title: Therapeutic effects of human amniotic epithelial cell transplantation on double-transgenic mice co-expressing APPswe and PS1ΔE9-deleted genes.
abstract: Human amniotic epithelial cells (HAECs), which exhibit characteristics of embryonic and pluripotent stem cells, could be utilized for cell therapy without legal or ethical problems. Double-transgenic (TG) mice (n=20) and wild-type (WT) mice (n=20) were randomly assigned to two groups, respectively. The transplantation group was treated with HAECs and the control group with PBS. A six-radial arm water maze was used to assess spatial memory. Immunofluorescence was utilized to track HAEC survival. Immunohistochemistry was used to determine octamer-binding protein 4 (oct-4) and nanog expression in the HAECs. High-performance liquid chromatography (HPLC) was used to measure acetylcholine levels in the hippocampus. The density of cholinergic neurons in the basal forebrain and nerve fibers in the hippocampus was measured following acetylcholinesterase staining. Results showed that transplanted HAECs survived for at least eight weeks and migrated to the third ventricle without immune rejection. Graft HAECs also expressed the specific stem cell markers oct-4 and nanog. Compared with the control group, HAEC transplantation significantly ameliorated spatial memory deficits in TG mice, as well as increased acetylcholine levels and the number of hippocampal cholinergic neurites. Intracerebroventricular HAEC transplantation improved spatial memory in double-TG mice, and results suggested that increased acetylcholine levels in the hippocampus, released by surviving cholinergic neurites, were responsible for this improvement.
authors.affiliation: Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Shouru
authors.initials: S
authors.lastname: Xue
authors.forename: Chongfang
authors.initials: C
authors.lastname: Chen
authors.forename: Wanli
authors.initials: W
authors.lastname: Dong
authors.forename: Guozhen
authors.initials: G
authors.lastname: Hui
authors.forename: Tianjun
authors.initials: T
authors.lastname: Liu
authors.forename: Lihe
authors.initials: L
authors.lastname: Guo
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D000650:Amnion / Q000166:cytology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D059329:Cholinergic Neurons / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D017353:Gene Deletion; D006085:Graft Survival / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D016564:Amyloid beta-Protein Precursor; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D053764:Presenilin-1; D000109:Acetylcholine