Systemic transplantation of human adipose stem cells attenuated cerebral inflammation and degeneration in a hemorrhagic stroke model.
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.
Kim
Jeong-Min
JM
Stroke and Stem Cell Laboratory in the Clinical Research Institute, Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
Lee
Soon-Tae
ST
Chu
Kon
K
Jung
Keun-Hwa
KH
Song
Eun-Cheol
EC
Kim
Se-Jeong
SJ
Sinn
Dong-In
DI
Kim
Jin-Hee
JH
Park
Dong-Kyu
DK
Kang
Kyung-Mook
KM
Hyung Hong
Nan
N
Park
Hee-Kwon
HK
Won
Chong-Hyun
CH
Kim
Kyu-Han
KH
Kim
Manho
M
Kun Lee
Sang
S
Roh
Jae-Kyu
JK
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*