Current status of treating neurodegenerative disease with induced pluripotent stem cells

2016 ◽  
Vol 135 (1) ◽  
pp. 57-72 ◽  
Author(s):  
A. E. Pen ◽  
U. B. Jensen
2021 ◽  
Vol 22 (9) ◽  
pp. 4334
Author(s):  
Katrina Albert ◽  
Jonna Niskanen ◽  
Sara Kälvälä ◽  
Šárka Lehtonen

Induced pluripotent stem cells (iPSCs) are a self-renewable pool of cells derived from an organism’s somatic cells. These can then be programmed to other cell types, including neurons. Use of iPSCs in research has been two-fold as they have been used for human disease modelling as well as for the possibility to generate new therapies. Particularly in complex human diseases, such as neurodegenerative diseases, iPSCs can give advantages over traditional animal models in that they more accurately represent the human genome. Additionally, patient-derived cells can be modified using gene editing technology and further transplanted to the brain. Glial cells have recently become important avenues of research in the field of neurodegenerative diseases, for example, in Alzheimer’s disease and Parkinson’s disease. This review focuses on using glial cells (astrocytes, microglia, and oligodendrocytes) derived from human iPSCs in order to give a better understanding of how these cells contribute to neurodegenerative disease pathology. Using glia iPSCs in in vitro cell culture, cerebral organoids, and intracranial transplantation may give us future insight into both more accurate models and disease-modifying therapies.


2009 ◽  
Vol 65 ◽  
pp. S10
Author(s):  
Haruhisa Inoue ◽  
Shiho Kitaoka ◽  
Motoko Naitoh ◽  
Kazutoshi Takahashi ◽  
Katsuhiro Yoshikawa ◽  
...  

Author(s):  
Thach-Vu Ho ◽  
Grace Asuelime ◽  
Wendong Li ◽  
Yanhong Shi

2021 ◽  
Author(s):  
Yiling Hong ◽  
Xu Dong ◽  
Lawrence Chang ◽  
Mariann Chang ◽  
Chen Xie ◽  
...  

Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism dementia Complex (ALS-PDC) is a neurodegenerative disease linked to the traditional consumption of cycad seeds by the Chamorro people of Guam. Little is known about the etiological role of cycad toxin in ALS-PDC. Patient derived induced pluripotent stem cells were derived from age and sex matched affected and unaffected patient lymphoid cells then differentiated into cerebral organoids. After three months, the ALS-PDC affected organoids were smaller, their neurons had less extensive neurite outgrowth, and the organoids had more reactive astrocytes and M1 microglia, fewer resting and M2 microglia, and more open extracellular space. Most of these phenomena could be recapitulated by exposing unaffected organoids to β-methylamino L-alanine (BMAA), a toxic amino acid produced by cyanobacteria living with cycad plants. Furthermore, ALS-PDC affected organoids exhibited an exacerbated neuroinflammatory response to BMAA exposure via activation of caspase1/NLRP3 inflammasome. A genome-wide transcriptome analysis of the organoids showed that the most down regulated pathways were taurine, alanine, aspartate, and glutamate metabolism; protein digestion; and absorption. The most down-regulated biological processes were type I interferon signaling, regulation of neuron differentiation and extracellular matrix organization. Our results suggested that the etiology of ALS-PDC is due to metabolic disorders that shifted microglia to a more proinflammatory M1 state instead of a non-inflammatory, repairing M2 state, which exacerbated inflammation and reduced extracellular matrix strength. Supplementation of transforming growth factor beta to ALS/PDC affected organoids increased the expression of interferon-induced transmembrane proteins (IFITMs) and restored M2 microglia populations and extracellular matrix organization. Organoids containing networks of neurons, astrocytes, microglia derived from iPSC with our protocol provides an excellent cellular model for neurodegenerative disease modeling.


PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41572 ◽  
Author(s):  
Takuya Yagi ◽  
Arifumi Kosakai ◽  
Daisuke Ito ◽  
Yohei Okada ◽  
Wado Akamatsu ◽  
...  

2013 ◽  
Vol 1 (1) ◽  
pp. 6 ◽  
Author(s):  
Zhiqiang Liu ◽  
Jin Zhou ◽  
Haibin Wang ◽  
Mengge Zhao ◽  
Changyong Wang

2021 ◽  
Vol 2 ◽  
Author(s):  
Henriette Reventlow Frederiksen ◽  
Ulrik Doehn ◽  
Pernille Tveden-Nyborg ◽  
Kristine K. Freude

Neurological disorder is a general term used for diseases affecting the function of the brain and nervous system. Those include a broad range of diseases from developmental disorders (e.g., Autism) over injury related disorders (e.g., stroke and brain tumors) to age related neurodegeneration (e.g., Alzheimer's disease), affecting up to 1 billion people worldwide. For most of those disorders, no curative treatment exists leaving symptomatic treatment as the primary mean of alleviation. Human induced pluripotent stem cells (hiPSC) in combination with animal models have been instrumental to foster our understanding of underlying disease mechanisms in the brain. Of specific interest are patient derived hiPSC which allow for targeted gene editing in the cases of known mutations. Such personalized treatment would include (1) acquisition of primary cells from the patient, (2) reprogramming of those into hiPSC via non-integrative methods, (3) corrective intervention via CRISPR-Cas9 gene editing of mutations, (4) quality control to ensure successful correction and absence of off-target effects, and (5) subsequent transplantation of hiPSC or pre-differentiated precursor cells for cell replacement therapies. This would be the ideal scenario but it is time consuming and expensive. Therefore, it would be of great benefit if transplanted hiPSC could be modulated to become invisible to the recipient's immune system, avoiding graft rejection and allowing for allogenic transplantations. This review will focus on the current status of gene editing to generate non-immunogenic hiPSC and how these cells can be used to treat neurological disorders by using cell replacement therapy. By providing an overview of current limitations and challenges in stem cell replacement therapies and the treatment of neurological disorders, this review outlines how gene editing and non-immunogenic hiPSC can contribute and pave the road for new therapeutic advances. Finally, the combination of using non-immunogenic hiPSC and in vivo animal modeling will highlight the importance of models with translational value for safety efficacy testing; before embarking on human trials.


2009 ◽  
Vol 2009 (8) ◽  
pp. 950-960 ◽  
Author(s):  
Hong-Fen SHEN ◽  
Zhi-Fang YAO ◽  
Gao-Fang XIAO ◽  
Jun-Shuang JIA ◽  
Dong XIAO ◽  
...  

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