Aim: To investigate the influence of immune tolerance induced by intrauterine exposure to fetal hepatocytes on liver transplantation in the adult rat.
Methods: LOU/CN rat fetal hepatocytes were injected into the fetuses of pregnant CHN rats (14-16 days of gestation). At 7-9 weeks of age, the surviving male rats received orthotopic liver transplantation (OLT) from male LOU/CN donors and the survival period was observed and monitered by mixed lymphocyte reaction assay and cytotoxicity test.
Results: (1) A total of 31 pregnant CHN rats with 172 fetuses received fetal hepatocytes from LOU/CN rats via intrauterine injection. Among them, thirteen pregnant rats showed normal parturition, with 74 neonatal rats growing up normally. (2) The mean survival period after OLT in rats with fetal exposure to fetal hepatocytes was 32.1+/-3.7 days, which was significantly different from the control (11.8+/-2.3 days, P<0.01) in rats without fetal induction of immune tolerance. (3) Mixed lymphocyte proliferation assays yielded remarkable discrepancies between the groups of rats with- or without fetal exposure to fetal hepatocytes, with values of 8,411+/-1,361 and 22,473+/-1,856 (CPM+/-SD, P<0.01) respectively. (4) Cytotoxicity assays showed values of 21.2+/-6.5 % and 64.5+/-7.2 % (P<0.01) in adult rats with or without fetal induction of immune tolerance.
Conclusion: Intrauterine injection of fetal hepatocytes into rat fetuses can prolong the survival period of liver transplant adult male rats recipients, inducting immune tolerance in OLT.
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http://dx.doi.org/10.3748/wjg.v9.i1.137 | DOI Listing |
Cell Transplant
January 2025
Stem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, China.
Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease characterized by altered levels of inflammatory cytokines. One of the key cytokines involved in the pathogenesis of RA is tumor necrosis factor α (TNF-α), which plays a crucial role in the differentiation of T cells and B cells and serves as a primary trigger of inflammation and joint damage in RA. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have shown potential in alleviating the symptoms of RA.
View Article and Find Full Text PDFGenes Dev
January 2025
Department of Biochemistry, University of Illinois, Urbana-Champaign, Urbana, Illinois 61801, USA;
Hepatocyte polyploidy and maturity are critical to acquiring specialized liver functions. Multiple intracellular and extracellular factors influence ploidy, but how they cooperate temporally to steer liver polyploidization and maturation or how post-transcriptional mechanisms integrate into these paradigms is unknown. Here, we identified an important regulatory hierarchy in which postnatal activation of epithelial splicing regulatory protein 2 (ESRP2) stimulates processing of liver-specific microRNA () to facilitate polyploidization, maturation, and functional competence of hepatocytes.
View Article and Find Full Text PDFAJP Rep
January 2025
Department of Pediatric Hematology-Oncology, Cooper Medical School of Rowan University, Camden, New Jersey.
Gestational alloimmune liver disease (GALD) is characterized by maternal IgG-directed fetal hepatocyte damage and can lead to severe liver failure and fetal or infant death. Moreover, GALD is associated with a near 90% risk of recurrence in subsequent pregnancies. We present a case of a newborn patient delivered to a 32-year-old G2P1000 mother who received prolonged antenatal intravenous immunoglobulin (IVIG) treatment during the current pregnancy due to the neonatal death of the first child from GALD-related liver failure.
View Article and Find Full Text PDFStem Cell Res Ther
December 2024
Department of Pediatrics, Qilu Hospital of Shandong University, 107 Wenhua Xilu, Jinan, 250012, Shandong, P.R. China.
Background: Hepatic organoids (HOs), validated through comparative sequencing with human liver tissues, are reliable models for liver research. Comprehensive transcriptomic and proteomic sequencing of HOs throughout their induction period will enhance the platform's utility, aiding in the elucidation of liver development's molecular mechanisms.
Methods: We developed hepatic organoids (HOs) from embryonic stem cells (ESCs) through a de novo induction protocol, mimicking the stages of fetal liver development: ESCs to definitive endoderm (DE), then to foregut (FG), hepatoblasts (HB), and finally to HOs stage 1 (HO1), culminating in self-organizing HOs stage 2 (HO2) via dissociation and re-inoculation.
Cell Mol Biol Lett
December 2024
Department of Endocrinology, Peking University First Hospital, No. 8 Xishiku Ave, Xicheng, Beijing, 100034, People's Republic of China.
Background: Maternal overnutrition, prevalent among women of childbearing age, significantly impacts offspring health throughout their lifetime. While DNA methylation of metabolic-related genes mediates the transmission of detrimental effects from maternal high-fat diet (HFD), its role in programming hepatic cholesterol metabolism in offspring, particularly during weaning, remains elusive.
Methods: Female C57BL/6 J mice were administered a HFD or control diet, before and during, gestation and lactation.
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