The Regenerative Effect of Portal Vein Injection of Liver Organoids by Retrorsine/Partial Hepatectomy in Rats

Tsuchida, Takayasu; Murata, Soichiro; Matsuki, Koichiro; Mori, Akira; Matsuo, Megumi; Mikami, Satoshi; Okamoto, Satoshi; Ueno, Yasuharu; Tadokoro, Tomomi; Zheng, Yun‐Wen; Taniguchi, Hideki

doi:10.3390/ijms21010178

Cited by 26 publications

(24 citation statements)

References 30 publications

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“…Accordingly, three GO terms including “response to sucrose” (GO:0009744), “response to glucose” (GO:0009749) and “response to fructose” (GO:0009750) were enriched among the DEGs, suggesting the accumulation of these sugars. Raffinose family oligosaccharides (RFOs) are α-1, 6-galactosyl extensions of sucrose [ 77 ] and have been reported to accumulate significantly under low temperature stress [ 78 – 80 ]. Stachyose synthase, galactinol synthase and galactinol-sucrose galactosyltransferase are important for the biosynthesis of RFOs.…”

Section: Discussionmentioning

confidence: 99%

Responses of Manila Grass (Zoysia matrella) to chilling stress: From transcriptomics to physiology

et al. 2020

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Manila grass (Zoysia matrella), a warm-season turfgrass, usually wilts and browns by late autumn because of low temperature. To elucidate the molecular mechanisms regarding Manila grass responses to cold stress, we performed transcriptome sequencing of leaves exposed to 4˚C for 0 (CK), 2h (2h_CT) and 72h (72h_CT) by Illumina technology. Approximately 250 million paired-end reads were obtained and de novo assembled into 82,605 unigenes. A total of 34,879 unigenes were annotated by comparing their sequence to public protein databases. At the 2h-and 72h-cold time points, 324 and 5,851 differentially expressed genes (DEGs) were identified, respectively. Gene ontology (GO) and metabolism pathway (KEGG) enrichment analyses of DEGs indicated that auxin, gibberellins, ethylene and calcium took part in the cold signal transduction in the early period. And in the late cold period, electron transport activities, photosynthetic machinery and activity, carbohydrate and nitrogen metabolism, redox equilibrium and hormone metabolism were disturbed. Low temperature stress triggered high light, drought and oxidative stress. At the physiological level, cold stress induced a decrease in water content, an increase in levels of total soluble sugar, free proline and MDA, and changes in bioactive gibberellins levels, which supported the changes in gene expression. The results provided a large set of sequence data of Manila grass as well as molecular mechanisms of the grass in response to cold stress. This information will be helpful for future study of molecular breeding and turf management.

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Section: Discussionmentioning

confidence: 99%

Responses of Manila Grass (Zoysia matrella) to chilling stress: From transcriptomics to physiology

et al. 2020

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“…The hiPSCs (Ff-I01s04) were maintained on Laminin 511 E8 fragment-coated (iMatrix-511, kindly provided by Nippi, Incorporated, Tokyo, Japan) dishes in StemFit AK02N (Ajinomoto, Tokyo, Japan). The hiPSCs were differentiated into Hepatic endoderm (HE), endothelial (EC), and mesenchymal cells (MC), as described previously [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

“…The seeded cell number for HE was 2.5 × 10 6 cells, for EC, 1 × 10 6 cells, and, for MC, 1 × 10 6 cells per well. The culture medium used was the same as reported previously [ 25 ]. Y-27632 (FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan) was added on day one.…”

Section: Methodsmentioning

confidence: 99%

Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models

Mori

Murata

Tashiro

et al. 2021

Cells

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Humanized mouse models have contributed significantly to human immunology research. In transplant immunity, human immune cell responses to donor grafts have not been reproduced in a humanized animal model. To elicit human T-cell immune responses, we generated immune-compromised nonobese diabetic/Shi-scid, IL-2RγKO Jic (NOG) with a homozygous expression of human leukocyte antigen (HLA) class I heavy chain (NOG-HLA-A2Tg) mice. After the transplantation of HLA-A2 human hematopoietic stem cells into NOG-HLA-A2Tg, we succeeded in achieving alloimmune responses after the HLA-mismatched human-induced pluripotent stem cell (hiPSC)-derived liver-like tissue transplantation. This immune response was inhibited by administering tacrolimus. In this model, we reproduced allograft rejection after the human iPSC-derived liver-like tissue transplantation. Human tissue transplantation on the humanized mouse liver surface is a good model that can predict T-cell-mediated cellular rejection that may occur when organ transplantation is performed.

