Liver organoids in domestic animals: an expected promise for metabolic studies

Baquerre, Camille; Montillet, Guillaume; Pain, Bertrand

doi:10.1186/s13567-021-00916-y

Cited by 7 publications

(3 citation statements)

References 64 publications

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“…Minor cell populations include hepatic stellate cells, cells of the sinusoidal endothelium, Kupffer cells, specialized hepatic natural killer cells and itinerant leukocytes [19,20]. Hepatic organoids from several species have been generated previously, including humans, mice, dogs, pigs, cats, chickens and trout [21][22][23][24][25][26][27][28][29], either from biopsy specimens containing hepatic progenitor cells or from pluripotent stem cells. Protocols for the establishment of hepatic organoids from rabbits have not yet been published.…”

Section: Introductionmentioning

confidence: 99%

Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses

Kardia

Fakhri

Pavy

et al. 2023

Journal of General Virology

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The genus Lagovirus of the family Caliciviridae contains some of the most virulent vertebrate viruses known. Lagoviruses infect leporids, such as rabbits, hares and cottontails. Highly pathogenic viruses such as Rabbit haemorrhagic disease virus 1 (RHDV1) cause a fulminant hepatitis that typically leads to disseminated intravascular coagulation within 24–72 h of infection, killing over 95 % of susceptible animals. Research into the pathophysiological mechanisms that are responsible for this extreme phenotype has been hampered by the lack of a reliable culture system. Here, we report on a new ex vivo model for the cultivation of lagoviruses in cells derived from the European rabbit (Oryctolagus cuniculus) and European brown hare (Lepus europaeus). We show that three different lagoviruses, RHDV1, RHDV2 and RHDVa-K5, replicate in monolayer cultures derived from rabbit hepatobiliary organoids, but not in monolayer cultures derived from cat (Felis catus) or mouse (Mus musculus) organoids. Virus multiplication was demonstrated by (i) an increase in viral RNA levels, (ii) the accumulation of dsRNA viral replication intermediates and (iii) the expression of viral structural and non-structural proteins. The establishment of an organoid culture system for lagoviruses will facilitate studies with considerable implications for the conservation of endangered leporid species in Europe and North America, and the biocontrol of overabundant rabbit populations in Australia and New Zealand.

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Section: Introductionmentioning

confidence: 99%

Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses

Kardia

Fakhri

Pavy

et al. 2023

Journal of General Virology

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show abstract

“…The remaining cell populations comprise hepatic stellate cells, the sinusoidal endothelium, Kupffer cells, specialised hepatic natural killer (NK) cells and itinerant leukocytes [19,20]. Hepatic organoids from several species (humans, mice, dogs, pigs, cats, chickens and trout [21][22][23][24][25][26][27][28][29]) have been generated previously, either from primary biopsy specimens containing hepatic progenitor cells or via the induction of pluripotent stem cells. Here we report the successful cultivation of hepatotropic lagoviruses in non-transformed monolayer cultures derived from rabbit hepatobiliary organoids, while virus replication was not supported in cat or mouse hepatobiliary organoid-derived monolayer cultures.…”

