scholarly journals The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative Medicine

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Erin C. Hedges ◽  
Vera J. Mehler ◽  
Agnes L. Nishimura
Keyword(s):  
Stem Cells ◽  
Amyotrophic Lateral Sclerosis ◽  
Regenerative Medicine ◽  
Frontotemporal Dementia ◽  
Cell Lines ◽  
Pluripotent Stem Cells ◽  
Basic Research ◽  
Patient Specific ◽  
Exogenous Dna ◽  
Lateral Sclerosis

In recent years several genes have linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) as a spectrum disease; however little is known about what triggers their onset. With the ability to generate patient specific stem cell lines from somatic cells, it is possible to model disease without the need to transfect cells with exogenous DNA. These pluripotent stem cells have opened new avenues for identification of disease phenotypes and their relation to specific molecular pathways. Thus, as never before, compounds with potential applications for regenerative medicine can be specifically tailored in patient derived cultures. In this review, we discuss how patient specific induced pluripotent stem cells (iPSCs) have been used to model ALS and FTD and the most recent drug screening targets for these diseases. We also discuss how an iPSC bank would improve the quality of the available cell lines and how it would increase knowledge about the ALS/FTD disease spectrum.

scholarly journals Patient-Specific Induced Pluripotent Stem Cells for SOD1-Associated Amyotrophic Lateral Sclerosis Pathogenesis Studies

Acta Naturae ◽  
2014 ◽  
Vol 6 (1) ◽  
pp. 54-60 ◽  
Author(s):  
I. V. Chestkov ◽  
E. A. Vasilieva ◽  
S. N. Illarioshkin ◽  
M. A. Lagarkova ◽  
S. L. Kiselev
Keyword(s):  
Stem Cells ◽  
Amyotrophic Lateral Sclerosis ◽  
Induced Pluripotent Stem Cells ◽  
Motor Neurons ◽  
Pluripotent Stem Cells ◽  
Ips Cells ◽  
The Body ◽  
Patient Specific ◽  
Induced Pluripotent ◽  
Lateral Sclerosis

The genetic reprogramming technology allows one to generate pluripotent stem cells for individual patients. These cells, called induced pluripotent stem cells (iPSCs), can be an unlimited source of specialized cell types for the body. Thus, autologous somatic cell replacement therapy becomes possible, as well as the generation of in vitro cell models for studying the mechanisms of disease pathogenesis and drug discovery. Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder that leads to a loss of upper and lower motor neurons. About 10% of cases are genetically inherited, and the most common familial form of ALS is associated with mutations in the SOD1 gene. We used the reprogramming technology to generate induced pluripotent stem cells with patients with familial ALS. Patient-specific iPS cells were obtained by both integration and transgene-free delivery methods of reprogramming transcription factors. These iPS cells have the properties of pluripotent cells and are capable of direct differentiation into motor neurons.

scholarly journals Nonhuman Primate Induced Pluripotent Stem Cells in Regenerative Medicine

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Yuehong Wu ◽  
Anuja Mishra ◽  
Zhifang Qiu ◽  
Steven Farnsworth ◽  
Suzette D. Tardif ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Cell Lines ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Ips Cell ◽  
Disease States ◽  
Autologous Cell Therapy ◽  
Induced Pluripotent

Among the various species from which induced pluripotent stem cells have been derived, nonhuman primates (NHPs) have a unique role as preclinical models. Their relatedness to humans and similar physiology, including central nervous system, make them ideal for translational studies. We review here the progress made in deriving and characterizing iPS cell lines from different NHP species. We focus on iPS cell lines from the marmoset, a small NHP in which several human disease states can be modeled. The marmoset can serve as a model for the implementation of patient-specific autologous cell therapy in regenerative medicine.

scholarly journals Advances in Patient-Specific Induced Pluripotent Stem Cells Shed Light on Drug Discovery for Amyotrophic Lateral Sclerosis

2018 ◽  
Vol 27 (9) ◽  
pp. 1301-1312 ◽  
Author(s):  
Jui-Hao Lee ◽  
Jen-Wei Liu ◽  
Shinn-Zong Lin ◽  
Horng-Jyh Harn ◽  
Tzyy-Wen Chiou
Keyword(s):  
Stem Cells ◽  
Amyotrophic Lateral Sclerosis ◽  
Induced Pluripotent Stem Cells ◽  
Motor Neurons ◽  
Pluripotent Stem Cells ◽  
Neurological Diseases ◽  
New Drugs ◽  
Patient Specific ◽  
Induced Pluripotent ◽  
Lateral Sclerosis

