scholarly journals Development of Ectopic Livers by Hepatocyte Transplantation Into Swine Lymph Nodes

2020 ◽  
Vol 26 (12) ◽  
pp. 1629-1643 ◽  
Author(s):  
Paulo Fontes ◽  
Junji Komori ◽  
Roberto Lopez ◽  
Wallis Marsh ◽  
Eric Lagasse

2019 ◽  
Author(s):  
Clara T Nicolas ◽  
Raymond D Hickey ◽  
Kari L Allen ◽  
Zeji Du ◽  
Caitlin J VanLith ◽  
...  

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.



Author(s):  
O. Faroon ◽  
F. Al-Bagdadi ◽  
T. G. Snider ◽  
C. Titkemeyer

The lymphatic system is very important in the immunological activities of the body. Clinicians confirm the diagnosis of infectious diseases by palpating the involved cutaneous lymph node for changes in size, heat, and consistency. Clinical pathologists diagnose systemic diseases through biopsies of superficial lymph nodes. In many parts of the world the goat is considered as an important source of milk and meat products.The lymphatic system has been studied extensively. These studies lack precise information on the natural morphology of the lymph nodes and their vascular and cellular constituent. This is due to using improper technique for such studies. A few studies used the SEM, conducted by cutting the lymph node with a blade. The morphological data collected by this method are artificial and do not reflect the normal three dimensional surface of the examined area of the lymph node. SEM has been used to study the lymph vessels and lymph nodes of different animals. No information on the cutaneous lymph nodes of the goat has ever been collected using the scanning electron microscope.



Author(s):  
F.E. Hossler ◽  
M.I. McKamey ◽  
F.C. Monson

A comprehensive study of the microvasculature of the normal rabbit bladder, revealed unusual "capillary glomeruli" along the lateral walls. Here they are characterized as hemal lymph nodes using light microscopy, SEM, TEM, ink injection, and vascular casting.Bladders were perfused via a cannula placed in the abdominal aorta with either 2% glutaraldehyde in 0.1M cacodylate buffer (pH 7.4) for fixation, 10% India ink in 0.9% saline and 0.1M phosphate (pH 7.4) for vessel tracing, or resin (Mercoximethylmethacrylate: catalyst, 4:1:0.3; Ladd Research Industries) for vascular corrosion casting. Infusion pressure was 100mm Hg. Fixed tissue was sectioned from epon-araldyte resin, and stained with toluidine blue for light microscopy, and lead and uranium for TEM. Ink injected tissue was photographed directly from saline-filled bladders illuminated from below. Resin-filled tissue was macerated in 5% KOH and distilled water. Casts were critical point dried, sputter coated with goldpalladium, and examined by routine SEM at 10 KV.



2001 ◽  
Vol 120 (5) ◽  
pp. A183-A183
Author(s):  
H KOBAYASHI ◽  
H NAGATA ◽  
S MIURA ◽  
T AZUMA ◽  
H SUZUKI ◽  
...  


2004 ◽  
Vol 171 (4S) ◽  
pp. 228-228
Author(s):  
Martin Schumacher ◽  
Fiona C. Burkhard ◽  
Regula Markwalder ◽  
Urs E. Studer


2004 ◽  
Vol 171 (4S) ◽  
pp. 83-83
Author(s):  
Amir Sherif ◽  
Ulrike Garske ◽  
Manuel De La Torre ◽  
Per-Uno Malmstrom ◽  
Magnus Thorn


JAMA ◽  
1965 ◽  
Vol 194 (1) ◽  
pp. 1-4 ◽  
Author(s):  
A. D. Nicastri




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