title: Systemic transplantation of human adipose stem cells attenuated cerebral inflammation and degeneration in a hemorrhagic stroke model.
abstract: Adipose-derived stem cells (ASCs) are readily accessible multipotent mesenchymal stem cells and are known to secrete multiple growth factors, and thereby to have cytoprotective effects in various injury models. In the present study, the authors investigated the neuroprotective effect of ASCs in an intracerebral hemorrhage (ICH) model. ICH was induced via the stereotaxic infusion of collagenase, and human ASCs (three million cells per animal) isolated from human fresh fat tissue, were intravenously administered at 24 h post-ICH induction. Acute brain inflammation markers, namely, cell numbers positively stained for terminal transferase dUTP nick end labeling (TUNEL), myeloperoxidase (MPO), or OX-42, and brain water content were checked at 3 days post-ICH. In addition, the authors quantified brain degeneration by measuring hemispheric atrophy and perihematomal glial thickness at 6 weeks post-ICH, and determined modified limb placing behavioral scores weekly over 5 weeks post-ICH. The results showed that brain water content, TUNEL+, and MPO+ cell numbers were significantly reduced in the ASC-transplanted rats. ASC transplantation attenuated neurological deficits from 4 to 5 weeks post-ICH, and reduced both the brain atrophy and the glial proliferation at 6 weeks. Transplanted ASCs were found to densely populate perihematomal areas at 6 weeks, and to express endothelial markers (von Willebrand factor and endothelial barrier antigen), but not neuronal or glial markers. In summary, ASCs transplantation in the ICH model reduced both acute cerebral inflammation and chronic brain degeneration, and promoted long-term functional recovery.
authors.affiliation: Stroke and Stem Cell Laboratory in the Clinical Research Institute, Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Song
authors.forename: Se-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Dong-In
authors.initials: DI
authors.lastname: Sinn
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Park
authors.forename: Kyung-Mook
authors.initials: KM
authors.lastname: Kang
authors.forename: Nan
authors.initials: N
authors.lastname: Hyung Hong
authors.forename: Hee-Kwon
authors.initials: HK
authors.lastname: Park
authors.forename: Chong-Hyun
authors.initials: CH
authors.lastname: Won
authors.forename: Kyu-Han
authors.initials: KH
authors.lastname: Kim
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Sang
authors.initials: S
authors.lastname: Kun Lee
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
mesh_terms: D017667:Adipocytes / Q000637:transplantation*; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D001284:Atrophy; D001519:Behavior / Q000502:physiology; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation / Q000502:physiology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000473:pathology* / Q000628:therapy*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000209:etiology / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology* / Q000628:therapy*; D009457:Neuroglia / Q000473:pathology; D020556:Neutrophil Infiltration / Q000502:physiology; D033581:Stem Cell Transplantation; D020521:Stroke / Q000209:etiology / Q000473:pathology* / Q000628:therapy*