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  • 1
    Online Resource
    Online Resource
    Pancreas Preservation in Modified Histidine-lactobionate Solution Is Superior to That in University of Wisconsin Solution for Porcine Islet Isolation
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Transplantation Vol. 106, No. 9 ( 2022-09), p. 1770-1776
    Details
    In: Transplantation, Ovid Technologies (Wolters Kluwer Health), Vol. 106, No. 9 ( 2022-09), p. 1770-1776
    Abstract: We previously reported that modified extracellular-type trehalose-containing Kyoto (MK) solution, which contains a trypsin inhibitor (ulinastatin), significantly improved the islet yield compared with University of Wisconsin (UW) preservation, which is the gold standard for organ preservation for islet isolation. In this study, we evaluated the efficiency of a modified histidine-lactobionate (MHL) solution in addition to UW or MK solution. The MHL solution has a high sodium-low potassium composition with low viscosity compared with the UW solution. Moreover, similar to MK solution, MHL solution also contains ulinastatin. Methods. Porcine pancreata were preserved in UW, MK, or MHL solution, followed by islet isolation. An optimized number (1500 IE) of isolated islets from each group were then transplanted into streptozotocin-induced diabetic mice. Results. The islet yield before and after purification was significantly higher in the MHL group than in the UW group. On the contrary, the islet yield before and after purification was not significantly different between the MHL and MK groups. Preserving the porcine pancreata in MHL solution improved the outcome of islet transplantation in streptozotocin-induced diabetic mice compared with that in UW solution. Conclusions. Pancreas preservation with MHL solution preserves islet function better than UW solution. The effect of MHL solution is similar to that of MK solution, suggesting that MHL solution can be used as an alternative to MK solution for pancreatic islet transplantation.
    Type of Medium: Online Resource
    ISSN: 0041-1337
    URL: Article
    DOI: 10.1097/TP.0000000000003636
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2035395-9
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  • 2
    Online Resource
    Online Resource
    Cryopreservation of Adipose-Derived Mesenchymal Stem Cells
    SAGE Publications ; 2015
    In:  Cell Medicine Vol. 8, No. 1-2 ( 2015-08), p. 3-7
    Details
    In: Cell Medicine, SAGE Publications, Vol. 8, No. 1-2 ( 2015-08), p. 3-7
    Abstract: Mesenchymal stem cells (MSCs) have the potential to differentiate into cells of mesodermal origin such as osteoblasts, adipocytes, myocytes, and chondrocytes. They possess an immunosuppressive effect, which makes them a viable cell population for the cell-based therapy of treatment-resistant immune diseases. Adipose-derived mesenchymal stem cells (ASCs) have been demonstrated to have the ability to acquire the properties of subcutaneous adipose tissue particularly easily, and cryopreservation is currently performed as a routine method for preserving ASCs to safely acquire large numbers of cells. However, many studies have reported that cellular activity after freezing and thawing may be affected by the solutions used for cryopreservation. Dimethyl sulfoxide (DMSO) is commonly used as a cryopreservation medium as it diffuses into the cell through the plasma membrane and protects the cells from the damage caused by freezing. As substitutes for DMSO or animal-derived serum, cell banker series, polyvinylpyrrolidone (PVP), sericin and maltose, and methyl cellulose (MC) have been investigated for their clinical applications. It is critical to develop a reliable cell cryopreservation protocol for regenerative medicine using MSCs.
    Type of Medium: Online Resource
    ISSN: 2155-1790 , 2155-1790
    URL: Article
    DOI: 10.3727/215517915X689100
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2634804-4
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  • 3
    Online Resource
    Online Resource
    The Evaluation of Islet Purification Methods That Use Large Bottles to Create a Continuous Density Gradient
    SAGE Publications ; 2017
    In:  Cell Medicine Vol. 9, No. 1-2 ( 2017-01), p. 45-51
    Details
    In: Cell Medicine, SAGE Publications, Vol. 9, No. 1-2 ( 2017-01), p. 45-51
    Abstract: Islet purification is one of the most important steps of islet isolation for pancreatic islet transplantation. The most common method of islet purification is density gradient centrifugation using a COBE 2991 cell processor. However, this method can damage islets mechanically through its high shearing force. We recently reported that a new purification method using large plastic bottles effectively achieves a high yield of islets from the porcine pancreas. In the present study, we evaluated the methods of making a continuous density gradient. The gradient was produced with a gradient maker and two types of candy cane-shaped stainless steel pipes. One method was to use a “bent-tipped” stainless steel pipe and to load from a high-density solution to a low-density solution, uploading the stainless steel pipe. The other method was to use a regular stainless steel pipe and to load from a low-density solution to a high-density solution, leaving the stainless steel pipe in place. There were no significant differences between the two solutions in terms of the islet yield, rate of viability or purity, score, or the stimulation index after purification. Furthermore, there were no differences in the attainability or suitability of posttransplantation normoglycemia. Our study shows the equivalency of these two methods of islet purification.