Induced pluripotent stem cells (iPSCs), which are generated through reprogramming adult somatic cells by expressing specific transcription factors, can differentiate into derivatives of the three embryonic germ layers and accelerate rapid advances in stem cell research. Neurological diseases such as amyotrophic lateral sclerosis (ALS) have benefited enormously from iPSC technology. This approach can be particularly important for creating iPSCs from patients with familial or sporadic forms of ALS. Motor neurons differentiated from the ALS-patient-derived iPSC can help to determine the relationship between cellular phenotype and genotype. Patient-derived iPSCs facilitate the development of new drugs and/or drug screening for ALS treatment and allow the exploration of the possible mechanism of ALS disease. In this article, we reviewed ALS-patient-specific iPSCs with various genetic mutations, progress in drug development for ALS disease, functional assays showing the differentiation of iPSCs into mature motor neurons, and promising biomarkers in ALS patients for the evaluation of drug candidates.

scholarly journals A Comprehensive Library of Familial Human Amyotrophic Lateral Sclerosis Induced Pluripotent Stem Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0118266 ◽  
Author(s):  
Ying Li ◽  
Umamahesw Balasubramanian ◽  
Devon Cohen ◽  
Ping-Wu Zhang ◽  
Elizabeth Mosmiller ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amyotrophic Lateral Sclerosis ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent ◽  
Lateral Sclerosis

scholarly journals Modeling Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism dementia Complex with Microglia Containing Cerebral Organoids Derived from Induced Pluripotent Stem Cells

2021 ◽  
Author(s):  
Yiling Hong ◽  
Xu Dong ◽  
Lawrence Chang ◽  
Mariann Chang ◽  
Chen Xie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Disease ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
M2 Microglia ◽  
Matrix Organization ◽  
Induced Pluripotent ◽  
Lateral Sclerosis

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.

scholarly journals Genome maintenance in pluripotent stem cells

2014 ◽  
Vol 204 (2) ◽  
pp. 153-163 ◽  
Author(s):  
Uri Weissbein ◽  
Nissim Benvenisty ◽  
Uri Ben-David
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
In Vitro Propagation ◽  
Basic Research ◽  
Culture Conditions ◽  
Genome Maintenance ◽  
Self Renewal ◽  
Genomic Aberrations

Pluripotent stem cells (PSCs) must maintain their proper genomic content in order to preserve appropriate self-renewal and differentiation capacities. However, their prolonged in vitro propagation, as well as the environmental culture conditions, present serious challenges to genome maintenance. Recent work has been focused on potential means to alleviate the genomic insults experienced by PSCs, and to detect them as soon as they arise, in order to prevent the detrimental consequences of these genomic aberrations on PSC application in basic research and regenerative medicine.

scholarly journals Genome Editing Redefines Precision Medicine in the Cardiovascular Field

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Elda Dzilic ◽  
Harald Lahm ◽  
Martina Dreßen ◽  
Marcus-André Deutsch ◽  
Rüdiger Lange ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Precision Medicine ◽  
Genome Editing ◽  
Pluripotent Stem Cells ◽  
New Technologies ◽  
Basic Research ◽  
Disease Modelling ◽  
Ethical Implications ◽  
Regenerative Therapies

Genome editing is a powerful tool to study the function of specific genes and proteins important for development or disease. Recent technologies, especially CRISPR/Cas9 which is characterized by convenient handling and high precision, revolutionized the field of genome editing. Such tools have enormous potential for basic science as well as for regenerative medicine. Nevertheless, there are still several hurdles that have to be overcome, but patient-tailored therapies, termed precision medicine, seem to be within reach. In this review, we focus on the achievements and limitations of genome editing in the cardiovascular field. We explore different areas of cardiac research and highlight the most important developments: (1) the potential of genome editing in human pluripotent stem cells in basic research for disease modelling, drug screening, or reprogramming approaches and (2) the potential and remaining challenges of genome editing for regenerative therapies. Finally, we discuss social and ethical implications of these new technologies.

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