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“…Fetal cell donors were obtained by the Caesarian section of pregnant hKO pigs at 30 days of gestation. Unfractionated fetal liver cells were isolated as previously described 9 . Harvested fetal liver cells were suspended in 10 ml of William’s E Medium (Thermo Fisher Scientific, Waltham, MA, USA) supplemented with the following: 10% fetal bovine serum (MP Biomedicals, LLC, Irvine, CA, USA), 2 mM l -glutamine (Thermo Fisher Scientific), 1% penicillin/streptomycin (Thermo Fisher Scientific), 10 mM nicotinamide (Sigma-Aldrich, St. Louis, MO, USA), 50 μM 2-ME (β-ME; Sigma-Aldrich), 260 mM l -ascorbic acid 2-phosphate sesquimagnesium salt hydrate (Sigma-Aldrich), 5 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (Dojindo Laboratories, Kumamoto, Japan), and 1 μg/ml human recombinant insulin expressed in yeast (FUJIFILM Wako Pure Chemical Corporation).…”

Section: Methodsmentioning

confidence: 99%

“…We recently reported that human iPSC-derived liver organoid transplantation via the portal vein does not allow translocation of organoids outside the liver, whereas, in one experiment, a single-cell component of the liver organoid translocated to the lung in an adult mouse. The diameter of a human iPSC-derived organoid is 130 µm 9 .…”

Section: Introductionmentioning

confidence: 99%

Investigation of Clinical Safety of Human iPS Cell-Derived Liver Organoid Transplantation to Infantile Patients in Porcine Model

et al. 2020

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Transplantation of liver organoids has been investigated as a treatment alternative to liver transplantation for chronic liver disease. Transportal approach can be considered as a method of delivering organoids to the liver. It is important to set the allowable organoid amount and verify translocation by intraportal transplantation. We first examined the transplantation tolerance and translocation of porcine fetal liver-derived allogeneic organoids using piglets. Fetal liver-derived organoids generated from the Kusabira Orange-transduced pig were transplanted to the 10-day-old piglet liver through the left branch of the portal vein. All recipients survived without any observable adverse events. In contrast, both local and main portal pressures increased transiently during transplantation. In necropsy samples, Kusabira Orange-positive donor cells were detected primarily in the target lobe of the liver and partly in other areas, including the lungs and brain. As we confirmed the transplantation allowance by porcine fetal liver-derived organoids, we performed intraportal transplantation of human-induced pluripotent stem cell (iPSC)-derived liver organoid, which we plan to use in clinical trials, and portal pressure and translocation were investigated. Human iPSC-derived liver organoids were transplanted into the same 10-day-old piglet. Portal hypertension and translocation of human iPSC-derived liver organoids to the lungs were observed in one of two transplanted animals. Translocation occurred in the piglet in which patent ductus venosus (PDV) was observed. Therefore, a 28-day-old piglet capable of surgically ligating PDV was used, and after the PDV was ligated, human iPSC-derived liver organoids with the amount of which is scheduled in clinical trials were transplanted. This procedure inhibited the translocation of human iPSC-derived liver organoids to extrahepatic sites without no portal hypertension. In conclusion, human iPSC-derived liver organoids can be safely transplanted through the portal vein. Ligation of the ductus venosus prior to transplantation was effective in inhibiting extrahepatic translocation in newborns and infants.

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The Regenerative Effect of Portal Vein Injection of Liver Organoids by Retrorsine/Partial Hepatectomy in Rats

Cited by 26 publications

References 30 publications

Responses of Manila Grass (Zoysia matrella) to chilling stress: From transcriptomics to physiology

Responses of Manila Grass (Zoysia matrella) to chilling stress: From transcriptomics to physiology

Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models

Investigation of Clinical Safety of Human iPS Cell-Derived Liver Organoid Transplantation to Infantile Patients in Porcine Model

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