title: Synergy of endothelial and neural progenitor cells from adipose-derived stem cells to preserve neurovascular structures in rat hypoxic-ischemic brain injury.
abstract: Perinatal cerebral hypoxic-ischemic (HI) injury damages the architecture of neurovascular units (NVUs) and results in neurological disorders. Here, we differentiated adipose-derived stem cells (ASCs) toward the progenitor of endothelial progenitor cells (EPCs) and neural precursor cells (NPCs) via microenvironmental induction and investigated the protective effect by transplanting ASCs, EPCs, NPCs, or a combination of EPCs and NPCs (E+N) into neonatal HI injured rat pups. The E+N combination produced significant reduction in brain damage and cell apoptosis and the most comprehensive restoration in NVUs regarding neuron number, normal astrocytes, and vessel density. Improvements in cognitive and motor functions were also achieved in injured rats with E+N therapy. Synergistic interactions to facilitate transmigration under in vitro hypoxic microenvironment were discovered with involvement of the neuropilin-1 (NRP1) signal in EPCs and the C-X-C chemokine receptor 4 (CXCR4) and fibroblast growth factor receptor 1 (FGFR1) signals in NPCs. Therefore, ASCs exhibit great potential for cell sources in endothelial and neural lineages to prevent brain from HI damage.
authors.affiliation: Division of Plastic Surgery, National Cheng Kung University Hospital, North District, Tainan City, Taiwan.|Institute of Clinical Medicine, National Cheng Kung University, North District, Tainan City, Taiwan.
authors.forename: Yuan-Yu
authors.initials: YY
authors.lastname: Hsueh
authors.affiliation: Department of Cell Biology and Anatomy, National Cheng Kung University, North District, Tainan City, Taiwan.|Institute of Basic Medical Sciences, National Cheng Kung University, North District, Tainan City, Taiwan.
authors.forename: Ya-Ju
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, North District, Tainan City, Taiwan.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Department of Cell Biology and Anatomy, National Cheng Kung University, North District, Tainan City, Taiwan.
authors.forename: Fitri
authors.initials: F
authors.lastname: Handayani
authors.affiliation: Department of Cell Biology and Anatomy, National Cheng Kung University, North District, Tainan City, Taiwan.|Institute of Basic Medical Sciences, National Cheng Kung University, North District, Tainan City, Taiwan.
authors.forename: Yi-Lun
authors.initials: YL
authors.lastname: Chiang
authors.affiliation: Department of Occupational Therapy, I-Shou University, Kaohsiung City, Taiwan.
authors.forename: Shih-Chen
authors.initials: SC
authors.lastname: Fan
authors.affiliation: Institute of Clinical Medicine, National Cheng Kung University, North District, Tainan City, Taiwan.|Department of Pediatrics, Taipei Medical University, Xinyi District, Taipei City, Taiwan.
authors.forename: Chien-Jung
authors.initials: CJ
authors.lastname: Ho
authors.affiliation: Department of Cell Biology and Anatomy, National Cheng Kung University, North District, Tainan City, Taiwan.|Institute of Basic Medical Sciences, National Cheng Kung University, North District, Tainan City, Taiwan.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Kuo
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, North District, Tainan City, Taiwan.|Department of Physiology, National Cheng Kung University, North District, Tainan City, Taiwan.
authors.forename: Shang-Hsun
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Institute of Oral Medicine, National Cheng Kung University, North District, Tainan City, Taiwan.
authors.forename: Yuh-Ling
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Division of Plastic Surgery, National Cheng Kung University Hospital, North District, Tainan City, Taiwan.
authors.forename: Sheng-Che
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Institute of Clinical Medicine, National Cheng Kung University, North District, Tainan City, Taiwan.|Department of Pediatrics, Taipei Medical University, Xinyi District, Taipei City, Taiwan.|Department of Pediatrics, Wan-fan Hospital, College of Medicine, Taipei Medical University, Xinyi District, Taipei City, Taiwan.
authors.forename: Chao-Ching
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Cell Biology and Anatomy, National Cheng Kung University, North District, Tainan City, Taiwan.|Institute of Basic Medical Sciences, National Cheng Kung University, North District, Tainan City, Taiwan.|Department of Biomedical Engineering, National Cheng Kung University, North District, Tainan City, Taiwan.|Medical Device Innovation Center, National Cheng Kung University, North District, Tainan City, Taiwan.
authors.forename: Chia-Ching
authors.initials: CC
authors.lastname: Wu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000831:Animals, Newborn; D001808:Blood Vessels / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D066026:Endothelial Progenitor Cells / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D039942:Neuropilin-1 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4; D039942:Neuropilin-1