pubmed: alzheimer's and stem...
NCBI: db=pubmed; Term=alzheimer's and stem cell therapy
NCBI pubmed
  • Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer's disease.

    Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer's disease.

    Brain Res. 2015 Feb 16;

    Authors: Kanamaru T, Kamimura N, Yokota T, Nishimaki K, Iuchi K, Lee H, Takami S, Akashiba H, Shitaka Y, Ueda M, Katsura KI, Kimura K, Ohta S

    Abstract
    Stem cell transplantation therapy is currently in clinical trials for the treatment of ischemic stroke, and several beneficial aspects have been reported. Similarly, in Alzheimer's disease (AD), stem cell therapy is expected to provide an efficient therapeutic approach. Indeed, the intracerebral transplantation of stem cells reduced amyloid-β (Aβ) deposition and rescued memory deficits in AD model mice. Here, we show that intravenous transplantation of bone marrow-derived mononuclear cells (BMMCs) improves cognitive function in two different AD mouse models, DAL and APP mice, and prevents neurodegeneration. GFP-positive BMMCs were isolated from tibiae and femurs of 4-week-old mice and then transplanted intravenously into DAL and APP mice. Transplantation of BMMCs suppressed neuronal loss and restored memory impairment of DAL mice to almost the same level as in wild-type mice. Transplantation of BMMCs to APP mice reduced Aβ deposition in the brain. APP mice treated with BMMCs performed significantly better on behavioral tests than vehicle-injected mice. Moreover, the effects were observed even with transplantation after the onset of cognitive impairment in DAL mice. Together, our results indicate that intravenous transplantation of BMMCs has preventive effects against the cognitive decline in AD model mice and suggest a potential therapeutic effect of BMMC transplantation therapy.

    PMID: 25698614 [PubMed - as supplied by publisher]

pubmed: alzheimer's and stem...
NCBI: db=pubmed; Term=alzheimer's and stem cell treatment
NCBI pubmed
  • N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons.

    N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons.

    Sci Rep. 2015;5:8744

    Authors: Chang CY, Chen SM, Lu HE, Lai SM, Lai PS, Shen PW, Chen PY, Shen CI, Harn HJ, Lin SZ, Hwang SM, Su HL

    Abstract
    Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by scavenging Aβ aggregates and neurofibrillary tangles.

    PMID: 25735452 [PubMed - in process]