Neural stem cell transplantation for refractory idiopathic or diabetic gastroparesis

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659103
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General physiology
• Research Institution: Keio University
• Principal Investigator: SUZUKI Hidekazu 慶應義塾大学, 医学部, 准教授 (70255454)
• Co-Investigator(Kenkyū-buntansha): URAOKA Toshio 慶應義塾大学, 医学部, 講師 (80448216) ; KAWASE Satoshi 慶應義塾大学, 医学部, 特任助教 (80468496) ; YAHAGI Naohisa 慶應義塾大学, 医学部, 教授 (90292937)
• Research Collaborator: FUKUHARA Seiichiro 慶應義塾大学, 医学部, 大学院生 ; MASAOKA Tastuhiro 慶應義塾大学, 医学部, 助教 ; UCHIDA Masayuki 明治乳業研究所, 食機能科学研究所, リーダー ; NISHIMURA Soraya 慶應義塾大学, 医学部, 大学院生
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 胃不全麻痺 / 糖尿病 / 脂質異常症 / アポプロテインE / 胃排出 / 神経幹細胞 / 神経幹細胞移植

Research Abstract

Delayed gastric emptying was observed in 27 % of db/db mouse with a significant decrease in the serum ApoE level and in the myenteric nNOS and GFAP expression. The gastric emptying was also significantly delayed in ApoE knockout (KO) mouse with a decrease in the expression of nNOS and GFAP in myenteric plexus. Transplantation of neural stem cells (NSCs) improved delayed gastric emptying in nNOS KO mice and ApoE KO mise. The expressions of nNOS and GFAP in myenteric plexus were restored by transplantation of NSCs. Transplantation of NSCs restored the delayed gastric emptying in apoE knockout mice, suggesting a promising application of regenerative therapy against gastroparesis and a possible development of serum ApoE as a potential biomarker for gastrointestinal motility disorders.

Research Products

• [Journal Article] Randomised clinical trial : rikkunshito in the treatment of functional dyspepsia–a multi-centre, double-blind, randomised, placebo-controlled study (2014)
  • Author(s): Suzuki, H., Matsuzaki, J., Fukushima, Y., Suzaki, F., Kasugai, K., Nishizawa, T., Naito, Y., Hayakawa, T., Kamiya, T., Andoh, T., Yoshida, H., Tokura, Y., Nagata, H., Kobayakawa, M., Mori, M., Kato, K., Hosoda, H., Takabayashi, T., Miura, S., Uemura, N., Joh, T., Hibi, T., Tack, J.
  • Journal Title: Neurogastr oenterol. Motil. Volume: (Epub)
  • DOI: 10.1111/nmo.12348.[Epub]
• [Journal Article] Greater loss of productivity among Japanese workers with gastroesophageal reflux disease (GERD) symptoms that persist vs resolve on medical therapy (2014)
  • Author(s): Suzuki, H., Matsuzaki, J., Masaoka, T., Inadomi, J.M.
  • Journal Title: Neurogastr oenterol. Motil. Volume: (Epub)
  • DOI: 10.1111/nmo.12319.[Epub]
• [Journal Article] ヘリコバクター・ピロリ感染胃炎と機能性ディスペプシア (2014)
  • Author(s): 鈴木秀和
  • Journal Title: 日本ヘリコバクター学会誌 Volume: 15(2) Pages: 56-61
• [Journal Article] Effect of lansoprazole on the epigastric symptoms of functional dyspepsia (ELF study) : a multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial (2013)
  • Author(s): Suzuki, H., Kusunoki, H., Kamiya, T., Futagami, S., Yamaguchi, Y., Nishizawa, T., Iwasaki, E., Matsuzaki, J., Takahashi, S., Sakamoto, C., Haruma, K., Joh, T., Asakura, K., Hibi, T.
