In vitro differentiation of human intestinal organoids (HIOs) from pluripotent stem cells is an unparalleled system for creating complex, multicellular three-dimensional structures capable of giving rise to tissue analogous to native human tissue. Current methods for generating HIOs rely on growth in an undefined tumour-derived extracellular matrix (ECM), which severely limits the use of organoid technologies for regenerative and translational medicine. Here, we developed a fully defined, synthetic hydrogel based on a four-armed, maleimide-terminated poly(ethylene glycol) macromer that supports robust and highly reproducible in vitro growth and expansion of HIOs, such that three-dimensional structures are never embedded in tumour-derived ECM. We also demonstrate that the hydrogel serves as an injection vehicle that can be delivered into injured intestinal mucosa resulting in HIO engraftment and improved colonic wound repair. Together, these studies show proof-of-concept that HIOs may be used therapeutically to treat intestinal injury.
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http://dx.doi.org/10.1038/ncb3632 | DOI Listing |
Proc Natl Acad Sci U S A
February 2025
State Key Laboratory of Genetic Engineering, School of Life Sciences, Liver Cancer Institute of Zhongshan Hospital, Fudan University, Shanghai 200438, China.
Aging is a complex process that affects multiple organs, and the discovery of a pharmacological approach to ameliorate aging is considered the Holy Grail of medicine. Here, we performed an N-ethyl-N-nitrosourea forward genetic screening in zebrafish and identified an accelerated aging mutant named (), harboring a mutation in the - () gene. Loss of leads to a short lifespan and age-related characteristics in the intestine of zebrafish embryos, such as cellular senescence, genomic instability, and epigenetic alteration.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Radiation Physics, Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
Accurate and efficient automatic segmentation is essential for various clinical tasks such as radiotherapy treatment planning. However, atlas-based segmentation still faces challenges due to the lack of representative atlas dataset and the computational limitations of deformation algorithms. In this work, we have proposed an atlas selection procedure (subset atlas grouping approach, MAS-SAGA) which utilized both image similarity and volume features for selecting the best-fitting atlases for contour propagation.
View Article and Find Full Text PDFInt J Colorectal Dis
January 2025
Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Palle Juul-Jensens, Boulevard 99, 8200, Aarhus N, Denmark.
Purpose: Functional faecal incontinence (FFI) is a stigmatising condition for a child and parents and can be a challenge to treat even in tertiary centres. Transanal irrigation (TAI) is an emerging treatment with great success in refractory cases. We performed TAI with a substantially decreased amount of water used (low-volume TAI), yet no previous evidence exists on this treatment in children.
View Article and Find Full Text PDFInflamm Res
January 2025
Department of Biochemistry, Cancer Biology, Neuroscience, and Pharmacology, School of Medicine, Meharry Medical College, 1005 D.B. Todd Jr. Blvd, Nashville, TN, USA.
Background: The aberrant expression of α defensin 5 (DEFA5) protein in colonic inflammatory bowel diseases (IBDs) underlies the distinct pathogenesis of Crohn's colitis (CC). It can serve as a biomarker for differentiating CC from Ulcerative colitis (UC), particularly in Indeterminate colitis (IC) cases into UC and CC. We evaluated the specificity of commercially available anti-DEFA5 antibodies, emphasizing the need to further validate their appropriateness for a given application and highlighting the necessity for novel antibodies.
View Article and Find Full Text PDFGut Microbes
December 2025
Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Ischemia-reperfusion injury (IRI) is a major obstacle in liver transplantation, especially with steatotic donor livers. Dysbiosis of the gut microbiota has been implicated in modulating IRI, and plays a pivotal role in regulating host inflammatory and immune responses, but its specific role in liver transplantation IRI remains unclear. This study explores whether can mitigate IRI and its underlying mechanisms.
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