Galectin-1-secreting neural stem cells elicit long-term neuroprotection against ischemic brain injury

• Published in: Scientific reports Vol. 5; no. 1; p. 9621
• Main Authors: Wang, Jiayin, Xia, Jinchao, Zhang, Feng, Shi, Yejie, Wu, Yun, Pu, Hongjian, Liou, Anthony K. F., Leak, Rehana K., Yu, Xinguang, Chen, Ling, Chen, Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.04.2015; Nature Publishing Group
• Subjects: 13; 13/1; 13/107; 13/21; 13/51; 631/378/1687; 631/378/1689/534; 64; 64/60; 82; 96; Animals; Behavior, Animal; Brain injury; Brain Ischemia - immunology; Brain Ischemia - metabolism; Brain Ischemia - pathology; Brain Ischemia - therapy; CD16 antigen; Cell Survival; Cerebral blood flow; Cerebral Infarction - pathology; Cerebral Infarction - therapy; Cognitive ability; Corpus Callosum - pathology; Corpus Striatum - pathology; Cytokines; Cytokines - biosynthesis; Galectin 1 - secretion; Galectin-1; Humanities and Social Sciences; Inflammation; Interleukin 10; Ischemia; Lipopolysaccharides; Macrophages; Macrophages - metabolism; Mice; Microglia; Microglia - metabolism; multidisciplinary; Neostriatum; Neural stem cells; Neural Stem Cells - metabolism; Neuroprotection; Nitric oxide; Nitric Oxide - metabolism; Phagocytosis; Phenotype; Polarization; Psychomotor Performance; Rodents; Science; Sensorimotor system; Stem Cell Transplantation; Stem cells; Stroke; Substantia alba; Time Factors; Transplantation; Traumatic brain injury; Tumor necrosis factor; White Matter - pathology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep09621

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.