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Maternal and Donor Human Milk Support Robust Intestinal Epithelial Growth and Differentiation in a Fetal Intestinal Organoid Model
Maternal and Donor Human Milk Support Robust Intestinal Epithelial Growth and Differentiation in a Fetal Intestinal Organoid Model
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151102
- ISBN
- 9798382327686
- DDC
- 610
- 저자명
- Smith, Lauren.
- 서명/저자
- Maternal and Donor Human Milk Support Robust Intestinal Epithelial Growth and Differentiation in a Fetal Intestinal Organoid Model
- 발행사항
- [Sl] : Yale University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 60 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
- 주기사항
- Advisor: Konnikova, Liza.
- 학위논문주기
- Thesis (D.Med.)--Yale University, 2024.
- 초록/해제
- 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.
- 일반주제명
- Medicine
- 일반주제명
- Biochemistry
- 일반주제명
- Bioengineering
- 일반주제명
- Obstetrics
- 키워드
- Maternal milk
- 기타저자
- Yale University Yale School of Medicine
- 기본자료저록
- Dissertations Abstracts International. 85-11B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798382327686
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a610
■1001 ▼aSmith, Lauren.
■24510▼aMaternal and Donor Human Milk Support Robust Intestinal Epithelial Growth and Differentiation in a Fetal Intestinal Organoid Model
■260 ▼a[Sl]▼bYale University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a60 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-11, Section: B.
■500 ▼aAdvisor: Konnikova, Liza.
■5021 ▼aThesis (D.Med.)--Yale University, 2024.
■520 ▼aNecrotizing 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.
■590 ▼aSchool code: 0265.
■650 4▼aMedicine
■650 4▼aBiochemistry
■650 4▼aBioengineering
■650 4▼aObstetrics
■653 ▼aHydrolyzed formula
■653 ▼aEpithelial growth
■653 ▼aNecrotizing enterocolitis
■653 ▼aIntestinal organoids
■653 ▼aMaternal milk
■690 ▼a0564
■690 ▼a0202
■690 ▼a0487
■690 ▼a0380
■71020▼aYale University▼bYale School of Medicine.
■7730 ▼tDissertations Abstracts International▼g85-11B.
■790 ▼a0265
■791 ▼aD.Med.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160695▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
