Wharton’s Jelly-derived mesenchymal stem cells alleviate memory deficits and reduce amyloid-β deposition in an APP/PS1 transgenic mouse model

Abstract

Alzheimer's disease (AD) is the leading cause of dementia in the elderly and is characterized by amyloid plaques, neurofibrillary tangles, and neuronal loss. Cumulative evidence supports that neuroinflammation is an important factor for the pathogenesis of AD and contributes to amyloid beta (Aβ) generation. However, there has been no effective treatment for AD. Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have a potential therapeutic effect in the treatment for neurological diseases. In the present study, we evaluated the therapeutic effect of WJ-MSC transplantation on the neuropathology and memory deficits in amyloid precursor protein (APP) and presenilin-1 (PS1) double-transgenic mice and discussed the mechanism. WJ-MSCs were intravenously transplanted into the APP/PS1 mice. Four weeks after treatment, WJ-MSCs significantly improved the spatial learning and alleviated the memory decline in the APP/PS1 mice. Aβ deposition and soluble Aβ levels were significantly reduced after WJ-MSC treatment. Furthermore, WJ-MSCs significantly increased the expression of the anti-inflammatory cytokine, IL-10. Meanwhile, pro-inflammatory microglial activation and the expressions of pro-inflammatory cytokines, IL-1β and TNFα, were significantly down-regulated by WJ-MSC treatment. Thus, our findings suggest that WJ-MSCs might produce beneficial effects on the prevention and treatment for AD through modulation of neuroinflammation.

Comparison between the effect of human Wharton’s jelly–derived mesenchymal stem cells and levetiracetam on brain infarcts in rats

“…In addition, the expression of one of the antioxidant proteins was increased by the administration of LEV. 37 F I G U R E 4 A, Section of rat hippocampus of combined LEV-and SC-treated group showed high GFAP expression (IHC × 100). 33 An interesting finding of our study is that we found an upregulation of iNOS gene expression in the LEV-treated group.…”

Microglia‐targeted stem cell therapies for Alzheimer disease: A preclinical data review

“…MSCs applied in AD rodent studies have been isolated from bone marrow (BM‐MSCs) (Naaldijk et al, ), adipose tissue (ADSCs) (Ma et al, ), umbilical cord Wharton's jelly (WJ‐MSCs) (Xie et al, ), umbilical cord blood (UCB‐MSCs) (Lee H. J., et al, ), and amniotic membrane (AMSCs) (Kim K. S., et al, ). They have captured considerable scientific interest for their tissue repair and immunomodulation (Li, Guo, & Ikehara, ; Tolar, Le Blanc, Keating, & Blazar, ) and possess the capacity to transdifferentiate into a variety of cell types (Phinney & Prockop, ).…”

“…WJ‐MSCs have shown multiple differentiation potentials and the ability to provide trophic support (Carvalho, Teixeira, Reis, Sousa, & Salgado, ). Furthermore, intravenous transplantation of stem cells significantly reduced Aβ, increased the expression of anti‐inflammatory cytokines, and downregulated proinflammatory cytokines, suggesting a potential therapeutic agent for AD (Xie et al, ). In contrast, UCB‐MSCs were uniquely shown to have a higher rate of cell proliferation but a limited life span (Zhao, Qu, Liu, Du, & Mu, ).…”

“…However, microglia have also been shown to become more ramified with more processes per cell after stem cell therapy in AD rats (Naaldijk et al, ), which is associated with the ability of microglia to screen their microenvironment and protect hippocampal neurons (Vinet et al, ). Conversely, some studies indicate that transplanted stem cells strongly induce microglial activation, as characterized by an increased number of microglia (Kim J. Y., et al, ; Kim K. S., et al, ; Lee J. K., et al, ; Lee J. K., et al, ; Lee H. J., et al, ; Ma et al, ; Xie et al, ). However, other studies have shown significantly decreased numbers of active microglia following MSC transplantations (Lee I. S., et al, ; Naaldijk et al, ; Zhang et al, ).…”

“…In Table , all studies testing proinflammatory cytokines show that stem cell transplantation dramatically downregulates expression levels of these cytokines and provides neuroprotective effects in AD mice. Furthermore, anti‐inflammatory factors released by microglia after cell therapy inhibit the production of proinflammatory cytokines (Xie et al, ). Together, these results suggest that stem cell transplantation regulates microglia from a proinflammatory status to an anti‐inflammatory status.…”