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Cited by 411Pluripotent Stem Cells ResearchCRISPR and Genetic EngineeringNeurogenesis and neuroplasticity mechanisms

Technical Challenges in Using Human Induced Pluripotent Stem Cells to Model Disease

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Saha, Krishanu, Jaenisch, Rudolf·2009·Cell Stem Cell
DOI 10.1016/j.stem.2009.11.009PMC PMC2921621
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Abstract

Reprogramming of human somatic cells uses readily accessible tissue, such as skin or blood, to generate embryonic-like induced pluripotent stem cells (iPSCs). This procedure has been applied to somatic cells from patients who are classified into a disease group, thus creating "disease-specific" iPSCs. Here, we examine the challenges and assumptions in creating a disease model from a single cell of the patient. Both the kinetics of disease onset and progression as well as the spatial localization of disease in the patient's body are challenges to disease modeling. New tools in genetic modification, reprogramming, biomaterials, and animal models can be used for addressing these challenges.

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  • Reprogramming without viral integration using plasmids or direct reprogramming protein delivery assays can solve the oncogene issue.

    “Nonetheless, reprogramming without viral integration with plasmids or direct reprogramming protein delivery assays can solve this issue [98,99].”

    From Non-Integrating Lentiviral Vectors in Clinical Applications: A Glance Through (2022) · cites this paper as [99]

    In “Strategies of deriving reprogramming factor-free hiPSCs” (page unavailable), the paper links integrated reprogramming factors, including c-Myc, to potential harm and describes plasmid and protein-based approaches that avoid or reduce genetic modification. But it says plasmid methods cannot completely rule out vector-fragment integration and protein transfection is exceedingly inefficient, so it does not establish that these methods solve the oncogene issue. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Stem cell models have faced inherent constraints in recapitulating in vivo cellular diversity and the organization of neuronal-glial interactions.

    “Despite advances in modeling Ts21, murine systems have limited translational relevance to human-specific aspects of neurodevelopment and cortical circuitry (7), whereas stem cell models have faced inherent constraints in recapitulating in vivo cellular diversity and the organization of neuronal-glial interactions (8, 9).”

    From Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex (2026) · cites this paper as [8]

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Cited by

Sorted by citations

Authors
Saha, K., & Jaenisch, R.
Affiliations
Whitehead Institute for Biomedical Research (US)
Corresponding author
Jaenisch, Rudolf
ORCID
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2009-12
Volume
5
Issue
6
Pages
584-595
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
DOI
10.1016/j.stem.2009.11.009
PMC
PMC2921621
OpenAlex
W2101736621
Cited by
411
References
6
Citations by year
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FWCI
3.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Funders
  • National Institutes of Health (2r01ca084198-10)
  • U.S. Public Health Service (R01-HDO45022)
  • National Cancer Institute (R01-CA084198, R01CA087869, R37CA084198)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD045022)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
human induced pluripotent stem cells, disease modeling, somatic cell reprogramming, disease onset and progression, genetic modification, biomaterials, animal models, patient-derived iPSCs
MeSH terms
Animals, Cell Differentiation, Disease Models, Animal, Humans, Cell Culture Techniques, Genomics, Induced Pluripotent Stem Cells

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