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

Честков, И. В.; Vasilieva, E. A.; Иллариошкин, С.Н.; Lagarkova, M. A.; Киселев, С. Л.

doi:10.32607/20758251-2014-6-1-54-60

Cited by 39 publications

(22 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These non-neuronal cells associated with peripheral motor nerves may provide additional information related to the pathogenic mechanisms of sporadic ALS once hiPSC-derived motor neurons could be produced from them. Of note, the growth and differentiation of peripheral motor nerve fibroblast-derived hiPSCs shown in this work seemed to be comparable to those hiPSCs derived from adult skin fibroblasts described elsewhere (Chestkov et al, 2014 ).…”

Section: Discussionsupporting

confidence: 85%

Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration

Alves

Dariolli

Jorge

et al. 2015

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that leads to widespread motor neuron death, general palsy and respiratory failure. The most prevalent sporadic ALS form is not genetically inherited. Attempts to translate therapeutic strategies have failed because the described mechanisms of disease are based on animal models carrying specific gene mutations and thus do not address sporadic ALS. In order to achieve a better approach to study the human disease, human induced pluripotent stem cell (hiPSC)-differentiated motor neurons were obtained from motor nerve fibroblasts of sporadic ALS and non-ALS subjects using the STEMCCA Cre-Excisable Constitutive Polycistronic Lentivirus system and submitted to microarray analyses using a whole human genome platform. DAVID analyses of differentially expressed genes identified molecular function and biological process-related genes through Gene Ontology. REVIGO highlighted the related functions mRNA and DNA binding, GTP binding, transcription (co)-repressor activity, lipoprotein receptor binding, synapse organization, intracellular transport, mitotic cell cycle and cell death. KEGG showed pathways associated with Parkinson's disease and oxidative phosphorylation, highlighting iron homeostasis, neurotrophic functions, endosomal trafficking and ERK signaling. The analysis of most dysregulated genes and those representative of the majority of categorized genes indicates a strong association between mitochondrial function and cellular processes possibly related to motor neuron degeneration. In conclusion, iPSC-derived motor neurons from motor nerve fibroblasts of sporadic ALS patients may recapitulate key mechanisms of neurodegeneration and may offer an opportunity for translational investigation of sporadic ALS. Large gene profiling of differentiated motor neurons from sporadic ALS patients highlights mitochondrial participation in the establishment of autonomous mechanisms associated with sporadic ALS.

show abstract

Section: Discussionsupporting

confidence: 85%

Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration

Alves

Dariolli

Jorge

et al. 2015

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…This appeared to be related to neurofilament misregulation and also resulted in axonal pathology in the affected cells (Chen et al, 2014). Other iPSC-lines from patients carrying SOD1 mutations have been created including the SOD1 L144F mutation (detailed as part of the discussion on iPSC-derived motor neuron differentiation)(Dimos et al, 2008) and more recently SOD1 N87S and SOD1 S106L (Chestkov et al, 2014)…”

Section: Human Ipsc-derived Neural Cells For In Vitro Als Modeling (Fmentioning

confidence: 99%

Induced pluripotent stem cells from ALS patients for disease modeling

Richard

Maragakis

2015

Brain Research

View full text Add to dashboard Cite

The ability to reprogram adult somatic cells into pluripotent stem cells that can differentiate into all three germ layers of the developing human has fundamentally changed the landscape of biomedical research. For a neurodegenerative disease like Amyotrophic Lateral Sclerosis (ALS), which does not manifest itself until adulthood and is a heterogeneous disease with few animal models, this technology may be particularly important. Induced pluripotent stem cells (iPSC) have been created from patients with several familial forms of ALS as well as some sporadic forms of ALS. These cells have been differentiated into ALS-relevant cell subtypes including motor neurons and astrocytes, among others. ALS-relevant pathologies have also been identified in motor neurons from these cells and may provide a window into understanding disease mechanisms in vitro. Given that this is a relatively new field of research, numerous challenges remain before iPSC methodologies can fulfill their potential as tools for modeling ALS as well as providing a platform for the investigation of ALS therapeutics.

show abstract

“…Previous studies have shown that removing some obstacles [ 69 - 73 ] and activating innate immunity [ 74 ] could promote reprogramming efficiency, and using piggyBac (PB) transposition could eliminate the potential dangers of insertion [ 75 - 79 ]. Moreover, besides obtaining iPS cells from blood [ 80 ] and primary skin fibroblasts [ 81 ], generating a non-viral human iPS cell bank from donors has been achieved [ 82 ], based on previous virus-based methods [ 83 - 86 ]. Considering the rapid progress of this area, involving safer, more affordable, more efficient, and more convenient protocols, it is conceivable that this methodology will in the near future be used clinically, for various human tissues.…”

Section: Applications and Expectationsmentioning

confidence: 99%

Non-Viral Methods For Generating Integration-Free, Induced Pluripotent Stem Cells

Deng¹,

Wang²,

Wang³

et al. 2015

CSCR

View full text Add to dashboard Cite

Induced pluripotent stem (iPS) cells were created from mouse fibroblasts by induced expression of Yamanaka factors, Oct3/4, Sox2, Klf4, and c-Myc. This technique has quickly resulted in an exponential increase in the amount of pluripotency studies, and has provided a valuable tool in regenerative medicine. At the same time, many methodologies to generate iPS cells have been reported, and are comprised mainly of viral methods and non-viral methods. Although viral methods may not be applicable for clinical applications, various nonviral methods have been reported in recent years, including DNA vector-based approaches, transfection of mRNA, transduction of reprogramming proteins, and use of small molecule compounds. This review summarizes and evaluates these non-viral methods.

show abstract

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

Cited by 39 publications

References 25 publications

Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration

Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration

Induced pluripotent stem cells from ALS patients for disease modeling

Non-Viral Methods For Generating Integration-Free, Induced Pluripotent Stem Cells

Contact Info

Product

Resources

About