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Generation of tissue-engineered small intestine using embryonic stem cell-derived human intestinal organoids
Open accessAbstract
Short bowel syndrome (SBS) is characterized by poor nutrient absorption due to a deficit of healthy intestine. Current treatment practices rely on providing supportive medical therapy with parenteral nutrition; while life saving, such interventions are not curative and are still associated with significant co-morbidities. As approaches to lengthen remaining intestinal tissue have been met with only limited success and intestinal transplants have poor survival outcomes, new approaches to treating SBS are necessary. Human intestine derived from embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs), called human intestinal organoids (HIOs), have the potential to offer a personalized and scalable source of intestine for regenerative therapies. However, given that HIOs are small three-dimensional structures grown in vitro, methods to generate usable HIO-derived constructs are needed. We investigated the ability of hESCs or HIOs to populate acellular porcine intestinal matrices and artificial polyglycolic/poly L lactic acid (PGA/PLLA) scaffolds, and examined the ability of matrix/scaffolds to thrive when transplanted in vivo. Our results demonstrate that the acellular matrix alone is not sufficient to instruct hESC differentiation towards an endodermal or intestinal fate. We observed that while HIOs reseed acellular porcine matrices in vitro, the HIO-reseeded matrices do not thrive when transplanted in vivo. In contrast, HIO-seeded PGA/PLLA scaffolds thrive in vivo and develop into tissue that looks nearly identical to adult human intestinal tissue. Our results suggest that HIO-seeded PGA/PLLA scaffolds are a promising avenue for developing the mucosal component of tissue engineered human small intestine, which need to be explored further to develop them into fully functional tissue.
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“However, pre-differentiated HIOs were able to seed onto decellularized porcine intestinal ECM and form correct spatial orientation-mimicking intestine79.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [79]
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“Finkbeiner and colleagues found that undifferentiated human embryonic stem cells (ESCs) could not directly differentiate into HIOs in a decellularized porcine intestinal ECM.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [79]
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Metadata
- Authors
- Finkbeiner, S. R., Freeman, J. J., Wieck, M. M., El-Nachef, W., Altheim, C. H., Tsai, Y.-H., Huang, S., Dyal, R., White, E. S., Grikscheit, T. C., Teitelbaum, D. H., & Spence, J. R.
- Affiliations
- University of Michigan (US)
- Children's Hospital Los Angeles (US)
- Corresponding author
- Spence, Jason R.
- ORCID
- Venue
- Biology Open
- Publisher
- The Company of Biologists
- Published
- 2015-10-12
- Volume
- 4
- Issue
- 11
- Pages
- 1462-1472
- ISSN
- 2046-6390 (ISSN-L)
- PMC
- PMC4728347
- OpenAlex
- W2261291226
- Cited by
- 174
- References
- 82
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 7 · 2023: 12 · 2022: 17 · 2021: 24 · 2020: 31 · 2019: 20 · 2018: 18 · 2017: 20 · 2016: 10
- FWCI
- 16.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Biology Open (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- California Institute for Regenerative Medicine (RN3-06425)
- Hartwell Foundation
- National Institutes of Health (UL1TR000433, DK034933)
- Harvard Stem Cell Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK085532, P30DK034933, DK 034933, K01DK091415, U01DK085532, U01DK103141, T32DK094775)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007505)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- human intestinal organoids, embryonic stem cells, short bowel syndrome, intestinal regeneration, in vivo transplantation
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