scholarly journals Ectopic hepatocyte transplantation cures the pig model of tyrosinemia

2019 ◽  
Author(s):  
Clara T Nicolas ◽  
Raymond D Hickey ◽  
Kari L Allen ◽  
Zeji Du ◽  
Caitlin J VanLith ◽  
...  
Keyword(s):  
Liver Disease ◽  
Lymph Nodes ◽  
Liver Failure ◽  
Pig Model ◽  
Hepatocyte Transplantation ◽  
Large Animal ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Metabolic Liver Disease ◽  
Diseased Liver

AbstractThe effectiveness of cell-based therapies to treat liver failure is limited by the diseased liver environment. Herein we provide preclinical proof-of-concept for the treatment of liver failure through hepatocyte transplantation into lymph nodes in a large-animal model of hereditary tyrosinemia type 1 (HT1), a metabolic liver disease caused by deficiency of fumarylacetoacetate hydrolase (FAH) enzyme. FAH-deficient pigs received autologous hepatocyte transplantation into mesenteric lymph nodes after ex vivo transduction with a lentiviral vector carrying the pig Fah gene. Hepatocytes showed early (6 hour) and durable (8 month) engraftment in lymph nodes, with reproduction of vascular and hepatic microarchitecture. Subsequently, hepatocytes migrated to and repopulated the native diseased liver. The corrected cells generated enough liver mass to clinically ameliorate disease as early as 97 days post-transplantation, with complete normalization of tyrosine levels and liver function tests. Integration site analysis defined the corrected hepatocytes in the liver as a subpopulation of hepatocytes in the lymph nodes, indicating that the lymph nodes served as a source for healthy hepatocytes to repopulate a diseased liver. Ectopic transplantation of hepatocytes cures the pig model of HT1 and presents a promising approach to the treatment of liver disease in patients with pre-existing liver damage and fibrosis.One Sentence SummaryTransplantation of corrected hepatocytes in mesenteric lymph nodes can cure fatal metabolic liver disease by providing organized liver tissue and by repopulating the diseased liver in the pig tyrosinemia model.

scholarly journals Fulminant Liver Failure with Necrotizing Foci in the Liver, Spleen and Lymph Nodes in Celiac Disease Due to Malignant Lymphoma

1996 ◽  
Vol 10 (4) ◽  
pp. 225-229 ◽  
Author(s):  
Hugh James Freeman
Keyword(s):  
Celiac Disease ◽  
T Cell ◽  
Lymph Nodes ◽  
Liver Failure ◽  
Cell Receptor ◽  
Lymphoid Cells ◽  
Mesenteric Lymph Nodes ◽  
Rare Type ◽  
Mesenteric Lymph ◽  
Spleen And Lymph Nodes

A 65-year-old female with celiac disease developed cholestatic jaundice and fatal liver failure. Investigations revealed widespread necrotic foci in the liver, spleen and mesenteric lymph nodes, changes reminiscent of the mesenteric lymph node cavitation syndrome, which is known to complicate celiac disease. In addition, malignant lymphoid cells were present infiltrating hepatic sinusoids, lymph nodes and spleen. These features are typical of hepatosplenic lymphoma, a rare type of peripheral T cell lymphoma with T cell receptor rearrangement. Lymphorecticular malignancy complicating celiac disease may present with fulminant liver disease.

In situ demonstration of migration of dendritic cells released from rat small intestine to mesenteric lymph nodes

2001 ◽  
Vol 120 (5) ◽  
pp. A183-A183
Author(s):  
H KOBAYASHI ◽  
H NAGATA ◽  
S MIURA ◽  
T AZUMA ◽  
H SUZUKI ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Small Intestine ◽  
Lymph Nodes ◽  
Rat Small Intestine ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph

Mesenteric lymph nodes in children: what is normal?

2007 ◽  
Vol 2007 ◽  
pp. 166-168 ◽  
Author(s):  
A.E. Oestreich
Keyword(s):  
Lymph Nodes ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph

Clinical Significance of Mesenteric Lymph Nodes Detected on Postoperative CT after a Total Pharyngolaryngectomy and Reconstruction with a Jejunal Free Flap

2008 ◽  
Vol 58 (2) ◽  
pp. 113
Author(s):  
Sun Mi Kim ◽  
Jeong Hyun Lee ◽  
Jin Woo Choi ◽  
Byung Se Choi ◽  
Kyung Soon Jeong ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Clinical Significance ◽  
Free Flap ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Total Pharyngolaryngectomy

scholarly journals The microbiota is dispensable for the early stages of peripheral regulatory T cell induction within mesenteric lymph nodes

