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Secreted matrix metalloproteinase-14 is a predictor for antifibrotic effect of IC-2-engineered mesenchymal stem cell sheets on liver fibrosis in mice.

التفاصيل البيبلوغرافية
العنوان: Secreted matrix metalloproteinase-14 is a predictor for antifibrotic effect of IC-2-engineered mesenchymal stem cell sheets on liver fibrosis in mice.
المؤلفون: Fukushima K; Division of Pediatrics and Perinatology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8504, Japan., Itaba N; Division of Medical Genetics and Regenerative Medicine, Department of Genomic Medicine and Regenerative Therapy, School of Medicine, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan., Kono Y; Division of Medical Genetics and Regenerative Medicine, Department of Genomic Medicine and Regenerative Therapy, School of Medicine, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan., Okazaki S; Division of Medical Genetics and Regenerative Medicine, Department of Genomic Medicine and Regenerative Therapy, School of Medicine, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan., Enokida S; Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University, Yonago, 683-8504, Japan., Kuranobu N; Division of Pediatrics and Perinatology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8504, Japan., Murakami J; Division of Pediatrics and Perinatology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8504, Japan., Enokida M; Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University, Yonago, 683-8504, Japan., Nagashima H; Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University, Yonago, 683-8504, Japan., Kanzaki S; Division of Pediatrics and Perinatology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8504, Japan.; Asahigawaso Rehabilitation & Medical Center, Okayama, 703-8555, Japan., Namba N; Division of Pediatrics and Perinatology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8504, Japan., Shiota G; Division of Medical Genetics and Regenerative Medicine, Department of Genomic Medicine and Regenerative Therapy, School of Medicine, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan.
المصدر: Regenerative therapy [Regen Ther] 2021 Aug 26; Vol. 18, pp. 292-301. Date of Electronic Publication: 2021 Aug 26 (Print Publication: 2021).
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: Transplantation of IC-2-engineered bone marrow-derived mesenchymal stem cell (BM-MSC) sheets (IC-2 sheets) was previously reported to potentially reduce liver fibrosis.
Methods: This study prepared IC-2-engineered cell sheets from multiple lots of BM-MSCs and examined the therapeutic effects of these cell sheets on liver fibrosis induced by carbon tetrachloride in mice. The predictive factors for antifibrotic effect on liver fibrosis were tried to identify in advance.
Results: Secreted matrix metalloproteinase (MMP)-14 was found to be a useful predictive factor to reduce liver fibrosis. Moreover, the cutoff index of MMP-14 for 30% reduction of liver fibrosis was 0.918 fg/cell, judging from univariate analysis and receiver operating curve analysis. In addition, MMP-13 activity and thioredoxin contents in IC-2 sheets were also inversely correlated with hepatic hydroxyproline contents. Finally, IC-2 was also found to promote MMP-14 secretion from BM-MSCs of elderly patients. Surprisingly, the values of secreted MMP-14 from BM-MSCs of elderly patients were much higher than those of young persons.
Conclusion: The results of this study suggest that the IC-2 sheets would be applicable to clinical use in autologous transplantation for patients with cirrhosis regardless of the patient's age.
Competing Interests: G.S. holds more than 5% of the total shares of KanonCure Inc. and receives compensation as a member of KanonCure Inc. The other authors have no competing interests to declare. Tottori university and KanonCure Inc. have the patents for IC-2 sheets (patent registration numbers, US 9,555,061, DE602012040872.3, ES2698365, FR2698365, GB269835, and IT502018000006592), and patent applications (patent application numbers TW107129167, US16/641,874, CN201880054224.7, EP18851336.0, PCT/JP2019/021603, US16/972,285, and EP198156721).
(© 2021 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)
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فهرسة مساهمة: Keywords: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BM-MSCs, bone marrow-derived mesenchymal stem cells; C3, complement C3; CCl4, carbon tetrachloride; DMSO, dimethyl sulfoxide; EDTA, ethylenediamine tetra-acetic acid; FACS, Fluorescence-activated cell sorter; FALD, fontan-associated liver disease; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; HCC, hepatic cellular carcinoma; HLA, human leukocyte antigen; HSCs, hepatic stellate cells; Hepatic cell sheets; IgG, immunoglobulin G; LC, liver cirrhosis; MMP-14, matrix metalloproteinase; MSCs, mesenchymal stem cells; Matrix metalloproteinase-14; Mesenchymal stem cells; Wnt/β-catenin signal inhibitor; chronic liver injury; hBM-MNCs, human bone marrow mononuclear cells; iPS cells, induced pluripotent stem cells; αSMA, α-smooth muscle actin
تواريخ الأحداث: Date Created: 20210910 Latest Revision: 20220426
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8399086
DOI: 10.1016/j.reth.2021.08.004
PMID: 34504910
قاعدة البيانات: MEDLINE
الوصف
تدمد:2352-3204
DOI:10.1016/j.reth.2021.08.004