دورية أكاديمية
أعرض في EDS

Hepatic cell sheets engineered from human mesenchymal stem cells with a single small molecule compound IC-2 ameliorate acute liver injury in mice.

التفاصيل البيبلوغرافية
العنوان: Hepatic cell sheets engineered from human mesenchymal stem cells with a single small molecule compound IC-2 ameliorate acute liver injury in mice.
المؤلفون: Itaba N; Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan., Noda I; Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan., Oka H; Research Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550, Japan., Kono Y; Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan., Okinaka K; Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan., Yokobata T; Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan., Okazaki S; Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan., Morimoto M; Research Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550, Japan., Shiota G; Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
المصدر: Regenerative therapy [Regen Ther] 2018 Aug 24; Vol. 9, pp. 45-57. Date of Electronic Publication: 2018 Aug 24 (Print Publication: 2018).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: The Japanese Society for Regenerative Medicine. Production and Hosting by Elsevier B.V Country of Publication: Netherlands NLM ID: 101709085 Publication Model: eCollection Cited Medium: Internet ISSN: 2352-3204 (Electronic) Linking ISSN: 23523204 NLM ISO Abbreviation: Regen Ther Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Amsterdam] : The Japanese Society for Regenerative Medicine. Production and Hosting by Elsevier B.V., [2015]-
مستخلص: Introduction: We previously reported that transplantation of hepatic cell sheets from human bone marrow-derived mesenchymal stem cells (BM-MSCs) with hexachlorophene, a Wnt/β-catenin signaling inhibitor, ameliorated acute liver injury. In a further previous report, we identified IC-2, a newly synthesized derivative of the Wnt/β-catenin signaling inhibitor ICG-001, as a potent inducer of hepatic differentiation of BM-MSCs.
Methods: We manufactured hepatic cell sheets by engineering from human BM-MSCs using the single small molecule IC-2. The therapeutic potential of IC-2-induced hepatic cell sheets was assessed by transplantation of IC-2- and hexachlorophene-treated hepatic cell sheets using a mouse model of acute liver injury.
Results: Significant improvement of liver injury was elicited by the IC-2-treated hepatic cell sheets. The expression of complement C3 was enhanced by IC-2, followed by prominent hepatocyte proliferation stimulated through the activation of NF-κB and its downstream molecule STAT-3. Indeed, IC-2 also enhanced the expression of amphiregulin, resulting in the activation of the EGFR pathway and further stimulation of hepatocyte proliferation. As another important therapeutic mechanism, we revealed prominent reduction of oxidative stress mediated through upregulation of the thioredoxin (TRX) system by IC-2-treated hepatic cell sheets. The effects mediated by IC-2-treated sheets were superior compared with those mediated by hexachlorophene-treated sheets.
Conclusion: The single compound IC-2 induced hepatic cell sheets that possess potent regeneration capacity and ameliorate acute liver injury.
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فهرسة مساهمة: Keywords: 8-OHdG, 8-hydroxydeoxyguanosine; A1AT, α1-antitrypsin; ALT, alanine aminotransferase; APOE, apolipoprotein E; AREG, amphiregulin; AST, aspartate aminotransferase; Acute liver failure; BM-MSCs, bone marrow-derived mesenchymal stem cells; C3, complement C3; C4A, complement C4A; C5aR, complement C5a receptor; CBP, CREB-binding protein; CCl4, carbon tetrachloride; CP, ceruloplasmin; ChREBP, Carbohydrate-responsive element-binding protein; ChoREs, carbohydrate response elements; DMSO, dimethyl sulfoxide; EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; GPX, glutathione peroxidase; GR, Glutathione reductase; GRX, glutaredoxin; GSH, glutathione; HB-EGF, heparin binding-epidermal growth factor-like growth factor; HGFR, hepatocyte growth factor receptor; Hepatic cell sheets; IL-1ra, interleukin-1 receptor antagonist; IL-6, interleukin-6; LXR, liver X receptor; Liver regeneration; MDA, malondialdehyde; Mesenchymal stem cells; NF-κB, nuclear factor-kappa B; PCNA, proliferating cell nuclear antigen; PRX, peroxiredoxin; RBP4, retinol binding protein 4; SOD, superoxide dismutase; STAT-3, Signal Tranducer and Activator of Transcription 3; TF, transferrin; TGFα, transforming growth factor alpha; TNFα, tumor necrosis factor alpha; TRX, thioredoxin; TRXR, thioredoxin reductase; Wnt/β-catenin signal inhibitor; hGAPDH, human glyceraldehyde 3-phosphate dehydrogenase; mActb, mouse actin, beta
تواريخ الأحداث: Date Created: 20181208 Latest Revision: 20240403
رمز التحديث: 20240403
مُعرف محوري في PubMed: PMC6222293
DOI: 10.1016/j.reth.2018.07.001
PMID: 30525075
قاعدة البيانات: MEDLINE
الوصف
تدمد:2352-3204
DOI:10.1016/j.reth.2018.07.001