  • Journal Title: ueg journal Volume: 1(6) Pages: 445-452
  • DOI: 10.1177/2050640613510904
• [Journal Article] CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence (2013)
  • Author(s): Hirata, K., Suzuki, H., Imaeda, H., Matsuzaki, J., Tsugawa, H., Nagano, O., Asakura, K., Saya, H., Hibi, T.
  • Journal Title: Br . J. Cancer. Volume: 109(2) Pages: 379-86
  • DOI: 10.1038/bjc.2013.314
• [Journal Article] Validation of the GerdQ questionnaire for the management of gastroesophageal reflux disease in Japan (2013)
  • Author(s): Suzuki, H., Matsuzaki, J., Okada, S., Fukuhara, S., Hirata, K., Hibi, T.
  • Journal Title: ueg journal Volume: 1(3) Pages: 175-183
  • DOI: 10.1177/2050640613485238
• [Journal Article] Impaired heme oxygenase-1 induction in the gastric antrum induces disruption of the interstitial cells of Cajal network in a rat model of streptozotocin-induced diabetes (2013)
  • Author(s): Mogami, S., Suzuki, H., Tsugawa, H., Fukuhara, S., Hibi, T.
  • Journal Title: Neurogastr oenterol. Motil. Volume: 25(7) Pages: 609-e465
  • DOI: 10.1111/nmo.12122
• [Journal Article] Helicobacter pylori infection in functional dyspepsia (2013)
  • Author(s): Suzuki, H., Moayyedi, P.
  • Journal Title: Natur e Rev. Gastroenter ol. Hepatol. Volume: 10(3) Pages: 168-74
  • DOI: 10.1038/nrgastro.2013.9
• [Journal Article] Helicobacter pylori CagAを分解するROS誘導性オートファジーはCD44v9発現がん幹細胞で抑制されCagAが蓄積する (2013)
  • Author(s): 津川仁,鈴木秀和
  • Journal Title: 細胞工学 Volume: 32(3) Pages: 324-325
• [Journal Article] 機能性ディスペプシア (2013)
  • Author(s): 鈴木秀和,西澤俊宏,日比紀文
  • Journal Title: 日本内科学会雑誌 Volume: 102(1) Pages: 63-69
• [Journal Article] CDX1 confers intestinal phenotype on gastric epithelial cells via induction of stemness-associated reprogramming factors SALL4 and KLF5 (2012)
  • Author(s): Fujii, Y., Yoshihashi, K., Suzuki, H., Tsutsumi, S., Mutoh, H., Maeda, S., Aburatani, H., Hatakeyama, M.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 109(50) Pages: 20584-20589
  • DOI: 10.1073/pnas.1208651109
• [Journal Article] Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells (2012)
  • Author(s): Tsugawa, H., Suzuki, H., Saya, H., Hatakeyama, M., Hirayama, T., Hirata, K., Nagano, O., Matsuzaki, J., Hibi, T.
  • Journal Title: Cell Host Microbe Volume: 12(6) Pages: 764-777
  • DOI: 10.1016/j.chom.2012.10.014.
• [Journal Article] High frequency of overlap between functional dyspepsia and overactive bladder (2012)
  • Author(s): Matsuzaki, J., Suzuki, H., Fukushima, Y., Hirata, K., Fukuhara, S., Okada, S., Hibi, T.
  • Journal Title: Neurogastr oenterol. Motil. Volume: 24(9) Pages: 821-7
  • DOI: 10.1111/j.1365-2982.2012.01939.x
• [Journal Article] Efficacy of solifenacin on irritable bowel syndrome with diarrhea (IBS-D) : open-label prospective pilot trial. J (2012)
  • Author(s): Fukushima, Y., Suzuki, H., Matsuzaki, J., Kiyosue, A., Hibi, T.
  • Journal Title: Neurogastr oenterol. Motil. Volume: 18(3) Pages: 317-323
  • DOI: 10.5056/jnm.2012.18.3.317.
