Transplantation of Induced Pluripotent Stem Cells Alleviates Cerebral Inflammation and Neural Damage in Hemorrhagic Stroke

• Published in: PloS one 2015-06, Vol.10 (6), p.e0129881-e0129881
• Main Authors: Qin, Jie, Ma, Xun, Qi, Haiyun, Song, Bo, Wang, Yanlin, Wen, Xuejun, Wang, Qing Mei, Sun, Shilei, Li, Yusheng, Zhang, Rui, Liu, Xinjing, Hou, Haiman, Gong, Guangming, Xu, Yuming
• Format: Article
• Language: English
• Subjects: Analysis; Animal tissues; Animals; Apoptosis; Brain; Brain - cytology; Brain - immunology; Brain - pathology; Brain injury; Cell survival; Cerebral Hemorrhage - immunology; Cerebral Hemorrhage - pathology; Cerebral Hemorrhage - therapy; Clinical medicine; Collagen; Collagenase; Cytokines; Edema; Fibroblasts; Glial fibrillary acidic protein; Health aspects; Hemorrhage; Hospitals; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - transplantation; Inflammation; Inflammation - immunology; Inflammation - pathology; Inflammation - therapy; Inhibitory postsynaptic potentials; Injuries; Interleukin 10; Interleukin 6; Interleukins - analysis; Interleukins - immunology; Intermediate filament proteins; Ischemia; Laboratories; Leukocytes (neutrophilic); Male; Medicine; Microglia; Moisture content; Neostriatum; Neurobiology; Neurogenesis; Neurology; Neuromodulation; Neuronal-glial interactions; Neurons - cytology; Neurons - immunology; Neurons - pathology; Neuroprotection; Neurosciences; Pluripotency; Proteins; Rats; Rats, Sprague-Dawley; Recovery of function; Rodents; Stem cell transplantation; Stem cells; Stroke; Survival; Transplantation; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - immunology; Tumors; Water content
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0129881

Little is known about the effects of induced pluripotent stem cell (iPSC) treatment on acute cerebral inflammation and injuries after intracerebral hemorrhage (ICH), though they have shown promising therapeutic potentials in ischemic stoke. An ICH model was established by stereotactic injection of collagenase VII into the left striatum of male Sprague-Dawley (SD) rats. Six hours later, ICH rats were randomly divided into two groups and received intracerebrally 10 μl of PBS with or without 1 × 10(6) of iPSCs. Subsequently, neural function of all ICH rats was assessed at days 1, 3, 7, 14, 28 and 42 after ICH. Inflammatory cells, cytokines and neural apoptosis in the rats' perihematomal regions, and brain water content were determined on day 2 or 3 post ICH. iPSC differentiation was determined on day 28 post ICH. Nissl(+) cells and glial fibrillary acidic protein (GFAP)(+) cells in the perihematoma and the survival rates of rats in two groups were determined on post-ICH day 42. Compared with control animals, iPSCs treatment not only improved neurological function and survival rate, but also resulted in fewer intracephalic infiltrations of neutrophils and microglia, along with decreased interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α), and increased IL-10 in the perihematomal tissues of ICH rats. Furthermore, brain oedema formation, apoptosis, injured neurons and glial scar formation were decreased in iPSCs-transplanted rats. Our findings indicate that iPSCs transplantation attenuate cerebral inflammatory reactions and neural injuries after ICH, and suggests that multiple mechanisms including inflammation modulation, neuroprotection and functional recovery might be involved simultaneously in the therapeutic benefit of iPSC treatment against hemorrhagic stroke.