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.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by deposits of extracellular -amyloid (A ) plaques, intracellular neurofibrillary tangles, and deficits in the cholinergic system [1]
The present study transplanted EGFP-transfected Human amniotic epithelial cells (HAECs) into the lateral ventricle of double transgenic mice that co-expressed mutant APPswe and PS1ΔE9 genes to determine if transplantation improved cognitive functions
The transgenic mice expressed a mutant form of human FAD variant of presenilin 1 (PS1) E9 and a chimeric mouse/human amyloid precursor protein APPswe
Summary
APPswe/PS1 E9 founder mice were obtained from Nanjing Institute of Experimental Model Animal and were bred in a heterozygote colony by pairing transgenic mice with normal wild-type (WT) littermates (C57BL6/J). The transgenic mice expressed a mutant form of human FAD variant of PS1 E9 (deletion of exon 9) and a chimeric mouse/human amyloid precursor protein APPswe (mouse APP695 harboring a human A domain and mutations K595N and M596L linked to Swedish FAD kindred). The mice were allowed free access to food and water and were housed in a 12 h dark-light cycle. All experiments were performed during the light phase of the circadian cycle. The PS1 E9 transgenic mice and mutant APPswe transgenic mice were crossbred to generate hemizygous offspring with four possible genotypes: nontransgenic (wild-type); PS1 E9 transgenic; APPswe transgenic and double-transgenic APPswe+PS1ΔE9. The transplantation group was treated with EGFP-transfected HAECs, and the control group with an equal amount of PBS
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