Improvement of neurological deficits by intracerebral transplantation of human adipose tissue-derived stromal cells after cerebral ischemia in rats.
Mesenchymal stem cells can be expanded rapidly in vitro and differentiated into multiple mesodermal cell types. In addition, their differentiation into neuron-like cells expressing markers typical for mature neurons has been reported. We isolated human adipose tissue stromal cells (hATSCs) from human liposuction tissues and induced neural differentiation with azacytidine. Following neural induction, hATSCs changed toward neural morphology and displayed expression of MAP2 and GFAP. hATSCs, which were labeled with LacZ adenovirus, were injected into the lateral ventricle of the rat brain. Transplanted cells migrated to various parts of the brain, and ischemic brain injury by middle cerebral artery occlusion (MCAo) increased their migration to the injured cortex. Some of the transplanted cells expressed MAP2 and GFAP. Transplantation of hATSCs improved functional deficits in ischemic brain injury induced by MCAo. Intracerebral grafting of BDNF-transduced hATSCs significantly improved motor recovery of functional deficits in MCAo rats. These data indicate that transplanted hATSCs survive, migrate, and improve functional recovery after stroke and that genetically engineered hATSCs can express biologically active gene products and, therefore, can function as effective vehicles for therapeutic gene transfer to the brain.
Kang
Soo Kyung
SK
Department of Physiology, College of Medicine, Pusan National University, Pusan, South Korea.
Lee
Dong Hyung
DH
Bae
Yong Chan
YC
Kim
Hae Kyu
HK
Baik
Sun Yong
SY
Jung
Jin Sup
JS
D000256:Adenoviridae / Q000235:genetics; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001374:Azacitidine / Q000494:pharmacology; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006085:Graft Survival / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D020547:Lateral Ventricles / Q000473:pathology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D016896:Treatment Outcome
D000943:Antigens, Differentiation; D019208:Brain-Derived Neurotrophic Factor; D001374:Azacitidine