Systemic Transplantation of Human Umbilical Cord Derived Mesenchymal Stem Cells-Educated T Regulatory Cells Improved the Impaired Cognition in AβPPswe/PS1dE9 Transgenic Mice

Abstract

Alzheimer’s disease (AD) is one of most prevalent dementias, which is characterized by the deposition of extracellular amyloid-beta protein (Aβ) and the formation of neurofibrillary tangles within neurons. Although stereotaxic transplantation of mesenchymal stem cells (MSCs) into the hippocampus of AD animal model as immunomodulatory cells has been suggested as a potential therapeutic approach to prevent the progress of AD, it is invasive and difficult for clinical perform. Systemic and central nervous system inflammation play an important role in pathogenesis of AD. T regulatory cells (Tregs) play a crucial role in maintaining systemic immune homeostasis, indicating that transplantation of Tregs could prevent the progress of the inflammation. In this study, we aimed to evaluate whether systemic transplantation of purified autologous Tregs from spleens of AβPPswe/PS1dE9 double-transgenic mice after MSCs from human umbilical cords (UC-MSCs) education in vitro for 3 days could improve the neuropathology and cognition deficits in AβPPswe/PS1dE9 double-transgenic mice. We observed that systemic transplantation of autologous Tregs significantly ameliorate the impaired cognition and reduced the Aβ plaque deposition and the levels of soluble Aβ, accompanied with significantly decreased levels of activated microglia and systemic inflammatory factors. In conclusion, systemic transplantation of autologous Tregs may be an effective and safe intervention to prevent the progress of AD.

CD4 + T Cells and Neuroprotection: Relevance to Motoneuron Injury and Disease

“…The results of those studies indicate that the Th2, and not the Th1, cell subset is critical for FMN survival levels to equal WT after axotomy (Deboy et al 2006a). These data are consistent with studies indicating that a shift toward the activation of a Th2 cell may delay neurodegenerative disease onset and/or inhibit disease progression (Reynolds et al 2010; Yang et al 2013). More recently, there has been the discovery of additional T cell subsets, including Tregulatory cells (Tregs), which may dampen the initiation and/or development of pro-inflammatory immune responses, and are considered to be anti-inflammatory.…”

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

“…An increase in the levels of IL-10 was detected 4 weeks after systemic transplantation of purified autologous Tregs from spleens of AbPPswe/PS1dE9 double-transgenic mice after MSCs from human umbilical cords (UC-MSCs) education [42]. In Kim's study, they evaluated the effect of amniotic mesenchymal stem cell (AMSC) administration on inflammatory cytokines, and they observed an increase in IL-10 in the AMSCs-AD group at 1 week after injection, and this effect lasted until 12 weeks after AMSC injection [43].…”

A Perspective on Roles Played by Innate and Adaptive Immunity in the Pathobiology of Neurodegenerative Disorders

“…Systemic immunity affects disease pathogenesis by altering the phenotype of microglia (Heneka et al, 2015; Latta et al, 2015; Lucke-Wold et al, 2015; Mhatre et al, 2015; Yamada, 2015; Zhang and Jiang, 2015). As both Teff and Treg were theorized to play a crucial role in maintaining systemic immune homeostasis, the preservation of these cells’ immune functions is likely to control disease tempo (Saresella et al, 2010; Toly-Ndour et al, 2011; Yang et al, 2013; Schwartz and Baruch, 2014; Baruch et al, 2015; Wang et al, 2015). In support of this idea, transplantation of splenocytes acquired from young mice without CNS disease not only prevented AD, but also improved spatial learning and memory in APPswe/PSENldE9 transgenic animals (Wang et al, 2015).…”

“…The observations made provide further support for the importance of immune control in AD pathobiology. Notably, systemic transplantation of purified autologous splenic Tregs into APPswe/PS1dE9 mice ameliorates impaired cognition and reduces plaques and soluble Aβ (Yang et al, 2013). The numbers of activated microglia and accompanying pro-inflammatory responses are also reduced.…”