Section: Introductionmentioning

confidence: 99%

Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses

Kardia

Fakhri

Pavy

et al. 2022

Preprint

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Lagoviruses, family Caliciviridae, are some of the most virulent vertebrate viruses known. They infect leporids, i.e., rabbits (Oryctolagus spp.), hares (Lepus spp.) and cottontails (Sylvilagus spp.) and rapidly kill over 95% of susceptible animals. Pathogenic lagoviruses are hepatotropic and induce a fulminant hepatitis that typically leads to disseminated intravascular coagulation within 24-72 hours of infection. However, the pathophysiological mechanisms governing this extreme phenotype and other aspects of the fundamental biology of these viruses are poorly understood due to a lack of cell culture systems. Here, we report on a robust and reliable ex vivo model for the cultivation of hepatotropic lagoviruses. We show that three rabbit haemorrhagic disease virus (RHDV) variants, RHDV1, RHDV2 and RHDVa-K5, replicate in monolayer cultures derived from rabbit hepatobiliary organoids. Viral replication was demonstrated by a (i) increase in viral RNA levels of greater than one log10 over a 23-hour period, (ii) detection of viral structural and non-structural proteins, and (iii) detection of double-stranded RNA viral replication intermediates. Furthermore, we generated hepatobiliary organoids from a feral cat (Felis domesticus), a wild mouse (Mus musculus) and a European brown hare (Lepus europaeus) and showed that monolayer cultures derived from the cat and mouse organoids were not permissive for lagovirus infection, while those derived from the hare organoids only supported replication of RHDV2, recapitulating the species tropism that has been observed with these viruses. Our organoid culture system will facilitate future studies into the molecular biology of lagoviruses, which will have considerable import for the conservation of endangered leporid species in Europe and North America and the biocontrol of overabundant rabbit populations in Australia and New Zealand.

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“…The liver is one of the most important organs in the body, where not only various metabolic processes (e.g., energy, lipid, ferric acid, uric acid metabolism) take place, but it also plays a central role in the detoxification of certain food-derived compounds and noxious substances [ 10 ]. The multiple physiological functions of this organ are mainly ensured by hepatocytes, which constitute more than 80% of the cells of the liver.…”

Section: Introductionmentioning

confidence: 99%

Vitamin E Can Ameliorate Oxidative Damage of Ovine Hepatocytes In Vitro by Regulating Genes Expression Associated with Apoptosis and Pyroptosis, but Not Ferroptosis

et al. 2021

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(1) Background: the current research was conducted to investigate the potential non-antioxidant roles of vitamin E in the protection of hepatocysts from oxidative damage. (2) Methods: primary sheep hepatocytes were cultured and exposed to 200, 400, 600, or 800 μmol/L hydrogen peroxide, while their viability was assessed using a CCK-8 kit. Then, cells were treated with 400 μmol/L hydrogen peroxide following a pretreatment with 50, 100, 200, 400, and 800 μmol/L vitamin E and their intracellular ROS levels were determined by means of the DCF-DA assay. RNA-seq, verified by qRT-PCR, was conducted thereafter: non-treated control (C1); cells treated with 400 μmol/L hydrogen peroxide (C2); and C2 plus a pretreatment with 100 μmol/L vitamin E (T1). (3) Results: the 200–800 μmol/L hydrogen peroxide caused significant cell death, while 50, 100, and 200 μmol/L vitamin E pretreatment significantly improved the survival rate of hepatocytes. ROS content in the cells pretreated with vitamin E was significantly lower than that in the control group and hydrogen-peroxide-treated group, especially in those pretreated with 100 μmol/L vitamin E. The differentially expressed genes (DEGs) concerning cell death involved in apoptosis (RIPK1, TLR7, CASP8, and CASP8AP2), pyroptosis (NLRP3, IL-1β, and IRAK2), and ferroptosis (TFRC and PTGS2). The abundances of IL-1β, IRAK2, NLRP3, CASP8, CASP8AP2, RIPK1, and TLR7 were significantly increased in the C1 group and decreased in T1 group, while TFRC and PTGS2 were increased in T1 group. (4) Conclusions: oxidative stress induced by hydrogen peroxide caused cellular damage and death in sheep hepatocytes. Pretreatment with vitamin E effectively reduced intracellular ROS levels and protected the hepatocytes from cell death by regulating gene expression associated with apoptosis (RIPK1, TLR7, CASP8, and CASP8AP2) and pyroptosis (NLRP3, IL-1β, and IRAK2), but not ferroptosis (TFRC and PTGS2).

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Liver organoids in domestic animals: an expected promise for metabolic studies

Cited by 7 publications

References 64 publications

Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses

Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses

Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses

Vitamin E Can Ameliorate Oxidative Damage of Ovine Hepatocytes In Vitro by Regulating Genes Expression Associated with Apoptosis and Pyroptosis, but Not Ferroptosis

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