2021 ◽  
Author(s):  
Carolin Wiechers ◽  
Mangge Zou ◽  
Eric Galvez ◽  
Michael Beckstette ◽  
Maria Ebel ◽  
...  
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Regulatory T Cell ◽  
De Novo ◽  
Bacterial Species ◽  
Short Chain Fatty Acids ◽  
Mesenteric Lymph Nodes ◽  
Direct Role ◽  
Early Stages ◽  
Mesenteric Lymph

AbstractIntestinal Foxp3+ regulatory T cell (Treg) subsets are crucial players in tolerance to microbiota-derived and food-borne antigens, and compelling evidence suggests that the intestinal microbiota modulates their generation, functional specialization, and maintenance. Selected bacterial species and microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), have been reported to promote Treg homeostasis in the intestinal lamina propria. Furthermore, gut-draining mesenteric lymph nodes (mLNs) are particularly efficient sites for the generation of peripherally induced Tregs (pTregs). Despite this knowledge, the direct role of the microbiota and their metabolites in the early stages of pTreg induction within mLNs is not fully elucidated. Here, using an adoptive transfer-based pTreg induction system, we demonstrate that neither transfer of a dysbiotic microbiota nor dietary SCFA supplementation modulated the pTreg induction capacity of mLNs. Even mice housed under germ-free (GF) conditions displayed equivalent pTreg induction within mLNs. Further molecular characterization of these de novo induced pTregs from mLNs by dissection of their transcriptomes and accessible chromatin regions revealed that the microbiota indeed has a limited impact and does not contribute to the initialization of the Treg-specific epigenetic landscape. Overall, our data suggest that the microbiota is dispensable for the early stages of pTreg induction within mLNs.

Pericolic mesenteric lymph nodes: an aid in distinguishing diverticulitis from cancer of the colon.

1997 ◽  
Vol 169 (5) ◽  
pp. 1253-1255 ◽  
Author(s):  
K N Chintapalli ◽  
C C Esola ◽  
S Chopra ◽  
A A Ghiatas ◽  
G D Dodd
Keyword(s):  
Lymph Nodes ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph

Effects of zearalenone-induced oxidative stress and Keap1–Nrf2 signaling pathway-related gene expression in the ileum and mesenteric lymph nodes of post-weaning gilts

Toxicology ◽  
2020 ◽  
Vol 429 ◽  
pp. 152337 ◽  
Author(s):  
Qun Cheng ◽  
Shuzhen Jiang ◽  
Libo Huang ◽  
Yuxi Wang ◽  
Weiren Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Lymph Nodes ◽  
Signaling Pathway ◽  
Related Gene ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Nrf2 Signaling Pathway

Mesenteric lymph nodes in children: what is normal?

2005 ◽  
Vol 35 (8) ◽  
pp. 774-777 ◽  
Author(s):  
Boaz Karmazyn ◽  
Elizabeth A. Werner ◽  
Babak Rejaie ◽  
Kimberly E. Applegate
Keyword(s):  
Lymph Nodes ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph

scholarly journals Culture-Independent Analysis of Indomethacin-Induced Alterations in the Rat Gastrointestinal Microbiota

2006 ◽  
Vol 72 (10) ◽  
pp. 6707-6715 ◽  
Author(s):  
Andrew B. Dalby ◽  
Daniel N. Frank ◽  
Allison L. St. Amand ◽  
Alison M. Bendele ◽  
Norman R. Pace
Keyword(s):  
Small Intestine ◽  
Lymph Nodes ◽  
Small Subunit ◽  
Rrna Genes ◽  
Small Subunit Rrna ◽  
Mesenteric Lymph Nodes ◽  
Gastrointestinal Microbiota ◽  
Mesenteric Lymph ◽  
Independent Analysis ◽  
Culture Independent

ABSTRACT Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for a variety of inflammatory conditions; however, the benefits of this class of drugs are accompanied by deleterious side effects, most commonly gastric irritation and ulceration. NSAID-induced ulceration is thought to be exacerbated by intestinal microbiota, but previous studies have not identified specific microbes that contribute to these adverse effects. In this study, we conducted a culture-independent analysis of ∼1,400 bacterial small-subunit rRNA genes associated with the small intestines and mesenteric lymph nodes of rats treated with the NSAID indomethacin. This is the first molecular analysis of the microbiota of the rat small intestine. A comparison of clone libraries and species-specific quantitative PCR results from rats treated with indomethacin and untreated rats revealed that organisms closely related to Enterococcus faecalis were heavily enriched in the small intestine and mesenteric lymph nodes of the treated rats. These data suggest that treatment of NSAID-induced ulceration may be facilitated by addressing the microbiological imbalances.

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