Controlled Cortical Impact Model of Mouse Brain Injury with Therapeutic Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Cells

10.3791/59561 ◽  
2019 ◽  
Author(s):  
Orion Furmanski ◽  
Michael D. Nieves ◽  
Martin L. Doughty
Keyword(s):  
Stem Cell ◽  
Brain Injury ◽  
Mouse Brain ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Neural Cells ◽  
Impact Model ◽  
Controlled Cortical Impact ◽  
Therapeutic Transplantation ◽  
Induced Pluripotent

Lithium chloride improves the efficiency of induced pluripotent stem cell-derived neurospheres

2015 ◽  
Vol 396 (8) ◽  
pp. 923-928 ◽  
Author(s):  
Azita Parvaneh Tafreshi ◽  
Aude Sylvain ◽  
Guizhi Sun ◽  
Daniella Herszfeld ◽  
Keith Schulze ◽  
...  
Keyword(s):  
Stem Cell ◽  
Lithium Chloride ◽  
Pluripotent Stem Cell ◽  
Lithium Treatment ◽  
Formation Rate ◽  
Induced Pluripotent Stem Cell ◽  
Neural Progenitors ◽  
Neural Cells ◽  
Proliferating Cells ◽  
Induced Pluripotent

Abstract Induced pluripotent stem cell (iPSC)-derived neurospheres, which consist mainly of neural progenitors, are considered to be a good source of neural cells for transplantation in regenerative medicine. In this study, we have used lithium chloride, which is known to be a neuroprotective agent, in an iPSC-derived neurosphere model, and examined both the formation rate and size of the neurospheres as well as the proliferative and apoptotic status of their contents. Our results showed that lithium enhanced the formation and the sizes of the iPSC-derived neurospheres, increased the number of Ki67-positive proliferating cells, but reduced the number of the TUNEL-positive apoptotic cells. This increased number of Ki67 proliferating cells was secondary to the decreased apoptosis and not to the stimulation of cell cycle entry, as the expression of the proliferation marker cyclin D1 mRNA did not change after lithium treatment. Altogether, we suggest that lithium enhances the survival of neural progenitors and thus the quality of the iPSC-derived neurospheres, which may strengthen the prospect of using lithium-treated pluripotent cells and their derivatives in a clinical setting.

scholarly journals Human Induced Pluripotent Stem Cell-Derived Models to Investigate Human Cytomegalovirus Infection in Neural Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49700 ◽  
Author(s):  
Leonardo D'Aiuto ◽  
Roberto Di Maio ◽  
Brianna Heath ◽  
Giorgio Raimondi ◽  
Jadranka Milosevic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Cytomegalovirus ◽  
Cytomegalovirus Infection ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Neural Cells ◽  
Human Cytomegalovirus Infection ◽  
Induced Pluripotent

scholarly journals MeCP2 Regulates the Synaptic Expression of a Dysbindin-BLOC-1 Network Component in Mouse Brain and Human Induced Pluripotent Stem Cell-Derived Neurons

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65069 ◽  
Author(s):  
Jennifer Larimore ◽  
Pearl V. Ryder ◽  
Kun-Yong Kim ◽  
L. Alex Ambrose ◽  
Christopher Chapleau ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mouse Brain ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Induced Pluripotent ◽  
Network Component

scholarly journals Exosome/microvesicle content is altered in leucine‐rich repeat kinase 2 mutant induced pluripotent stem cell‐derived neural cells

2019 ◽  
Vol 528 (7) ◽  
pp. 1203-1215
Author(s):  
Kate M. Candelario ◽  
Leonora Balaj ◽  
Tong Zheng ◽  
Johan Skog ◽  
Bjorn Scheffler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Neural Cells ◽  
Leucine Rich Repeat ◽  
Induced Pluripotent

scholarly journals Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain

Cell Reports ◽  
2013 ◽  
Vol 3 (3) ◽  
pp. 646-650 ◽  
Author(s):  
Marina E. Emborg ◽  
Yan Liu ◽  
Jiajie Xi ◽  
Xiaoqing Zhang ◽  
Yingnan Yin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Nonhuman Primate ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Neural Cells ◽  
Primate Brain ◽  
Induced Pluripotent

scholarly journals Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses

2020 ◽  
Vol 19 (6) ◽  
pp. 1017-1034 ◽  
Author(s):  
Sonia Podvin ◽  
Alexander Jones ◽  
Qing Liu ◽  
Brent Aulston ◽  
Linnea Ransom ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mouse Brain ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Chromosome 17 ◽  
Tau Pathology ◽  
Specific Proteins ◽  
Induced Pluripotent ◽  
And Control

Accumulation and propagation of hyperphosphorylated Tau (p-Tau) is a common neuropathological hallmark associated with neurodegeneration of Alzheimer's disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and related tauopathies. Extracellular vesicles, specifically exosomes, have recently been demonstrated to participate in mediating Tau propagation in brain. Exosomes produced by human induced pluripotent stem cell (iPSC)-derived neurons expressing mutant Tau (mTau), containing the P301L and V337M Tau mutations of FTDP-17, possess the ability to propagate p-Tau pathology after injection into mouse brain. To gain an understanding of the mTau exosome cargo involved in Tau pathogenesis, these pathogenic exosomes were analyzed by proteomics and bioinformatics. The data showed that mTau expression dysregulates the exosome proteome to result in 1) proteins uniquely present only in mTau, and not control exosomes, 2) the absence of proteins in mTau exosomes, uniquely present in control exosomes, and 3) shared proteins which were significantly upregulated or downregulated in mTau compared with control exosomes. Notably, mTau exosomes (not control exosomes) contain ANP32A (also known as I1PP2A), an endogenous inhibitor of the PP2A phosphatase which regulates the phosphorylation state of p-Tau. Several of the mTau exosome-specific proteins have been shown to participate in AD mechanisms involving lysosomes, inflammation, secretases, and related processes. Furthermore, the mTau exosomes lacked a substantial portion of proteins present in control exosomes involved in pathways of localization, vesicle transport, and protein binding functions. The shared proteins present in both mTau and control exosomes represented exosome functions of vesicle-mediated transport, exocytosis, and secretion processes. These data illustrate mTau as a dynamic regulator of the biogenesis of exosomes to result in acquisition, deletion, and up- or downregulation of protein cargo to result in pathogenic mTau exosomes capable of in vivo propagation of p-Tau neuropathology in mouse brain.

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