• [Journal Article] Effects ofβ-(1,3-1,6)-D-glucan on irritable bowel syndrome-related colonic hypersensitivity (2012)
  • Author(s): Asano, T., Tanaka, K., Suemasu, S., Ishihara, T., Tahara, K., Suzuki, T., Suzuki, H., Fukudo, S., Mizushima, T.
  • Journal Title: Biochem. Biophys. Res. Com. Volume: 420(2) Pages: 444-9
  • DOI: 10.1016/j.bbrc.2012.03.015
• [Journal Article] Classification of functional dyspepsia based on concomitant bowel symptoms (2012)
  • Author(s): Matsuzaki, J., Suzuki, H., Asakura, K., Fukushima, Y., Inadomi, J.M., Takebayashi, T., Hibi, T.
  • Journal Title: Neurogastr oenterol. Motil. Volume: 24(4) Pages: 325-e164
  • DOI: 10.1111/j.1365-2982.2011.01859.x
• [Journal Article] Reduced ghrelin production induced anorexia after rat gastric ischemia and reperfusion (2012)
  • Author(s): Mogami, S., Suzuki, H., Fukuhara, S., Matsuzaki, J., Kangawa, K., Hibi, T.
  • Journal Title: Am. J . Physiol. Gastrointest. Liver Physiol. Volume: 302(3) Pages: G359-64
  • DOI: 10.1152/ajpgi.00297.2011
• [Journal Article] Enhanced gastric ghrelin production and secretion in rats with gastric outlet obstruction (2012)
  • Author(s): Iwasaki, E., Suzuki, H., Masaoka, T., Nishizawa, T., Hosoda, H., Kangawa, K., Hibi, T.
  • Journal Title: Dig. Dis. Sci. Volume: 57(4) Pages: 858-864
  • DOI: 10.1007/s10620-011-1953-y
• [Presentation] 脂質代謝に関与するアポリポプロテインEの動態変化に伴う胃運動及び胃壁内神経叢への影響 (2014)
  • Author(s): 福原誠一郎、正岡建洋、鈴木秀和
  • Organizer: シンポジウム8「生活習慣病と消化器疾患・病態生理学の新たな展開.第100回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-23
• [Presentation] Impairment of apolipoprotein E evokes delayed gastric emptying through nitrergic dysfunction (2014)
  • Author(s): Fukuhara, S., Suzuki, H., Masaoka, T., Tsugawa, H., Okada, S., Mori, H., Hirata, K., Matsuzaki, J., Iwasaki, E., Mizushima, T., Suzuki, M.
  • Organizer: The 7th Inter national Gastrointestinal Consensus Symposium (IGICS)"Gastrointestinal Function and Diseases", The 10^<th> J GA
  • Place of Presentation: Fukushima, Japan
  • Year and Date: 2014-02-15
• [Presentation] Involvement of stemness factors in the intestinal transdifferentiation of gastric epithelial cells (2013)
  • Author(s): Fujii, Y., Suzuki, H., Aburatani, H., Hatakayama, M.
  • Organizer: "The latest advances in gastr ic cancer research, from basic science to therapeutics", The 4^<th> J CA-AACR Special Joint Conference
  • Place of Presentation: Urayasu, Japan
  • Year and Date: 2013-12-17
• [Presentation] Escaped autophagy of H. pylori-derived oncoprotein CagA in gastric cancer stem-like cells (2013)
  • Author(s): Suzuki, H.
