ABSTRACT
BACKGROUND: Animals can play an important role in preparing tissues for human through the development of xenotransplantation protocols. The most common problem with liver transplantation like any other organ transplantation is organ supply shortage. OBJECTIVE: To evaluate the in utero xenotransplantation of mouse bone marrow-derived stromal/stem cells (BMSCs) to the liver of rat fetus to produce mouse liver tissue. MATERIALS AND METHODS: BMSCs were isolated and confirmed from enhanced green fluorescent protein (eGFP)-genetic labeled mice. Using a microinjection protocol, mice BMSCs were injected into the liver of rat fetuses in utero on day 14 of pregnancy. After birth, livers were collected and the presence of mice eGFP-positive cells in rat livers was evaluated through polymerase chain reaction. RESULTS: The eGFP mRNA was detected in the liver of injected infant rats. BMSCs of adult mice were capable to remain functional probably as hepatocyte-like cells in liver of infant rats after in utero xenotransplantation. CONCLUSION: BMSCs have the potential for intrauterine xenotransplantation for the treatment of liver dysfunction before birth. This method can also be used for xenoproduction of liver tissue for transplantation.
ABSTRACT
Gallstone disease (GD) is highly correlated with metabolic syndrome and its related illnesses including type II diabetes (DMII) and polycystic ovary syndrome (PCOS). While previous studies claimed that metformin decreases the chance of developing GD in PCOS patients, this phenomenon has not been investigated in animal models to date. Here we fed a high fat diet (HFD) containing 2% of cholesterol and 1% of cholic acid to ten-week-old male C57Bl/6 mice for 105 days. The groups were as follows: Low fat diet; HFD; HFD +â¯Ursodeoxycholic acid (UDCA) (day 1-105); HFD +â¯Metformin (day 1-105); HFD +â¯Metformin (Met) (day 64-105). All drugs were administered by oral gavage (Met = 300â¯mg/kg & UDCA = 750â¯mg/kg). Serum lipid profile and gross organ examination were performed after euthanasia. A microscopic evaluation of the paraffin-embedded gallbladders was done after hematoxylin & eosin and Von Kossa staining. HFD successfully induces gallstone (4 out of 4 of the HFD members). While both UDCA and metformin (d 1-105) prevented gallstone formation and cholecystitis, Metformin (d 64-105) group had a few small stones. Additionally, metformin induces mucosal calcification in gallbladder (porcelain GB) of more than 80% of the HFD +â¯Met (day 1-105) and HFD +â¯Met (day 64-105) groups, collectively, which can be a potential problem by itself. While metformin shows a noticeable benefit towards GB health by reducing the chance for gallstone formation, if it induces porcelain gallbladder in humans as well, it might inflict patients with preventable medical charges.
