Drug Delivery System
Online ISSN : 1881-2732
Print ISSN : 0913-5006
ISSN-L : 0913-5006
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Volume 35, Issue 4
Application of iPS cells of DDS
Displaying 1-12 of 12 articles from this issue
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[Feature articles] “Application of iPS cells of DDS” Editor:Hideki Taniguchi
  • [FOREWORD]Application of iPS cells of DDS
    Hideki Taniguchi
    2020 Volume 35 Issue 4 Pages 275
    Published: September 25, 2020
    Released on J-STAGE: December 26, 2020
    DOIhttps://doi.org/10.2745/dds.35.275
    JOURNAL FREE ACCESS
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  • [OPINION]Neo Drug Delivery System” by Organoid
    Tomoyuki Yamaguchi
    2020 Volume 35 Issue 4 Pages 276
    Published: September 25, 2020
    Released on J-STAGE: December 26, 2020
    DOIhttps://doi.org/10.2745/dds.35.276
    JOURNAL FREE ACCESS
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  • Development of enzyme replacement therapy using liver organoids derived from human iPS cells
    Yasuharu Ueno, Hideki Taniguchi
    2020 Volume 35 Issue 4 Pages 278-284
    Published: September 25, 2020
    Released on J-STAGE: December 26, 2020
    DOIhttps://doi.org/10.2745/dds.35.278
    JOURNAL FREE ACCESS
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    Ammonia is a toxic substance that results from the metabolism of proteins. The liver is responsible for the metabolism of ammonia, which can be harmful to the body. Within hepatocytes, toxic ammonia is converted into urea, by the action of the multiple enzymes involved in the urea cycle, and subsequently excreted in urine. However, patients with gene mutations in their urea cycle enzymes have abnormal ammonia metabolism, which leads to hyperammonemia. While liver transplantation is the best option for treating urea cycle disorders, it is limited by donor availability. Following the advances in stem cell technology, a new method has been developed to create a three-dimensional tissue (an organoid) with functional liver characteristics. Because this organoid is generated from human iPS cells, using it avoids donor availability issues. In this paper, we outline the research progress on urea cycle disorders and discuss the possibility of treating them using organoids derived from human iPS cells.
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  • Hormone replacement therapy using human iPS cell-derived pituitary organoids
    Shiori Taga, Hidetaka Suga, Toru Kimura, Hiroshi Arima
    2020 Volume 35 Issue 4 Pages 285-292
    Published: September 25, 2020
    Released on J-STAGE: December 26, 2020
    DOIhttps://doi.org/10.2745/dds.35.285
    JOURNAL FREE ACCESS
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    The pituitary is a major endocrine center for systemic hormones, secreting various hormones such as ACTH and GH that are critical for survival, homeostasis and growth. Therefore, once it becomes dysfunctional, it will cause a wide range of serious symptoms. The current treatment for hypopituitarism is hormone replacement therapy, but not a curative treatment, so it is hoped regenerative medicine will become a superior treatment. We have succeeded in generating a functional anterior pituitary from mouse and human embryonic stem cells, and showed its therapeutic efficacy for pituitary disorders. In this article, we discuss the current research progression in and future perspectives of pituitary regenerative medicine.
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  • Insulin replacement therapy using human iPS-derived islet-like spheroid
    Hitoshi Okochi, Shigeharu Yabe, Atsushi Miyajima
    2020 Volume 35 Issue 4 Pages 293-300
    Published: September 25, 2020
    Released on J-STAGE: December 26, 2020
    DOIhttps://doi.org/10.2745/dds.35.293
    JOURNAL FREE ACCESS
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    Diabetes mellitus is caused by the shortage of insulin as well as overproduction of glucagon which elevates blood glucose levels. Islet transplantation is currently applied to the severe type I diabetes mellitus patients who suffer from frequent hypoglycemic attack. However, one of the problems of islet transplantation is donor shortage. To solve this problem, we paid attention to the human iPS cells and we developed efficient generation of human islet-like cells from them recently. Another problem of islet transplantation is that recipients have to take immunosuppressants for a long time to avoid rejection reaction. If we encapsulate islets properly, transplanted islets can escape the attack of immune cells. We confirmed that human iPS-derived islet-like spheroids encapsulated into alginate fiber ameliorated hyperglycemia in diabetic model mice when they were transplanted intraperitoneously. For the clinical application, we need further improvement of devices.
