Convergence of human pluripotent stem cell, organoid, and genome editing technologies

Wang, Lin; Ye, Zhaohui; Jang, Yoon Young

doi:10.1177/1535370220985808

Cited by 7 publications

(6 citation statements)

References 179 publications

(177 reference statements)

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“…The development of iPSCs and their differentiation through the formation of organoids that morphologically and physiologically resemble human tissues already represent significant progress, as described above. However, in some experimental settings, further genetic modification of iPSCs and organoids may be required before downstream applications to address basic biological and biomedical questions [42]. Advances in genome editing technologies make it possible to precisely edit specific genes in iPSCs, modifying them to express or induce specific characteristics.…”

Section: Cutting-edge Technologies For Genetic Modifications Of Ipscs...mentioning

confidence: 99%

“…In general, mutagenesis can take place either in a tissue that serves as a source of adult stem cells or in isolated cells used to generate organoids; the second option is preferable as it is more efficient and less costly. Over the years, attempts have been made to genetically modify different types of ASC-derived organoids, as described in detail by others [13,42]. Schwank et al, Matano et al and Kavasaki et al are just some of the researchers showing that CRISPR/Cas9 could be applied in gastrointestinal tract organoids for gene knock-out or mutation repair [47][48][49].…”

Section: Cutting-edge Technologies For Genetic Modifications Of Ipscs...mentioning

confidence: 99%

See 1 more Smart Citation

Advanced Cellular Models for Rare Disease Study: Exploring Neural, Muscle and Skeletal Organoids

Bombieri,

Corsi,

Trabetti

et al. 2024

IJMS

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Organoids are self-organized, three-dimensional structures derived from stem cells that can mimic the structure and physiology of human organs. Patient-specific induced pluripotent stem cells (iPSCs) and 3D organoid model systems allow cells to be analyzed in a controlled environment to simulate the characteristics of a given disease by modeling the underlying pathophysiology. The recent development of 3D cell models has offered the scientific community an exceptionally valuable tool in the study of rare diseases, overcoming the limited availability of biological samples and the limitations of animal models. This review provides an overview of iPSC models and genetic engineering techniques used to develop organoids. In particular, some of the models applied to the study of rare neuronal, muscular and skeletal diseases are described. Furthermore, the limitations and potential of developing new therapeutic approaches are discussed.

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Section: Cutting-edge Technologies For Genetic Modifications Of Ipscs...mentioning

confidence: 99%

Section: Cutting-edge Technologies For Genetic Modifications Of Ipscs...mentioning

confidence: 99%

Advanced Cellular Models for Rare Disease Study: Exploring Neural, Muscle and Skeletal Organoids

Bombieri,

Corsi,

Trabetti

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Hence, lentiviral transgenesis, CRISPR/Cas9 gene editing, and single-cell readouts were established to study genes function and bring out genetic alterations in organoids. However, the dynamic environment of organoids and their level of complexity also present challenges for genetic editions [ 275 , 276 ].…”

Section: Gene Editing Technologies In Organoidsmentioning

confidence: 99%

Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems

Silva-Pedrosa

Salgado

Ferreira

2023

Cells

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Cellular models have created opportunities to explore the characteristics of human diseases through well-established protocols, while avoiding the ethical restrictions associated with post-mortem studies and the costs associated with researching animal models. The capability of cell reprogramming, such as induced pluripotent stem cells (iPSCs) technology, solved the complications associated with human embryonic stem cells (hESC) usage. Moreover, iPSCs made significant contributions for human medicine, such as in diagnosis, therapeutic and regenerative medicine. The two-dimensional (2D) models allowed for monolayer cellular culture in vitro; however, they were surpassed by the three-dimensional (3D) cell culture system. The 3D cell culture provides higher cell–cell contact and a multi-layered cell culture, which more closely respects cellular morphology and polarity. It is more tightly able to resemble conditions in vivo and a closer approach to the architecture of human tissues, such as human organoids. Organoids are 3D cellular structures that mimic the architecture and function of native tissues. They are generated in vitro from stem cells or differentiated cells, such as epithelial or neural cells, and are used to study organ development, disease modeling, and drug discovery. Organoids have become a powerful tool for understanding the cellular and molecular mechanisms underlying human physiology, providing new insights into the pathogenesis of cancer, metabolic diseases, and brain disorders. Although organoid technology is up-and-coming, it also has some limitations that require improvements.

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“…The emerging technology of personalized “organ on a chip” systems combined with high throughput transcriptomics is an exciting development that may have great relevance for testing and translation of precision therapies (Ronaldson-Bouchard and Vunjak-Novakovic, 2018 ; Ramme et al, 2019 ). Although iPSC-derived systems will not replace animal models for assessing future genetic treatments' safety, inter-species differences in sequence homology will impact targeting strategies and render testing in human-derived models an important part of the translational process (Wang et al, 2021 ).…”

Section: Future Directions For Genome Editing In Ipsc Neuronal Systemsmentioning

confidence: 99%

Genome Editing in iPSC-Based Neural Systems: From Disease Models to Future Therapeutic Strategies

et al. 2021

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Therapeutic advances for neurological disorders are challenging due to limited accessibility of the human central nervous system and incomplete understanding of disease mechanisms. Many neurological diseases lack precision treatments, leading to significant disease burden and poor outcome for affected patients. Induced pluripotent stem cell (iPSC) technology provides human neuronal cells that facilitate disease modeling and development of therapies. The use of genome editing, in particular CRISPR-Cas9 technology, has extended the potential of iPSCs, generating new models for a number of disorders, including Alzheimers and Parkinson Disease. Editing of iPSCs, in particular with CRISPR-Cas9, allows generation of isogenic pairs, which differ only in the disease-causing mutation and share the same genetic background, for assessment of phenotypic differences and downstream effects. Moreover, genome-wide CRISPR screens allow high-throughput interrogation for genetic modifiers in neuronal phenotypes, leading to discovery of novel pathways, and identification of new therapeutic targets. CRISPR-Cas9 has now evolved beyond altering gene expression. Indeed, fusion of a defective Cas9 (dCas9) nuclease with transcriptional repressors or activation domains allows down-regulation or activation of gene expression (CRISPR interference, CRISPRi; CRISPR activation, CRISPRa). These new tools will improve disease modeling and facilitate CRISPR and cell-based therapies, as seen for epilepsy and Duchenne muscular dystrophy. Genome engineering holds huge promise for the future understanding and treatment of neurological disorders, but there are numerous barriers to overcome. The synergy of iPSC-based model systems and gene editing will play a vital role in the route to precision medicine and the clinical translation of genome editing-based therapies.

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Convergence of human pluripotent stem cell, organoid, and genome editing technologies

Cited by 7 publications

References 179 publications

Advanced Cellular Models for Rare Disease Study: Exploring Neural, Muscle and Skeletal Organoids

Advanced Cellular Models for Rare Disease Study: Exploring Neural, Muscle and Skeletal Organoids

Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems

Genome Editing in iPSC-Based Neural Systems: From Disease Models to Future Therapeutic Strategies

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