Amniotic Mesenchymal Stem Cells Decrease Aβ Deposition and Improve Memory in APP/PS1 Transgenic Mice

Abstract

Transplantation of human amniotic mesenchymal stem cells (hAM-MSCs) seems to be a promising strategy for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, the clinical therapeutic effects of hAM-MSCs and their mechanisms of action in AD remain to be determined. Here, we used amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice to evaluate the effects of hAM-MSC transplantation on AD-related neuropathology and cognitive dysfunction. We found that hAM-MSC transplantation into the hippocampus dramatically reduced amyloid-β peptide (Aβ) deposition and rescued spatial learning and memory deficits in APP/PS1 mice. Interestingly, these effects were associated with increasing in Aβ-degrading factors, elevations in activated microglia, and the modulation of neuroinflammation. Furthermore, enhanced hippocampal neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG) and enhanced synaptic plasticity following hAM-MSC treatment could be another important factor in reversing the cognitive decline in APP/PS1 mice. Instead, the mechanism underlying the improved cognition apparently involves a robust increase in hippocampal synaptic density and neurogenesis that is mediated by brain-derived neurotrophic factor (BDNF). In conclusion, our data suggest that hAM-MSCs may be a new and effective therapy for the treatment of AD.

Characteristics and Therapeutic Potential of Human Amnion-Derived Stem Cells

“…Alzheimer's Disease (AD) is the most common chronic neurodegenerative disease as showing extensive degeneration in a variety types of neurons [96]. Studies showed that hAMSCs transplantation might alleviate the pathological alternation and facilitate the restoration of the memory functions in AD mice by attenuating oxidative stress [97] or breaking Aβ deposition [98]. Similar with the study, transplantation of hAESCs into the lateral ventricles of APP/PS1 AD mice increased the numbers of cholinergic neurons and acetylcholine concentration in hippocampus [99].…”

Mesenchymal stem cells: As a multi-target cell therapy for clearing β-amyloid deposition in Alzheimer’s disease

“…In addition, MSCs can also eliminate Aβ by enhancing the secretion of Aβ proteolytic enzymes in microglia or upregulating the expression of uptake Aβ receptors in activated microglia (Lee et al, 2010b;Kim et al, 2013;Yokokawa et al, 2019;Kim et al, 2018b;Zheng et al, 2017;Zhao et al, 2018;Lee et al, 2009). On the one hand, M2 microglia enhanced the secretion of Aβ proteolytic enzymes NEP, IDE, and matrix metallopeptidase 9 (MMP9).…”

Mesenchymal Stem Cell Therapy for Alzheimer’s Disease

“…Similarly, human amniotic mesenchymal stem cell (AM-MSC) intrahippocampal transplantation significantly diminished Aβ deposition and improved the spatial learning and memory deficits in APP/PS1 mice. Zheng et al suggest that improved cognition may be associated with an increment in hippocampal synaptic density and neurogenesis that is regulated by BDNF [50].…”