title: Therapeutic effects of human adipose stem cell-conditioned medium on stroke.
abstract: Stem cell therapy is a promising approach for stroke. However, low survival rates and potential tumorigenicity of implanted cells could undermine the efficacy of the cell-based treatment. The use of stem cell-conditioned medium (CM) may be a feasible approach to overcome these limitations. Especially, specific stem cell culture condition and continuous infusion of CM into ischemic brains would have better therapeutic results. The CM was prepared by culturing human adipose-derived stem cells in a three-dimensional spheroid form to increase the secretion of angiogenic/neuroprotective factors. Ischemic stroke was induced by standard middle cerebral artery occlusion methods in the brain of 8-week-old Sprague-Dawley rats. Continuous infusion of CM or αMEM media (0.5 μl/hr) into the lateral ventricle was initiated 8 days after the surgery and maintained for 7 days. Alteration in the motor function was monitored by the rotarod test. Infarction volume and the number of microvessels or TUNEL-positive neural cells were analyzed 15 days after the surgery. Compared with αMEM, continuous CM infusion reduced the infarction volume and maintained motor function. The number of CD31-positive microvessels and TUNEL-positive neural cells significantly increased and decreased, respectively, in the penumbra regions. Although the apoptosis of all neural cell types decreased, reduction in the microglial apoptosis and astrogliosis was prominent and significant. In this study, the therapeutic effects of the CM against stroke were confirmed in an animal model. Increased endothelial cell proliferation, reduced neural cell apoptosis, and milder astrogliosis may play important roles in the treatment effects of CM.
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Cho
authors.forename: Hyeon Suk
authors.initials: HS
authors.lastname: Song
authors.forename: Sukho
authors.initials: S
authors.lastname: Bhang
authors.forename: Saehyoung
authors.initials: S
authors.lastname: Lee
authors.forename: Bong Gu
authors.initials: BG
authors.lastname: Kang
authors.forename: Jae Chul
authors.initials: JC
authors.lastname: Lee
authors.forename: Jaeyeol
authors.initials: J
authors.lastname: An
authors.forename: Choong Ik
authors.initials: CI
authors.lastname: Cha
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Kyeung Min
authors.initials: KM
authors.lastname: Joo
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D018613:Microscopy, Confocal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism*; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
chemical_list: D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned