title: Galectin-1-secreting neural stem cells elicit long-term neuroprotection against ischemic brain injury.
abstract: Galectin-1 (gal-1), a special lectin with high affinity to β-galactosides, is implicated in protection against ischemic brain injury. The present study investigated transplantation of gal-1-secreting neural stem cell (s-NSC) into ischemic brains and identified the mechanisms underlying protection. To accomplish this goal, secretory gal-1 was stably overexpressed in NE-4C neural stem cells. Transient cerebral ischemia was induced in mice by middle cerebral artery occlusion for 60 minutes and s-NSCs were injected into the striatum and cortex within 2 hours post-ischemia. Brain infarct volume and neurological performance were assessed up to 28 days post-ischemia. s-NSC transplantation reduced infarct volume, improved sensorimotor and cognitive functions, and provided more robust neuroprotection than non-engineered NSCs or gal-1-overexpressing (but non-secreting) NSCs. White matter injury was also ameliorated in s-NSC-treated stroke mice. Gal-1 modulated microglial function in vitro, by attenuating secretion of pro-inflammatory cytokines (TNF-α and nitric oxide) in response to LPS stimulation and enhancing production of anti-inflammatory cytokines (IL-10 and TGF-β). Gal-1 also shifted microglia/macrophage polarization toward the beneficial M2 phenotype in vivo by reducing CD16 expression and increasing CD206 expression. In sum, s-NSC transplantation confers robust neuroprotection against cerebral ischemia, probably by alleviating white matter injury and modulating microglial/macrophage function.
authors: 1] Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [2] Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors: Jiayin
authors: J
authors: Wang
authors: 1] Cerebrovascular Center, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou 450003, China [2] Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors: Jinchao
authors: J
authors: Xia
authors: 1] Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA [2] Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA.
authors: Feng
authors: F
authors: Zhang
authors: 1] Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA [2] Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA.
authors: Yejie
authors: Y
authors: Shi
authors: 1] Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [2] Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors: Yun
authors: Y
authors: Wu
authors: 1] Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA [2] Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA.
authors: Hongjian
authors: H
authors: Pu
authors: Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors: Anthony K F
authors: AK
authors: Liou
authors: Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282, USA.
authors: Rehana K
authors: RK
authors: Leak
authors: Department of Neurosurgery and PLA Institute of Neurosurgery, Chinese PLA General Hospital, Beijing 100853, China.
authors: Xinguang
authors: X
authors: Yu
authors: Department of Neurosurgery and PLA Institute of Neurosurgery, Chinese PLA General Hospital, Beijing 100853, China.
authors: Ling
authors: L
authors: Chen
authors: 1] Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA [2] Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA.
authors: Jun
authors: J
authors: Chen
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002470:Cell Survival; D002544:Cerebral Infarction / Q000473:pathology / Q000628:therapy; D003337:Corpus Callosum / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D037483:Galectin 1 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis; D010641:Phenotype; D011597:Psychomotor Performance; D033581:Stem Cell Transplantation; D013997:Time Factors; D066127:White Matter / Q000473:pathology
chemical_list: D016207:Cytokines; D037483:Galectin 1; D009569:Nitric Oxide