  • Organizer: Session 5"Cancer stem cells (2)""The latest advances in gastr ic cancer research, from basic science to therapeutics", The 4^<th> J CA-AACR Special Joint Conference
  • Place of Presentation: Urayasu, Japan
  • Year and Date: 2013-12-13
• [Presentation] 実験動物を用いたグレリン動態と胃排出障害 (2013)
  • Author(s): 岩崎栄典、鈴木秀和、最上祥子、正岡建洋、金井隆典、塚田信廣
  • Organizer: シンポジウム10「brain-gutペプチドの病態生理学」第50回記念日本臨床生理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-09
• [Presentation] The dynamics of aquaporin-4 in the stomach of histamine type 2 receptor knockout mice and Helicobacter pylori infection (2013)
  • Author(s): Fukuhara, S., Masaoka, T., Suzuki, H., Matsuzaki, J., Saito,Y., Tsugawa, H., Hirata, K., Okada, S., Mori, H., Yasui, M., Hibi, T.
  • Organizer: The 15^<th> Taishotoyama Inter national Symposium on Gastroenterology
  • Place of Presentation: Tokyo
  • Year and Date: 2013-09-27
• [Presentation] Symposium (Steps towar ds gastr ic cancer ) Lecture"Role of microRNA and cancer stem cells in gastric carcinogenesis" (2013)
  • Author(s): Suzuki, H.
  • Organizer: The XXVI^<th> Inter national Workshop on Helicobacter and related bacter ia in chronic digestive inflammation and gastr ic cancer
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2013-09-13
• [Presentation] Application of ^<13>C-acetic acid breath test for animals with impaired gastric motility (2013)
  • Author(s): Fukuhara, S., Suzuki, H., Masaoka, T., Suemasu, S., Matsuzaki, J., Tsugawa, H., Okada, S., Hirata, K., Mori, H., Saito, Y., Mizushima, T., Hibi, T.
  • Organizer: Digestive Disease Week 2013
  • Place of Presentation: Florida, U.S.A.
  • Year and Date: 2013-05-21
• [Presentation] The Loss of Work Productivity Associated with Gastroesophageal Reflux Disease(GERD) in a Japanese Working Population (2013)
  • Author(s): Suzuki, H., Matsuzaki, J., Masaoka, T., Okada, S., Inadomi, J., Hibi, T.
  • Organizer: Digestive Disease Week 2013
  • Place of Presentation: Florida, U.S.A.
  • Year and Date: 2013-05-21
• [Presentation] Expression of CD44 Variant 9 Contributes to 5-Fluorouracil Resistance in Gastric Cancer Trough Anti-Oxidative Stress Mechanism (2013)
  • Author(s): Okada, S., Suzuki, H., Masaoka, T., Tsugawa, H., Matsuzaki, J., Fukuhara, S., Hirata, K., Mori, H., Saya, H., Hibi, T.
  • Organizer: Digestive Disease Week 2013
  • Place of Presentation: Florida, U.S.A.
  • Year and Date: 2013-05-19
• [Presentation] 消化管機能異常モデルにおけるグレリンと胃運動との関係 (2013)
  • Author(s): 最上祥子、鈴木秀和、福原誠一郎、正岡建洋、松崎潤太郎、津川仁、日比紀文
  • Organizer: ワークショップ5「消化管ホルモン研究の基礎と臨床」第9回日本消化管学会総会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2013-01-25
• [Presentation] The Role of Helicobacter pylori infection in the disease entity of functional dyspepsia (2012)
  • Author(s): Suzuki, H.
  • Organizer: Symposium 7"Current Issues on Functional Dyspepsia". Seoul Inter national Digestive Disease Symposium 2012 (SIDDS2012)
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2012-11-23
• [Presentation] Eradication of Helicobacter pylori with 10-day sitafloxacin-based triple therapy as a third- or fourth-line rescue therapy : preliminary results of open-label randomized trial (2012)
  • Author(s): Mori, H., Suzuki, H., Matsuzaki, J.,Tsugawa, H., Fukuhara, S., Okada, S., Hirata, K., Hibi, T.
  • Organizer: The Amer ican College of Gastroenterology Annual Scientific Meeting (ACG2012)
  • Place of Presentation: Las Vegas, USA
  • Year and Date: 2012-10-23
• [Presentation] Improvement in the quality of life related to reflux symptoms after Helicobacter pylori eradication therapy (2012)
  • Author(s): Hirata, K., Suzuki, H., Matsuzaki, J., Masaoka, T., Saito, Y., Nishizawa, T., Iwasaki, E., Fukuhara, S., Okada, S., Hibi, T.