    Type of Medium: Online Resource
    ISSN: 2155-1790 , 2155-1790
    URL: Article
    DOI: 10.3727/215517916X693131
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
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  • 4
    Online Resource
    Online Resource
    Role of Egr1 on Pancreatic Endoderm Differentiation
    SAGE Publications ; 2018
    In:  Cell Medicine Vol. 10 ( 2018-01-01), p. 215517901773317-
    Details
    In: Cell Medicine, SAGE Publications, Vol. 10 ( 2018-01-01), p. 215517901773317-
    Abstract: The low efficiency of in vitro differentiation of human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (iPSCs) into insulin-producing cells is a crucial hurdle for the clinical implementation of human pluripotent stem cells (PSCs). Our previous investigation into the key factors for the differentiation of PSCs into insulin-producing cells suggested that the expression of GATA binding protein 6 (GATA6) and Gremlin 1 (GREM1) and inhibition of early growth response protein 1 (Egr1) may be important factors. In this study, we investigated the role of Egr1 in pancreas development. The transfection of small interfering RNA (siRNA) of Egr1 in the early phase induced the differentiation of iPSCs derived from fibroblasts (FiPSCs) into pancreatic endoderm and insulin-producing cells. In contrast, the downregulation of Egr1 in the late phase suppressed the differentiation of FiPSCs into pancreatic endoderm and insulin-producing cells. In addition, the overexpression of Egr1 suppressed the differentiation of iPSCs derived from pancreatic cells into pancreatic endoderm and insulin-producing cells. These data suggest that the downregulation of Egr1 in the early phase can efficiently induce the differentiation of iPSCs into insulin-producing cells.
    Type of Medium: Online Resource
    ISSN: 2155-1790 , 2155-1790
    URL: Article
    DOI: 10.1177/2155179017733177
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 2634804-4
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  • 5
    Online Resource
    Online Resource
    The Development of Cancer through the Transient Overexpression of Reprogramming Factors
    SAGE Publications ; 2018
    In:  Cell Medicine Vol. 10 ( 2018-01-01), p. 215517901773317-
    Details
    In: Cell Medicine, SAGE Publications, Vol. 10 ( 2018-01-01), p. 215517901773317-
    Abstract: Although induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem cells, several issues related to the use of iPS cells in clinical applications remain unresolved, including the issue of teratoma formation. We previously reported that the induction of induced tissue-specific stem (iTS) cells from the pancreas (iTS-P) or liver (iTS-L) by the transient overexpression of reprogramming factors, combined with tissue-specific selection and the generation of iTS cells, could have important implications for the clinical application of stem cells. At the same time, we also generated “induced fibroblast-like (iF) cells” that were capable of self-renewal, which had a similar morphology to fibroblast cells. In this study, we evaluated iF cells. iF cells are unlikely to show adipogenic/osteogenic differentiation. Moreover, iF cells have the ability to form tumors and behave similarly to pancreatic cancer cells. The technology used in the generation of iPS/iTS cells is also associated with the risk of generating cancer-like cells.
    Type of Medium: Online Resource
    ISSN: 2155-1790 , 2155-1790
    URL: Article
    DOI: 10.1177/2155179017733172
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 2634804-4
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  • 6
    Online Resource
    Online Resource
    Evaluation of Islet Purification Methods for Making a Continuous Density Gradient and Loading Tissue
    SAGE Publications ; 2018
    In:  Cell Medicine Vol. 10 ( 2018-01-01), p. 215517901773309-
    Details
    In: Cell Medicine, SAGE Publications, Vol. 10 ( 2018-01-01), p. 215517901773309-
    Abstract: Islet purification is one of the most important steps of islet isolation for pancreatic islet transplantation. We previously reported that a purification method using large plastic bottles effectively achieved a high yield of islets from porcine pancreas. In this study, we evaluated the methods for making a continuous density gradient and loading tissue. One method involved loading digested tissue on top of a continuous density gradient (top loading). The other method involved mixing digested tissue with low-density solution and then making a continuous gradient (mixed loading). There were no significant differences between the 2 purification methods in terms of the islet yield, rate of viability or purity, score, or in the stimulation index after purification. Furthermore, there were no marked differences in the attainability or suitability of posttransplantation normoglycemia. Our study shows the equivalency of these 2 methods of islet purification.