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  • Cell transplantation therapy using induced pluripotent stem cell-derived dopaminergic progenitors for Parkinson's disease
    Daisuke Doi, Jun Takahashi
    2020 Volume 35 Issue 4 Pages 301-308
    Published: September 25, 2020
    Released on J-STAGE: December 26, 2020
    DOIhttps://doi.org/10.2745/dds.35.4
    JOURNAL FREE ACCESS
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    Cell transplantation therapy for Parkinson's disease has been shown to be effective in some cases in clinical trials of fetal cell transplantation. Based on these results, research has been conducted by using pluripotent stem cells, such as embryonic stem（ES） cells and induced pluripotent stem（iPS） cells, as a cell supply source. Clinical trials of cell transplantation therapy using pluripotent stem cells have recently been initiated around the world, and in Japan, a Physician-led clinical trial using iPS cells were initiated in 2018. In this article, we discuss the history of cell transplantation therapy for Parkinson's disease and details of development of cell transplantation therapy using pluripotent stem cells, including pre-clinical studies for the clinical trial. The indications, methods, and risks in the clinical trials are also outlined.
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  • Potential of human iPS cell-derived intestinal epithelial cells as a tool for pharmacokinetic assessment
    Tomoki Yamashita, Jumpei Yokota, Tatsuya Inui, Hiroyuki Mizuguchi
    2020 Volume 35 Issue 4 Pages 309-318
    Published: September 25, 2020
    Released on J-STAGE: December 26, 2020
    DOIhttps://doi.org/10.2745/dds.35.309
    JOURNAL FREE ACCESS
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    The efficient development of safe, orally administered drugs requires accurate prediction of pharmacokinetics in the patient’s intestine at the preclinical stage. However, the current in vitro intestinal pharmacokinetic assay systems have several drawbacks, including species differences and low（or no） expression of drug-metabolizing enzymes and transporters. Therefore, it is expected that intestinal epithelial cells generated from human iPS cells（human iPS cell-derived intestinal epithelial cells） will be used to evaluate the pharmacokinetics of drugs in the human intestinal tract. There are two main methods for generating human iPS cell-derived intestinal epithelial cells: those involving three-dimensional culture（intestinal organoids） and those involving consistent two-dimensional culture. In this review, we discuss the pharmacokinetic applications of human iPS cell-derived intestinal epithelial cells generated by each method.
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  • Generation of cells to support drug discovery research using human iPS cells
    Takahiro Iwao, Tadahiro Hashita, Tamihide Matsunaga
    2020 Volume 35 Issue 4 Pages 319-330
    Published: September 25, 2020
    Released on J-STAGE: December 26, 2020
    DOIhttps://doi.org/10.2745/dds.35.entryPoint
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    Using primary human intestinal epithelial cells and brain microvascular endothelial cells （BMECs） for the evaluation of drug membrane permeability would be desirable, but they have poor viability and other characteristics such as short life span that limit their application. In addition, it is very difficult to obtain primary human small intestinal epithelial cells and BMECs for drug discovery research such as pharmacokinetic studies and safety tests of drug candidates. To accurately predict the pharmacokinetics of the human small intestine and blood–brain barrier （BBB）, the development of human induced pluripotent stem （iPS） cell–derived intestinal epithelial cells and brain microvascular endothelial-like cells has been needed, which would have functions similar to normal human intestinal epithelial cells and BMECs. In this review, we describe the development research of small intestinal epithelial cells, intestinal organoids and BMECs differentiated from human iPS cells to construct of drug discovery research support models.
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