scholarly journals Tumourigenicity and Immunogenicity of Induced Neural Stem Cell Grafts Versus Induced Pluripotent Stem Cell Grafts in Syngeneic Mouse Brain

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Mou Gao ◽  
Hui Yao ◽  
Qin Dong ◽  
Hongtian Zhang ◽  
Zhijun Yang ◽  
...  
2020 ◽  
Vol 11 (1) ◽  
pp. 15 ◽  
Author(s):  
T. Hiran Perera ◽  
Xi Lu ◽  
Laura A Smith Callahan

Low neural tissue extracellular matrix (ECM) content has led to the understudy of its effects on neural cells and tissue. Hyaluronic acid (HA) and laminin are major neural ECM components, but direct comparisons of their cellular effects could not be located in the literature. The current study uses human-induced pluripotent stem-cell-derived neural stem cells to assess the effects of HA, laminin, and HA with laminin-derived peptides IKVAV and LRE on cellular morphology, attachment, neurite extension and ECM remodeling. Increased attachment was observed on HA with and without IKVAV and LRE compared to laminin. Cellular morphology and neurite extension were similar on all surfaces. Using a direct binding inhibitor of Cav2.2 voltage gated calcium channel activity, a known binding partner of LRE, reduced attachment on HA with and without IKVAV and LRE and altered cellular morphology on surfaces with laminin or IKVAV and LRE. HA with IKVAV and LRE reduced the fluorescent intensity of fibronectin staining, but did not alter the localization of ECM remodeling enzymes matrix metalloprotease 2 and 9 staining compared to HA. Overall, the data indicate HA, IKVAV and LRE have complementary effects on human-induced pluripotent stem-cell-derived neural stem cell behavior.


PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65069 ◽  
Author(s):  
Jennifer Larimore ◽  
Pearl V. Ryder ◽  
Kun-Yong Kim ◽  
L. Alex Ambrose ◽  
Christopher Chapleau ◽  
...  

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Emily W. Baker ◽  
Simon R. Platt ◽  
Vivian W. Lau ◽  
Harrison E. Grace ◽  
Shannon P. Holmes ◽  
...  

2020 ◽  
Vol 19 (6) ◽  
pp. 1017-1034 ◽  
Author(s):  
Sonia Podvin ◽  
Alexander Jones ◽  
Qing Liu ◽  
Brent Aulston ◽  
Linnea Ransom ◽  
...  

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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