  • Organizer: 2012 J oint Inter national Neurogastroenterology and Motility Meeting
  • Place of Presentation: Bologna, Italy
  • Year and Date: 2012-09-08
• [Presentation] The GerdQ is a useful tool for evaluating the patients'satisfaction and identifying the patients with"unmet medical needs" (2012)
  • Author(s): Okada, S., Suzuki, H., Matsuzaki, J., Fukuhara, S., Hirata, K., Hibi, T.
  • Organizer: 2012 J oint Inter national Neurogastroenterology and Motility Meeting
  • Place of Presentation: Bologna, Italy
  • Year and Date: 2012-09-08
• [Presentation] High frequency of overlap between functional dyspepsia, irritable bowel syndrome and overactive bladder (2012)
  • Author(s): Suzuki, H., Matsuzaki, J., Fukushima, Y., Hirata, K., Fukuhara, S., Okada, S., Hibi, T.
  • Organizer: 2012 J oint Inter national Neurogastroenterology and Motility Meeting
  • Place of Presentation: Bologna, Italy
  • Year and Date: 2012-09-07
• [Presentation] Impaired heme oxygenase-1 upregulation induced decreased interstitial cells of Cajal in streptozotocin-induced diabetes model (2012)
  • Author(s): Mogami, S., Suzuki, H., Tsugawa, H., Matsuzaki, J., Hibi, T.
  • Organizer: The 14^<th> Meeting of International Conference on Ulcer Research (ICUR)
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2012-07-13
• [Presentation] Evaluation of CD44 variant expression as a recurrence marker of gastric cancer after endoscopic submucosal dissection (2012)
  • Author(s): Hirata, K., Suzuki, H., Saya, H., Imaeda, H., Nagano, O., Tsugawa, H., Matsuzaki, J., Okada, S., Fukuhara, S., Mukai, M., Hibi, T.
  • Organizer: The 10^<th> annual meeting of the Inter national Society for Stem Cell Research (ISSCR)
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2012-06-14
• [Presentation] Dysfunctional gastric emptying with downregulation of muscle-specific microRNAs in Helicobacter pylori -infected mice (2012)
  • Author(s): Saito, Y., Suzuki, H., Tsugawa, H., Suzuki, S., Matsuzaki, J., Hirata. K., Saito, H,, Hibi, T.
  • Organizer: The 2nd Asian Pacific Topic Conference, Asian Pacific Helicobacter pylori Meeting 2012
  • Place of Presentation: Kuala Lumpur, Malaysia
  • Year and Date: 2012-06-14
• [Book] Oxidative stress in stomach cancer CANCER:OXIDATIVE STRESS AND DIETARY ANTIOXIDANTS (eds.) Victor R. Preedy, (ISBN :978-0-12-405205-5) (2014)
  • Author(s): Suzuki, H., Nishizawa, T.
  • Total Pages: 33-40
  • Publisher: Academic Press
• [Book] 胃・十二指腸の運動の特徴とその制御.専門医のための消化器病学第2版 (2013)
  • Author(s): 正岡建洋,鈴木秀和
  • Total Pages: 74-75
  • Publisher: 医学書院東京
• [Book] 糖尿病性胃麻痺の病態機序の解明と新規治療戦略『ナテグリニド記念豊島研究教育資金平成14年度～23年度事業報告集』 (2012)
  • Author(s): 鈴木秀和,福原誠一郎,松崎潤太郎,岡田佐和子,津川仁,最上祥子,斎藤義正, Jan F. Tack,河瀬聡,岡野栄之
  • Total Pages: 178-183
  • Publisher: ナテグリニド記念豊島研究教育資金運営委員会