thus, transplanted endothelial progenitor cells promote astrogliosis, vascular regulation, and spinal cord regeneration through activation of Jagged1-Notch signaling.
authors.affiliation: Group of Vascular Regeneration, Institute of Biomedical Research and Innovation, Hyogo, Japan.
authors.forename: Naosuke
authors.initials: N
authors.lastname: Kamei
authors.forename: Sang-Mo
authors.initials: SM
authors.lastname: Kwon
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ii
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Yamada
authors.forename: Katsuto
authors.initials: K
authors.lastname: Hozumi
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kawamoto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ochi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001369:Axons / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002465:Cell Movement; D017690:Cell Transplantation; D042783:Endothelial Cells / Q000502:physiology*; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D005911:Gliosis / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000502:physiology*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology; D013119:Spinal Cord Injuries / Q000473:pathology*
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins