title: Therapeutic effect of human adipose-derived stromal cells cluster in rat hind-limb ischemia.
abstract: We investigated whether transplantation of three-dimensional cell masses (3DCM) of human adipose-derived stromal cells (hASCs) cultured on a basic fibroblast growth factor-immobilized substrate improved hind limb functional recovery by stimulating angiogenesis in an immune-competent rat ischemic limb model. In vitro experiments confirmed that cells within 3DCMs differentiate toward the endothelial lineage one day after culture in normal medium. The therapeutic effect of 3DCMs was evaluated by transplanting hASCs, phosphate-buffered saline alone, and the 3DCM into rat ischemic hind limbs. Blood flow was enhanced in the ischemic hind limb in the 3DCM-injected group compared with the other groups. The ratio of human nuclear antigen (HNA) and hVEGF-positive cells was significantly higher in the 3DCM-injected group compared to hASC-injected group. Human VEGF was observed in most HNA-positive cells. Many hCD31 and hSMA-positive cells were observed in vessel-like structures in the 3DCM-injected group. The 3DCM transplantation improved cell retention and angiogenic effects compared with ASC transplantation. These findings suggest that transplantation of 3DCMs may be an effective stem cell therapy for hind limb ischemia.
authors: Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Korea.
authors: In-Su
authors: IS
authors: Park
authors: Jo A
authors: JA
authors: Kang
authors: Jungmi
authors: J
authors: Kang
authors: Jong-Won
authors: JW
authors: Rhie
authors: Sang-Heon
authors: SH
authors: Kim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005455:Fluorescent Antibody Technique; D006614:Hindlimb / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A
keywords: FGF2-immobilized substrate; adipose-derived stem cell; angiogenesis; endothelial differentiation; hypoxic induction; three-dimensional cell mass