1. Endothelial Progenitor Cell Secretome and Oligovascular Repair in a Mouse Model of Prolonged Cerebral Hypoperfusion
- Author
-
Anna Morancho, Pablo Martinez-San Segundo, Eng H. Lo, Takakuni Maki, Kazuo Washida, Hajime Takase, Ken Arai, Anna Rosell, Esperanza Medina-Gutiérrez, Anna C. Liang, Joan Montaner, Marina Gabriel-Salazar, Kazuhide Hayakawa, and Josephine Lok
- Subjects
0301 basic medicine ,Receptor, Platelet-Derived Growth Factor alpha ,Angiogenin ,In Vitro Techniques ,Vascular Remodeling ,Endothelial progenitor cell ,Article ,Brain Ischemia ,White matter ,03 medical and health sciences ,Myelin ,Mice ,0302 clinical medicine ,In vivo ,medicine ,Animals ,Humans ,Carotid Stenosis ,Progenitor cell ,Cell Proliferation ,Endothelial Progenitor Cells ,Advanced and Specialized Nursing ,Oligodendrocyte Precursor Cells ,business.industry ,Regeneration (biology) ,Myelin Basic Protein ,Ribonuclease, Pancreatic ,White Matter ,In vitro ,Cell biology ,Platelet Endothelial Cell Adhesion Molecule-1 ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Glutathione S-Transferase pi ,Culture Media, Conditioned ,embryonic structures ,cardiovascular system ,Cytokines ,Intercellular Signaling Peptides and Proteins ,Angiogenesis Inducing Agents ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,circulatory and respiratory physiology ,Peptide Hydrolases - Abstract
Background and Purpose— Endothelial progenitor cells (EPCs) have been extensively investigated as a therapeutic approach for repairing the vascular system in cerebrovascular diseases. Beyond vascular regeneration per se, EPCs may also release factors that affect the entire neurovascular unit. Here, we aim to study the effects of the EPC secretome on oligovascular remodeling in a mouse model of white matter injury after prolonged cerebral hypoperfusion. Methods— The secretome of mouse EPCs was analyzed with a proteome array. In vitro, the effects of the EPC secretome and its factor angiogenin were assessed on primary oligodendrocyte precursor cells and mature human cerebral microvascular endothelial cells (hCMED/D3). In vivo, mice were subjected to permanent bilateral common carotid artery stenosis, then treated with EPC secretome at 24 hours and at 1 week, and cognitive outcome was evaluated with the Y maze test together with oligodendrocyte precursor cell proliferation/differentiation and vascular density in white matter at 4 weeks. Results— Multiple growth factors, cytokines, and proteases were identified in the EPC secretome, including angiogenin. In vitro, the EPC secretome significantly enhanced endothelial and oligodendrocyte precursor cell proliferation and potentiated oligodendrocyte precursor cell maturation. Angiogenin was proved to be a key factor since pharmacological blockade of angiogenin signaling negated the positive effects of the EPC secretome. In vivo, treatment with the EPC secretome increased vascular density, myelin, and mature oligodendrocytes in white matter and rescued cognitive function in the mouse hypoperfusion model. Conclusions— Factors secreted by EPCs may ameliorate white matter damage in the brain by boosting oligovascular remodeling.
- Published
- 2017