Cell Medicine 7(2) Abstracts

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Cell Medicine, Vol. 7, pp. 51–57, 2015
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DOI: http://dx.doi.org/10.3727/215517914X681802
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Synergistic Effects of Calcineurin Inhibitors and Steroids on Steroid Sensitivity of Peripheral Blood Mononuclear Cells

Hironori Takeuchi,* Hitoshi Iwamoto,† Yuki Nakamura,† Toshihiko Hirano,‡ Osamu Konno,† Yu Kihara,† Naokazu Chiba,† Takayoshi Yokoyama,† Kiminori Takano,† Tatsunori Toraishi,§ KiyoshiOkuyama,§ Chie Ikeda,† Sachiko Tanaka,‡ Kenji Onda,‡ Akiko Soga,* Yukiko Kikuchi,* Takashi Kawaguchi,* Shigeyuki Kawachi,† Sakae Unezaki,* and Motohide Shimazu

*Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
†The Fifth Department of Surgery, Hachioji Medical Center, Tokyo Medical University, Hachioji, Tokyo, Japan
‡Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
§Department of Pharmaceutics, Hachioji Medical Center, Tokyo Medical University, Hachioji, Tokyo, Japan

The steroid receptor (SR) complex contains FKBP51 and FKBP52, which bind to tacrolimus (TAC) and cyclophilin 40, which, in turn, bind to cyclosporine (CYA); these influence the intranuclear mobility of steroid–SR complexes. Pharmacodynamicinteractions are thought to exist between steroids and calcineurin inhibitors (CNIs) on the SR complex. We examined the effect of CNIs on steroid sensitivity. Methylprednisolone (MPSL) sensitivity was estimated as the concentration inhibiting mitosis in 50% (IC50) of peripheral blood mononuclear cells and as the area under the MPSL concentration–proliferation suppressive rate curves (CPS-AUC) in 30 healthy subjects. MPSL sensitivity was compared between the additive group (AG) as the MPSL sensitivity that was a result of addition of the proliferation suppressive rate of CNIs to that of MPSL and the mixed culture group (MCG) as MPSL sensitivity of mixed culture with both MPSL and CNIs in identical patients. IC
50 values of MPSL and cortisol sensitivity were examined before and 2 months after CNI administration in 23 renal transplant recipients. IC50 and CPS-AUC values of MPSL were lower in the MCG than in the AG with administration of TAC and CYA. The CPS-AUC ratio of MCG and AG was lower in the TAC group. IC50 values of MPSL and cortisol tended to be lower after administration of TAC and CYA, and a significant difference was observed in the IC50 of cortisol after TAC administration. Steroid sensitivity increased with both TAC and CYA. Furthermore, TAC had a greater effect on increasing sensitivity. Thus, concomitant administration of CNIs and steroids can increase steroid sensitivity.

Key words: Steroid sensitivity; Pharmacodynamic interaction; Calcineurin inhibitors (CNIs); Tacrolimus (TAC); Cyclosporine (CYA)

Received May 21, 2014; final acceptance October 27, 2014. Online prepub date: December 12, 2014.
Address correspondence to Hironori Takeuchi, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Tel/Fax: +81-42-676-5836; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 7, pp. 59–66, 2015
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DOI: http://dx.doi.org/10.3727/215517914X685150
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2015 Cognizant Comm. Corp.
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Improvement of Infusion Process in Cell Transplantation: Effect of Shear Stress on Hepatocyte Viability Under Horizontal and Vertical Syringe Orientation

Sandi Sufiandi,* Hiromichi Obara,*† Shin Enosawa,† Huai-Che Hsu,† Naoto Matsuno,*† and Hiroshi Mizunuma*

*Department of Mechanical Engineering, Graduate School of Science and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo, Japan
†Clinical Research Center, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan

Improving cell viability and function are important for enhancing the clinical results of cell transplantation. The relationship between cell viability and shear stress remains unexplained, and sedimentation effects during the infusion process are important to the hepatocyte transplantation process. In the present study, the relationship between cell viability and shear stress in the presence of sedimentation effect was investigated using a microchannel simulating the cell transplantation process under several shear stress conditions. Horizontal and vertical syringe orientations were employed to investigate the sedimentation effect. The vertical syringe orientation resulted in lower viability loss than the horizontal orientation. In summary, removing a sedimentation effect is important to improving cell viability by preventing high shear stress.

