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.Alzheimer's disease, human amniotic epithelial cells, spatial memory deficit, transgenic mice Citation:Xue S R, Chen C F, Dong W L, et al. Therapeutic effects of human amniotic epithelial cell transplantation on double-transgenic mice co-expressing APPswe and PS1E9-deleted genes.

Therapeutic potential of human amniotic membrane-derived mesenchymal stem cells in APP transgenic mice

“…Our findings demonstrated that cognitive function improved significantly as the Aβ level decreased. Intracerebroventricular transplantation of hAMMSCs increased acetylcholine concentration and the number of hippocampal cholinergic neurites in AbPP/PS1 transgenic AD mice (34). Following hAMMSC injection, the number of ED1-positive phagocytic microglial cells associated with Aβ plaques was enhanced, the expression levels of proinflammatory cytokines were decreased, and those of anti-inflammatory cytokines were increased (35).…”

Post-stroke inflammation and the potential efficacy of novel stem cell therapies: focus on amnion epithelial cells

“…For example, transplanted hAECs produce neurotrophic substances and stimulate repair and regeneration of host neurons in a primate model of spinal cord injury (Sankar and Muthusamy, 2003). In addition, hAECs transplanted into the cerebral lateral ventricle of a transgenic mouse model of Alzheimer's disease were found to rescue damaged cholinergic neurons (Xue et al, 2012). The authors reported that hAEC treatment increased the number of cholinergic neurons, as well as the level of acetylcholine produced by these cells, which was suggested to be largely responsible for the reversal of cognitive decline in this animal model.…”

Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats

“…In our recent studies, transplantation of human NSCs overexpressing choline acetyltransferase (ChAT) gene improved the learning and memory functions of AD model and aging animals by increasing acetylcholine (ACh) concentration [17–19]. Notably, brain and reproductive organs including placenta contain high levels of ChAT, and amniotic membrane epithelial stem cells (AMESCs) and amniotic membrane‐derived mesenchymal stem cells (AMMSCs) express ChAT and secrete ACh [20–22]. Indeed, transplantation of AMESCs and AMMSCs ameliorated spatial memory deficit in AD model animals [22, 23].…”