Induced Pluripotent Stem Cells Meet Genome Editing

Hockemeyer, Dirk; Jaenisch, Rudolf

doi:10.1016/j.stem.2016.04.013

Cited by 412 publications

(339 citation statements)

References 197 publications

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“…When different JAG1 mutations were engineered onto the same genetic background, the mutations (Cys829X and ALGS2) found in subjects with severe liver disease impaired organoid development, while a mutation (Gly274Asp) causing TOF in subjects without liver disease did not impair organoid formation. The combined use of iPSCs and genome editing technologies has enabled revolutionary advances in many areas (61). Our results indicate how this organoid system and genome editing can be jointly used to determine how human disease-causing mutations affect organ development and the pathogenesis of human genetic diseases.…”

Section: Discussionmentioning

confidence: 81%

Human hepatic organoids for the analysis of human genetic diseases

Guan¹,

Xu²,

Garfin³

et al. 2017

JCI Insight

176

196

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Section: Discussionmentioning

confidence: 81%

Human hepatic organoids for the analysis of human genetic diseases

Guan¹,

Xu²,

Garfin³

et al. 2017

JCI Insight

176

196

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“…Other cells from easier to harvest sources have been differentiated into Schwann‐like cells, including skin‐derived precursors, mesenchymal stem cells, and adipose tissue‐derived stem cells,41, 44, 45 although these too would have limited utility in inherited myelin disorders, and difficulty with scale of production. iPSCs are a highly attractive source for cell therapy because they are easy to generate, are infinitely expandable, and can be readily manipulated using genome‐editing techniques to correct disease gene defects 46. Several groups have reported differentiating Schwann‐like cells from iPSCs 29, 47, 48.…”

Section: Discussionmentioning

confidence: 99%

Cell transplantation strategies for acquired and inherited disorders of peripheral myelin

Muhammad

Kim

Epifantseva

et al. 2018

Ann Clin Transl Neurol

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ObjectiveTo investigate transplantation of rat Schwann cells or human iPSC‐derived neural crest cells and derivatives into models of acquired and inherited peripheral myelin damage.MethodsPrimary cultured rat Schwann cells labeled with a fluorescent protein for monitoring at various times after transplantation. Human‐induced pluripotent stem cells (iPSCs) were differentiated into neural crest stem cells, and subsequently toward a Schwann cell lineage via two different protocols. Cell types were characterized using flow cytometry, immunocytochemistry, and transcriptomics. Rat Schwann cells and human iPSC derivatives were transplanted into (1) nude rats pretreated with lysolecithin to induce demyelination or (2) a transgenic rat model of dysmyelination due to PMP22 overexpression.ResultsRat Schwann cells transplanted into sciatic nerves with either toxic demyelination or genetic dysmyelination engrafted successfully, and migrated longitudinally for relatively long distances, with more limited axial migration. Transplanted Schwann cells engaged existing axons and displaced dysfunctional Schwann cells to form normal‐appearing myelin. Human iPSC‐derived neural crest stem cells and their derivatives shared similar engraftment and migration characteristics to rat Schwann cells after transplantation, but did not further differentiate into Schwann cells or form myelin.InterpretationThese results indicate that cultured Schwann cells surgically delivered to peripheral nerve can engraft and form myelin in either acquired or inherited myelin injury, as proof of concept for pursuing cell therapy for diseases of peripheral nerve. However, lack of reliable technology for generating human iPSC‐derived Schwann cells for transplantation therapy remains a barrier in the field.

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“…Moreover, detection of slight phenotypic changes between cells differentiated from a patient or control iPSCs may not reveal a relevant phenotypic difference between both groups of cells but rather reflect the system's intrinsic dissimilarity between individual iPSC lines [27]. It is for that reason that isogenic pairs composed of diseasespecific and control iPSCs that differ exclusively at the diseasecausing mutation have been generated, being presently the best disease in a dish model strategy [28,29]. This approach has been possible thanks to last advances in gene editing (CRISPR-Cas9; TALENs; ZFN) [30,31].…”

Section: Discussionmentioning

confidence: 99%

Out with the Old, in with the New… Strategies Based on Stem Cells to Design New Models of Alzheimer’s Disease

Revilla¹

2017

JSRT

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Since Yamanaka's group successfully discovered iPSCs technology a decade ago, new approaches for disease modeling have happened in the field. iPSCs have become the primary alternative to ESCs and is considered as a potential tool for modeling neurodegenerative diseases. The most prevalent form of dementia worldwide is AD, with aging being the major risk factor to develop it. Although it was described more than a hundred years ago, currently it doesn't exist a cure for this disorder, and ordinary treatments can only temporarily alleviate their symptoms. It has been reported that only 5% of AD cases are inherited, showing the remaining 95% a sporadic origin. Our understanding of AD pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the limitations to model the sporadic form of the disease. Given that, iPSCs can be derived from somatic cells of AD patients and subsequently be differentiated into neurons, the development of therapies based on the use of stem cells might be a promising novel tool for cellular replacement therapy, in addition to disease modeling and drug discovery for AD. Direct reprogramming, cocktails of small molecules, gene editing or 3D cell culture are among those new strategies that are improving the application of stem cells in regenerative medicine. Here, we show how present approaches in the field of iPSCs can contribute to create novel AD disease models.

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Induced Pluripotent Stem Cells Meet Genome Editing

Cited by 412 publications

References 197 publications

Human hepatic organoids for the analysis of human genetic diseases

Human hepatic organoids for the analysis of human genetic diseases

Cell transplantation strategies for acquired and inherited disorders of peripheral myelin

Out with the Old, in with the New… Strategies Based on Stem Cells to Design New Models of Alzheimer’s Disease

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