자료유형  

 학위논문

Control Number  

0017160695

International Standard Book Number  

9798382327686

Dewey Decimal Classification Number  

610

Main Entry-Personal Name  

Smith, Lauren.

Publication, Distribution, etc. (Imprint  

[S.l.] : Yale University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

60 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-11, Section: B.

General Note  

Advisor: Konnikova, Liza.

Dissertation Note  

Thesis (D.Med.)--Yale University, 2024.

Summary, Etc.  

요약Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using small intestinal organoids derived from fetal tissue of a gestational age similar to an extremely preterm infant, this study aims to assess the effect of diet on intestinal epithelial growth and differentiation to elucidate the role nutrition type plays in intestinal development and modifies the risk for NEC.  Organoids were cultured for 5 days in organoid growth media and 5 days in organoid differentiation media supplemented 1:40 with four different diet conditions: maternal milk (MM), donor human milk (DHM), standard formula (SF), or extensively hydrolyzed formula (HF). 4x images were captured daily and organoids were quantified via manual counting and measurement. Organoids from both the growth and differentiation phase were preserved for RNA bulk sequencing and immunofluorescence staining with Ki67, chromogranin A, and cleaved caspase 3. Media was saved from day 5 of growth and differentiation for cytokine and growth factor analysis.Human milk supplementation improved growth and differentiation of fetal intestinal organoids generating larger organoids during the growth phase and organoids with longer and wider buds during differentiation compared to formula. Ki67 staining confirmed the proliferative nature of milk-supplemented organoids and chromogranin A staining proved that MM-supplemented organoids induced highest enteroendocrine differentiation. Human milk supplementation also upregulated genes involved in proliferation and promoted a homeostatic immune landscape while those supplemented with formula had a downregulation of cell-cycle-promoting genes and a more inflammatory immune signature. Our results show that MM, and to a lesser extent DHM, support robust intestinal epithelial proliferation and differentiation, suggesting a critical role for factors enriched in human milk in intestinal epithelial health.

Subject Added Entry-Topical Term  

Medicine.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Bioengineering.

Subject Added Entry-Topical Term  

Obstetrics.

Index Term-Uncontrolled  

Hydrolyzed formula

Index Term-Uncontrolled  

Epithelial growth

Index Term-Uncontrolled  

Necrotizing enterocolitis

Index Term-Uncontrolled  

Intestinal organoids

Index Term-Uncontrolled  

Maternal milk

Added Entry-Corporate Name  

Yale University Yale School of Medicine

Host Item Entry  

Dissertations Abstracts International. 85-11B.

Electronic Location and Access  

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Control Number  

joongbu:657955