Multi-lineage human iPSC-derived platforms for disease modeling and drug discovery
Open accessAbstract
Human induced pluripotent stem cells (hiPSCs) provide a powerful platform for disease modeling and have unlocked new possibilities for understanding the mechanisms governing human biology, physiology, and genetics. However, hiPSC-derivatives have traditionally been utilized in two-dimensional monocultures, in contrast to the multi-systemic interactions that influence cells in the body. We will discuss recent advances in generating more complex hiPSC-based systems using three-dimensional organoids, tissue-engineering, microfluidic organ-chips, and humanized animal systems. While hiPSC differentiation still requires optimization, these next-generation multi-lineage technologies can augment the biomedical researcher's toolkit and enable more realistic models of human tissue function.
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Astrocyte and microglia iPSC models partially recapitulate the transcriptomes of their in vivo counterparts and may capture authentic neurodegenerative disease phenotypes.
“Astrocyte and microglia iPSC models partially recapitulate the transcriptomes of their in vivo counterparts and may capture authentic neurodegenerative disease phenotypes [345,406,480,481,482,483,484].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [483]
The Introduction’s section on hiPSC-derived assembloids (page unavailable) says multi-lineage models have been used to study neural–glial interplay in Alzheimer’s disease, supporting the possibility of modeling neurodegenerative disease. But neither that section nor the transcriptomics discussion establishes that iPSC-derived astrocytes and microglia partially recapitulate the transcriptomes of their in vivo counterparts; the Conclusions also caution that hiPSC-derived tissues have not been shown to be transcriptionally identical to adult tissue. (LLM, conf=0.84)
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- Authors
- Sharma, A., Sances, S., Workman, M. J., & Svendsen, C. N.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Svendsen, Clive N.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 26
- Issue
- 3
- Pages
- 309-329
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC7159985
- OpenAlex
- W3010518562
- Cited by
- 296
- References
- 266
- Citations by year
- 2026: 29 · 2025: 46 · 2024: 55 · 2023: 50 · 2022: 49 · 2021: 45 · 2020: 22
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1UG3TR003148, 5UG3NS105703, T32 HL116273, 12879)
- Paul G. Allen Family Foundation
- Amyotrophic Lateral Sclerosis Association
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- human induced pluripotent stem cells, disease modeling, drug discovery, multilineage differentiation, three-dimensional organoids, tissue engineering, humanized animal models
- MeSH terms
- Animals, Cell Differentiation, Humans, Organoids, Tissue Engineering, Drug Discovery, Induced Pluripotent Stem Cells
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