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Homogeneous and organized differentiation within embryoid bodies induced by microsphere-mediated delivery of small molecules
Open accessAbstract
Cell specification and tissue formation during embryonic development are precisely controlled by the local concentration and temporal presentation of morphogenic factors. Similarly, pluripotent embryonic stem cells can be induced to differentiate in vitro into specific phenotypes in response to morphogen treatment. Embryonic stem cells (ESCs) are commonly differentiated as 3D spheroids referred to as embryoid bodies (EBs); however, differentiation of cells within EBs is typically heterogeneous and disordered. In this study, we demonstrate that in contrast to soluble morphogen treatment, delivery of morphogenic factors directly within EB microenvironments in a spatiotemporally controlled manner using polymer microspheres yields homogeneous, synchronous and organized ESC differentiation. Degradable PLGA microspheres releasing retinoic acid were incorporated directly within EBs and induced the formation of cystic spheroids uniquely resembling the phenotype and structure of early streak mouse embryos (E6.75), with an exterior of FOXA2+ visceral endoderm enveloping an epiblast-like layer of OCT4+ cells. These results demonstrate that controlled morphogen presentation to stem cells using degradable microspheres more efficiently directs cell differentiation and tissue formation than simple soluble delivery methods and presents a unique route to study the spatiotemporal effects of morphogenic factors on embryonic developmental processes in vitro.
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“The spatiotemporal release of RA by polymeric microparticles incorporated within embryonic bodies, derived from human embryonic stem cells, was reported to induce cell differentiation and tissue formation resembling the phenotype and structure of early human embryos7.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [7]
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Metadata
- Authors
- Carpenedo, R. L., Bratt-Leal, A. M., Marklein, R. A., Seaman, S. A., Bowen, N. J., McDonald, J. F., & McDevitt, T. C.
- Affiliations
- Georgia Institute of Technology (US)
- Corresponding author
- McDevitt, Todd C.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 30
- Issue
- 13
- Pages
- 2507-2515
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC2921510
- OpenAlex
- W2071071731
- Cited by
- 133
- References
- 53
- Citations by year
- 2026: 1 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 9 · 2019: 6 · 2018: 9 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 10 · 2013: 18 · 2012: 14
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- National Institute of General Medical Sciences (T32GM008433)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- embryoid bodies, embryonic stem cell differentiation, polymer microspheres, PLGA microspheres, retinoic acid, visceral endoderm, epiblast-like cells, FOXA2, Oct4, embryonic development, tissue formation
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Microscopy, Electron, Scanning, Microspheres, Tretinoin, Gene Expression Profiling, Mice, Embryonic Stem Cells
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