Key words: Hepatocytes; Viability loss; Syringe orientation; Rectangular microchannel; Shear stress

Received May 21, 2014; final acceptance November 18, 2014. Online prepub date: December 12, 2014.
Address correspondence to Hiromichi Obara, Department of Mechanical Engineering, Graduate School of Science and Engineering, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397, Japan. Tel: +81-4-2677-2943; Fax: +81-4-2677-2943; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 7, pp. 67–74, 2015
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DOI: http://dx.doi.org/10.3727/215517914X685187
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2015 Cognizant Comm. Corp.
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Three-Dimensional In Vitro Hepatic Constructs Formed Using Combinatorial Tapered Stencil for Cluster Culture (TASCL) Device

Yoshitaka Miyamoto,*1 Masashi Ikeuchi,†‡1 Hirofumi Noguchi,§ TohruYagi,¶ and Shuji Hayashi*

*Department of Advanced Medicine in Biotechnology and Robotics, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan
†Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
‡PRESTO, Japan Science and Technology (JST), Saitama, Japan
§Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
¶School of Information Science and Engineering, Tokyo Institute of Technology, Tokyo, Japan

Attempts to create artificial liver tissue from various cells have been reported as an alternative method for liver transplantation and pharmaceutical testing. In the construction of artificial liver tissue, the selection of the cell source is the most important factor. However, if an appropriate environment (in vitro/in vivo) cannot be provided for various cells, it is not possible to obtain artificial liver tissue with the desired function. Therefore, we focused on the in vitro environment and produced liver tissues using MEMS technology. In the present study, we report a combinatorial TASCL device to prepare 3D cell constructs in vitro. The TASCL device was fabricated with an overall size of 10 mm × 10 mm with microwells and a top aperture (400 μm × 400 μm, 600 μm × 600μm, 800 μm × 800 μm) and bottom aperture (40 μm × 40 μm, 80 μm × 80 μm, 160 μm × 160 μm) per microwell. The TASCL device can be easily installed on various culture dishes with tweezers. Using plastic dishes as the bottom surface of the combinatorial TASCL device, 3D hepatocyte constructs of uniform sizes (about φ 100 mm–φ 200 mm) were produced by increasing the seeding cell density of primary mouse hepatocytes. The 3D hepatocyte constructs obtained using the TASCL device were alive and secreted albumin. On the other hand, partially adhered primary mouse hepatocytes exhibited a cobblestone morphology on the collagen-coated bottom of the individual microwells using the combinatorial TASCL device. By changing the bottom substrate of the TASCL device, the culture environment of the cell constructs was easily changed to a 3D environment. The combinatorial TASCL device described in this report can be used quickly and simply. This device will be useful for preparing hepatocyte constructs for application in drug screening and cell medicine.

Key words: Primary hepatocytes; Hepatic constructs; Three-dimensional (3D) culture; Tapered stencil for cluster culture (TASCL) device; Biomedical microdevices

Received May 21, 2014; final acceptance November 10, 2014. Online prepub date: December 12, 2014.
1These authors provided equal contribution to this work.
Address correspondence to Yoshitaka Miyamoto, Ph.D., Department of Advanced Medicine in Biotechnology and Robotics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Tel: +81-52-719-1873; Fax: +81-52-719-1977; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 7, pp. 75–82, 2015
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DOI: http://dx.doi.org/10.3727/215517914X685169
Copyright ©
2015 Cognizant Comm. Corp.
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Influence of Autofluorescence Derived From Living Body on In Vivo Fluorescence Imaging Using Quantum Dots

Hiroshi Yukawa,* Masaki Watanabe,† Noritada Kaji,*† and Yoshinobu Baba*†‡

*Research Center for Innovative Nanobiodevices, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan
†Department of Applied Chemistry, Nagoya University, Graduate School of Engineering, Furo-cho, Chikusa-ku, Nagoya, Japan
‡Health Technology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Hayashi-cho, Takamatsu, Japan

Quantum dots (QDs) are thought to be a novel inorganic probe for in vivo fluorescence imaging because of their excellent fluorescence properties. Autofluorescence is generally known to be produced from various living bodies including humans, rats, and mice. However, the influence of the autofluorescence on in vivo fluorescence imaging using QDs remains poorly understood. In this article, we assessed the autofluorescence derived from a mouse body and the influence of the autofluorescence on in vivo fluorescence imaging using QDs. The dorsal and ventral autofluorescence derived from a mouse from which the hair was removed were detected under all kinds of excitation/fluorescence filter settings (blue, green, yellow, red, deep red, and NIR) using theMaestroTM
in vivo imaging system. The degree of autofluorescence was found to be extremely high in the red filter condition, but transplanted ASCs labeled with QDs on the back of a mouse could be detected in the red filter condition. Moreover, the ASCs labeled with QDs could be traced for at least 5 days. We suggest that fluorescence imaging using QDs can be useful for the detection of transplanted cells.

