{
    "abstract": "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.\nThis 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.\nSecreted 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\u00a0fg/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.\nThe 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.",
    "authors": [
        {
            "affiliation": "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.",
            "firstname": "Kenji",
            "initials": "K",
            "lastname": "Fukushima"
        },
        {
            "affiliation": "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.",
            "firstname": "Noriko",
            "initials": "N",
            "lastname": "Itaba"
        },
        {
            "affiliation": "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.",
            "firstname": "Yohei",
            "initials": "Y",
            "lastname": "Kono"
        },
        {
            "affiliation": "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.",
            "firstname": "Shizuma",
            "initials": "S",
            "lastname": "Okazaki"
        },
        {
            "affiliation": "Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University, Yonago, 683-8504, Japan.",
            "firstname": "Shinpei",
            "initials": "S",
            "lastname": "Enokida"
        },
        {
            "affiliation": "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.",
            "firstname": "Naomi",
            "initials": "N",
            "lastname": "Kuranobu"
        },
        {
            "affiliation": "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.",
            "firstname": "Jun",
            "initials": "J",
            "lastname": "Murakami"
        },
        {
            "affiliation": "Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University, Yonago, 683-8504, Japan.",
            "firstname": "Makoto",
            "initials": "M",
            "lastname": "Enokida"
        },
        {
            "affiliation": "Division of Orthopedic Surgery, Department of Sensory and Motor Organs, School of Medicine, Faculty of Medicine, Tottori University, Yonago, 683-8504, Japan.",
            "firstname": "Hideki",
            "initials": "H",
            "lastname": "Nagashima"
        },
        {
            "affiliation": "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.\nAsahigawaso Rehabilitation & Medical Center, Okayama, 703-8555, Japan.",
            "firstname": "Susumu",
            "initials": "S",
            "lastname": "Kanzaki"
        },
        {
            "affiliation": "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.",
            "firstname": "Noriyuki",
            "initials": "N",
            "lastname": "Namba"
        },
        {
            "affiliation": "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.",
            "firstname": "Goshi",
            "initials": "G",
            "lastname": "Shiota"
        }
    ],
    "conclusions": "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.",
    "copyrights": "\u00a9 2021 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.",
    "doi": "10.1016/j.reth.2021.08.004\n10.1371/journal.pbio.3000410",
    "journal": "Regenerative therapy",
    "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/\u03b2-catenin signal inhibitor",
        "chronic liver injury",
        "hBM-MNCs, human bone marrow mononuclear cells",
        "iPS cells, induced pluripotent stem cells",
        "\u03b1SMA, \u03b1-smooth muscle actin"
    ],
    "methods": null,
    "publication_date": "2021-09-11",
    "pubmed_id": "34504910\n28487545\n27557303\n29156048\n25920084\n25626988\n25242656\n26255044\n31698008\n30928109\n22378017\n28970712\n20583084\n18455168\n28906582\n10848804\n10102814\n17651977\n26073566\n24855521\n17909019\n20603892\n28287644\n28974553\n27339398\n22546280\n17627621\n17884977\n31245457\n30525075\n31048740\n17572687\n31768801\n32663219\n23554877\n28406755\n23903700\n24353357\n2868469\n11682030\n26553591\n25794647\n12459476\n8663332\n28322443\n15629516\n10404011\n22395436\n15820210\n18716372\n16256786\n26021843\n32070429",
    "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\u00a0fg/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.",
    "title": "Secreted matrix metalloproteinase-14 is a predictor for antifibrotic effect of IC-2-engineered mesenchymal stem cell sheets on liver fibrosis in mice.",
    "xml": "<Element 'PubmedArticle' at 0x788505c0ea70>"
}