title: Comparison of administration routes for adipose-derived stem cells in the treatment of middle cerebral artery occlusion in rats.
abstract: Given that adult adipose tissue is an abundant, accessible and safe source of stem cells, the use of adipose-derived stem cells (ADSCs) provides a promising approach in ischemic stroke. The delivery route, however, for transplantation of ADSCs in clinical application remains controversial regarding the time window, cell type, safety issues, 'first pass' effect and therapeutic effect. To determine the optimal administration route in transplantation of ADSCs, we compared the therapeutic effect of the three mainly used administration routes of ADSCs in a middle cerebral artery occlusion (MCAO) rat model. Cells isolated from the adipose tissue of adult rodents were differentiated and characterized in vitro, and further transplanted in vivo by intravenous, intra-arterial or intra-ventricular delivery. The infarct volume, expression of neurotrophic factors and the neurobehavioral improvements were evaluated after the equal dose of BrdU labeled ADSCs transplantation. Our results indicated that the equal dose of ADSCs delivered intravenously were effective in improving the neurological outcome and reducing the infarct volume after ischemic brain injury in long term duration in contrast to intra-arterial and intra-ventricular delivery. At 1-7 days after transplantation, the increased expression levels of BDNF, VEGF, bFGF, Bcl-2, IL-10 and decreased levels of caspase-3 and TNF-α in the intra-ventricular and intra-arterial groups were significant in contrast to the intravenous group. There was no significant difference among the three groups after 7 days. Our findings suggest that compared with the intra-ventricular delivery, intravascular injection allows higher dose injection with fewer invasions and appears to be optimal in application with regard to therapeutic efficacy, safety and feasibility.
authors: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha 410008, Hunan Province, China; Department of Neurosurgery, The First Teaching Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China.
authors: Guojia
authors: G
authors: Du
authors: Department of Rehabilitation, The Second Affiliated Hospital of Kunming Medical University, Kunming 650000, Yunan, China.
authors: Yao
authors: Y
authors: Liu
authors: Department of Neurosurgery, The First Teaching Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China. Electronic address: damrjab@163.com.
authors: Muren
authors: M
authors: Dang
authors: Department of Neurosurgery, The First Teaching Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China.
authors: Guohua
authors: G
authors: Zhu
authors: Department of Neurosurgery, The First Teaching Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China.
authors: Riqing
authors: R
authors: Su
authors: Department of Neurosurgery, The First Teaching Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China.
authors: Yandong
authors: Y
authors: Fan
authors: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha 410008, Hunan Province, China.
authors: Zeming
authors: Z
authors: Tan
authors: Department of Neurology, Guang Dong Hospital of Chinese Traditional Medicine, China.
authors: Li Xin
authors: LX
authors: Wang
authors: Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha 410008, Hunan Province, China. Electronic address: fangjiashengxy@163.com.
authors: Jiasheng
authors: J
authors: Fang
mesh_terms: D050156:Adipogenesis; D061605:Administration, Intravenous; D053687:Adult Stem Cells / Q000637:transplantation*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D048430:Cell Shape; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000628:therapy*; D007269:Injections, Intra-Arterial; D007276:Injections, Intraventricular; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D050151:Subcutaneous Fat / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D016222:Fibroblast Growth Factor 2; D016753:Interleukin-10
keywords: Adipose-derived stem cells; Delivery route; Ischemic stroke; Middle cerebral artery occlusion; Rat