Key words: Autofluorescence; Quantum dots (QDs); In vivo imaging; Adipose tissue-derived stem cells (ASCs)

Received May 21, 2014; final acceptance December 3, 2014. Online prepub date: December 12, 2014.
Address correspondence to Hiroshi Yukawa, Research Center for Innovative Nanobiodevices, Nagoya University, Furo-cho, Chikusa-kuqNagoya 464-8603, Japan. Tel: +81-52-789-5654; Fax: +81-52-789-3560; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 7, pp. 83–93, 2015
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DOI: http://dx.doi.org/10.3727/215517914X685169
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Potential Factors for the Differentiation of ESCs/iPSCs Into Insulin-Producing Cells

Takako Tsugata,* Naruo Nikoh,* Tatsuya Kin,† Issei Saitoh,‡ Yasufumi Noguchi,§ Hideo Ueki,¶ Masami Watanabe,¶ Andrew M. James Shapiro,† and Hirofumi Noguchi*#

*Natural and Environmental Sciences Program, The Open University of Japan, Chiba, Japan
†Clinical Islet Transplant Program, University of Alberta, Edmonton, Alberta, Canada
‡Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University, Niigata, Japan
§Department of Socio-environmental Design, Hiroshima International University, Hiroshima, Japan
¶Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
#Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan

The low efficiency of in vitro differentiation of human embryonic stem cells (ESCs) or human induced pluripotent stem cells (iPSCs) into insulin-producing cells thus creates a crucial hurdle for the clinical implementation of human pluripotent stem cells (PSCs). In this study, we investigated the key factors for the differentiation of PSCs into insulin-producing cells. We obtained microarray data of HUES8 and HUES6 from two GeneChips (GPL3921: Affymetrix HT Human Genome U133A Array, GPL570:Affymetrix Human Genome U133 Plus 2.0 Array) in a database of GEO (NCBI), since HUES8 can differentiate into pancreatic cells, while HUES6 hardly demonstrates any differentiation at all. The genes with more than fourfold higher expressions in HUES8 compared to HUES6 included RPS4Y1DDX3YEIF1AYGREM1GATA6, and NLGN4Y. Since there were four genes, RPS4Y1DDX3YEIF1AY, and NLGN4Y, on the Y chromosome and HUES8 was a male cell line and HUES6 was a female cell line, we excluded these genes in this study. On the other hand, genes with more than fourfold higher expressions in HUES6 compared to HUES8 included NLRP2EGR1, and SMC3. We next compared iPSCs derived from pancreatic cells (PiPSCs) and iPSCsderived from fibroblasts (FiPSCs). PiPSCs differentiated into insulin-producing cells more easily than FiPSCs because of their epigenetic memory. The gene expressions of GREM1GATA6NLRP2EGR1, and SMC3 in PiPSCs and FiPSCs were also investigated. The expression level of GREM1 and GATA6 in PiPSCs were higher than in FiPSCs. On the other hand, EGR1, which was lower in HUES8 than in HUES6, was predictably lower in PiPSCs than FiPSCs, while NLRP2 and SMC3 were higher inPiPSCs than FiPSCs. These data suggest that the expression of GATA6 and GREM1 and the inhibition of EGR1 may be important factors for the differentiation of PSCs into insulin-producing cells.

Key words: Embryonic stem cells (ESCs); Induced pluripotent stem cells (iPSCs); GATA6GREM1EGR1

Received May 21, 2014; final acceptance November 7, 2014. Online prepub date: December 12, 2014.
Address correspondence to Hirofumi Noguchi, M.D., Ph.D., Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. Tel/Fax: +81-98-895-3331; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or This e-mail address is being protected from spambots. You need JavaScript enabled to view it