    Type of Medium: Online Resource
    ISSN: 2155-1790 , 2155-1790
    URL: Article
    DOI: 10.1177/2155179017733090
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 2634804-4
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  • 7
    Online Resource
    Online Resource
    Cytoprotective Effect of Pteryxin on Insulinoma MIN6 Cells Due to Antioxidant Enzymes Expression via Nrf2/ARE Activation
    MDPI AG ; 2023
    In:  Antioxidants Vol. 12, No. 3 ( 2023-03-10), p. 693-
    Details
    In: Antioxidants, MDPI AG, Vol. 12, No. 3 ( 2023-03-10), p. 693-
    Abstract: The low-level antioxidant activity of pancreatic islets causes type 1 diabetes due to oxidative stress, which is also the cause of failure in the pancreatic islets’ isolation and cell transplantation. In our previous study, pteryxin was found to be a natural product as a nuclear factor-erythroid-2-related factor (Nrf2) activator. This study focused on elucidation that the potentiality of pteryxin can activate the antioxidant enzymes, even under oxidative stress, by hydrogen peroxide (H2O2). Pteryxin treated with mouse insulinoma MIN6 cells was enhanced the antioxidant gene expressions in the ARE (antioxidant response element) region for HO-1 (Heme Oxygenase-1), GCLC (Glutamate-cysteine ligase catalytic subunit), SOD1 (Super Oxide dismutase1), and Trxr1 (Thioredoxin reductase1), and those enzymes were also expressed during the nuclei transference of cytoplasmic Nrf2. In fact, the cells exposed to H2O2 concentrations of a half-cell lethal in the presence of pteryxin were then induced main antioxidant enzymes, HO-1, GCLC, and Trxr1 in the ARE region. The increased glutathione (GSH) levels associated with the GCLC expression also suggested to be cytoprotective against oxidative stress by activating the redox-metabolizing enzymes involving their increased antioxidant activity in the cells. In addition, Akt is a modulator for Nrf2, which may be responsible for the Nrf2 activation. These results allowed us to consider whether pteryxin or its synthesized congeners, an Nrf2 activator, is a potential preservative agent against islet isolation during cell transplantation.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox12030693
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 8
    Online Resource
    Online Resource
    Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors
    Elsevier BV ; 2019
    In:  Molecular Therapy - Methods & Clinical Development Vol. 13 ( 2019-06), p. 243-252
    Details
    In: Molecular Therapy - Methods & Clinical Development, Elsevier BV, Vol. 13 ( 2019-06), p. 243-252
    Type of Medium: Online Resource
    ISSN: 2329-0501
    URL: Article
    DOI: 10.1016/j.omtm.2019.01.011
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 2863173-0
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  • 9
    Online Resource
    Online Resource
    In vivo evaluation of GG2–GG1/A2 element activity in the insulin promoter region using the CRISPR–Cas9 system
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-10-13)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-10-13)
    Abstract: The insulin promoter is regulated by ubiquitous as well as pancreatic β-cell-specific transcription factors. In the insulin promoter, GG2–GG1/A2–C1 (bases − 149 to − 116 in the human insulin promoter) play important roles in regulating β-cell-specific expression of the insulin gene. However, these events were identified through in vitro studies, and we are unaware of comparable in vivo studies. In this study, we evaluated the activity of GG2–GG1/A2 elements in the insulin promoter region in vivo. We generated homozygous mice with mutations in the GG2–GG1/A2 elements in each of the Ins1 and Ins2 promoters by CRISPR–Cas9 technology. The mice with homozygous mutations in the GG2–GG1/A2 elements in both Ins1 and Ins2 were diabetic. These data suggest that the GG2–GG1/A2 element in mice is important for Ins transcription in vivo.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-021-99808-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 10
    Online Resource
    Online Resource
    Comparison of Tissue Loading Before and After the Creation of a Continuous Density Gradient in Porcine Islet Purification
    SAGE Publications ; 2018
    In:  Cell Medicine Vol. 10 ( 2018-01-01), p. 215517901878134-
    Details
    In: Cell Medicine, SAGE Publications, Vol. 10 ( 2018-01-01), p. 215517901878134-
    Abstract: The purification step is one of the most important and difficult procedures in islet isolation for pancreatic islet transplantation. We previously reported that a purification method using large plastic bottles effectively achieved a high yield of islets from the porcine pancreas. In this study, we evaluated the impact of the timing of tissue loading on porcine islet purification using large plastic bottles. One method involved loading digested tissue after creating a continuous density gradient (tissue after gradient [TAG]). The other method involved loading digested tissue before creating a continuous density gradient (tissue before gradient [TBG] ). There were no significant differences between TAG and TBG in terms of the islet yield, rates of viability and purity, score, and in the stimulation index after purification. Furthermore, there were no marked differences in the attainability or suitability of post-transplantation normoglycemia. Our study shows the equivalency of these two methods of islet purification.
    Type of Medium: Online Resource
    ISSN: 2155-1790 , 2155-1790
    URL: Article
    DOI: 10.1177/2155179018781343
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 2634804-4
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