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

Kanamaru, Takuya; Kamimura, Naomi; Yokota, Takashi; Nishimaki, Kiyomi; Iuchi, Katsuya; Lee, Hyunjin; Takami, Shinya; Akashiba, Hiroki; Shitaka, Yoshitsugu; Ueda, Masayuki; Katsura, Ken‐ichiro; Kimura, Kazumi; Ohta, Shigeo

doi:10.1016/j.brainres.2015.02.011

Cited by 25 publications

(22 citation statements)

References 37 publications

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“…Mesenchymal stem cellsplay an important role in tissue protection, releasing growth factors, signaling molecules, and cytokines, especially when these tissue receptors are being injured (Uccelli et al, 2011), and according to Abreu-Júnior et al (2014), even secreting neurotrophic factors that favor neurogenesis, angiogenesis, and contribute to synapses and the remyelination of injured axons. These characteristics associated with this cell type are the reason behind their wide use in preclinical and clinical studies as a therapeutic strategy (Moazzami et al, 2014;Kanamaru et al, 2015) and our conducting this investigation to evaluate the clinical effects of MSC therapy on neurological changes developed by dogs affected by canine distemper virus.…”

Section: Discussionmentioning

confidence: 99%

Research Article Mesenchymal stem cell infusion for the treatment of neurological sequelae of canine distemper virus: a clinical study

Gonçalves¹,

Gomes²,

Guterra³

et al. 2018

Genet. Mol. Res.

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We investigated the effects of an allogenic infusion of mesenchymal stem cells derived from adipose tissue for treatment of dogs with neurological sequelae secondary to infection with canine distemper virus. Seven dogs were selected, all of which presented positive PCR for canine distemper and later, after clinical treatment, presented negative PCR but retained at least one post-infection neurological signal. Cell therapy was performed on days 1, 15, and 30; blood samples were taken on days 1 and 30for a hemogram, and the animals were evaluated on days 1, 15, 30, 45, and 180 for walking characteristics, urinary or fecal incontinence, state of consciousness, myoclonus, and occurrence of seizures. A descriptive numerical scale was established for scoring and classifying the various parameters that were evaluated. All the animals demonstrated post-therapy clinical neurological improvement, especially for the parameters walking and urinary and fecal incontinence; this improvement was significant throughout the evaluation period. Allogenic infusion of mesenchymal stem cells derived from adipose ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 17 (4): gmr18088 D.S.V. Gonçalves et al 2 tissue in dogs with neurological sequelae secondary to infection by the canine distemper virus proved to be an efficient treatment.

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Section: Discussionmentioning

confidence: 99%

Research Article Mesenchymal stem cell infusion for the treatment of neurological sequelae of canine distemper virus: a clinical study

Gonçalves¹,

Gomes²,

Guterra³

et al. 2018

Genet. Mol. Res.

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“…Among various types of cell-based therapies for stroke, the application of autologous bone marrow derived mononuclear cells has been one of the most extensively studied for a range of CNS disorders[5, 17–20]. Herein, we sought to determine if there are specific subpopulations of cells within the mononuclear fraction that preferentially account for the seemingly beneficial effects of MNCs in rodent stroke.…”

Section: Discussionmentioning

confidence: 99%

Various Cell Populations Within the Mononuclear Fraction of Bone Marrow Contribute to the Beneficial Effects of Autologous Bone Marrow Cell Therapy in a Rodent Stroke Model

Yang

Parsha

Schaar

et al. 2016

Transl. Stroke Res.

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Cell-based therapies including bone-marrow derived mononuclear cells (MNCs) are now widely being studied because of their pleotropic effects and promising results to improve recovery after stroke in animal models. Unlike other types of cell therapies, MNCs is a mixture of lymphoid, myeloid, erythroid, and stem cell populations. Which cell population(s) accounts for the beneficial effects of MNCs in stroke recovery is unclear. In this paper, we employed a mouse stroke model with middle cerebral artery occlusion (MCAo), and used positively and negatively sorted autologous MNCs by MACs to determine which fractions of the MNCs contribute to their beneficial effects. We evaluated the benefits of neurofunctional recovery produced by individual cell lineages within MNCs in a long-term observation study up to 28 days after stroke. Mortality and modulation of inflammation were also compared among different sub-populations. We further studied the impact of neurotoxicity posed by activated microglia in the presence of different cell lineages within MNCs. We concluded that myeloid cell lineage and stem cell/progenitors appear to be important components within MNCs that contribute to improved outcomes after stroke.

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“…Beyond the above drug explorations, in recent years, stem cell transplantation has been shown to effectively prevent memory impairment and improve cognitive function in AD model mice ( Lee et al, 2010 , 2016 ; Kanamaru et al, 2015 ). The mechanisms involved in stem cell therapies are diverse and mainly include neuronal replacement ( Abdel-Salam, 2011 ), neurotrophic support ( Marsh and Blurton-Jones, 2017 ), and immunomodulation ( Shen et al, 2017 ).…”

Section: Microglia-targeted Therapies In Ad Model Micementioning

confidence: 99%

Clinical PET Imaging of Microglial Activation: Implications for Microglial Therapeutics in Alzheimer’s Disease

Shen

Bao

Wang

2018

Front. Aging Neurosci.

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In addition to extracellular β-amyloid plaques and intracellular neurofibrillary tangles, neuroinflammation has been identified as a key pathological characteristic of Alzheimer’s disease (AD). Once activated, neuroinflammatory cells called microglia acquire different activation phenotypes. At the early stage of AD, activated microglia are mainly dominated by the neuroprotective and anti-inflammatory M2 phenotype. Conversely, in the later stage of AD, the excessive activation of microglia is considered detrimental and pro-inflammatory, turning into the M1 phenotype. Therapeutic strategies targeting the modulation of microglia may regulate their specific phenotype. Fortunately, with the rapid development of in vivo imaging methodologies, visualization of microglial activation has been well-explored. In this review, we summarize the critical role of activated microglia during the pathogenesis of AD and current studies concerning imaging of microglial activation in AD patients. We explore the possibilities for identifying activated microglial phenotypes with imaging techniques and highlight promising therapies that regulate the microglial phenotype in AD mice.

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

Cited by 25 publications

References 37 publications

Research Article Mesenchymal stem cell infusion for the treatment of neurological sequelae of canine distemper virus: a clinical study

Research Article Mesenchymal stem cell infusion for the treatment of neurological sequelae of canine distemper virus: a clinical study

Various Cell Populations Within the Mononuclear Fraction of Bone Marrow Contribute to the Beneficial Effects of Autologous Bone Marrow Cell Therapy in a Rodent Stroke Model

Clinical PET Imaging of Microglial Activation: Implications for Microglial Therapeutics in Alzheimer’s Disease

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