The development of methods to make changes in the property of induced pluripotent stem cells by the intermittent or sustained hypoxia.

• Project/Area Number: 23659109
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Kyoto University
• Principal Investigator: CHIN Kazuo 京都大学, 医学(系)研究科(研究院), 教授 (90197640)
• Co-Investigator(Kenkyū-buntansha): TOGUCHIDA Junya (SATO Yukiyasu) 京都大学, 再生委科学研究所, 教授 (40273502) ; HOSHINO Yuma 京都大学, 医学(系)研究科(研究院), 助教 (00378746) ; 佐藤 幸保 京都大学, 医学(系)研究科(研究院), 非常勤講師 (00508236) ; 谷澤 公伸 京都大学, 医学(系)研究科(研究院), 助教 (20639140)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: intermittent hypoxia, / sustained hypoxia, / pluripotent stem cell, / BEAD-2B cell, / hypoxemia, / hypertension, / lipid metabolism, / sleepiness. / 再生医学 / 細胞・組織 / 低酸素 / 間欠的低酸素 / 持続的低酸素

Research Abstract

We developed a new hypoxia exposure apparatus for cellular experiments to produce intermittent and sustained hypoxia (IH and SH). We found that IH prevented cellular wound healing in BEADS-2B cells. At appliance, we aimed to develop a new method of altering the natures of induced pluripotent stem cells (iPS cells). However, we have not achieved our primary aim because preliminary studies took more time than planned. Firstly, we needed to develop a new hypoxia exposure apparatus by ourselves because our previous hypoxia exposure apparatus at appliance could not reproduce the stable hypoxic status. Secondly, it was also difficult to acquire sufficient iPS cells because producing iPS cells took much time. We also conducted clinical researches of sleep apnea syndrome, which patients showed intermittent hypoxemia in vivo, to seek for novel biomarkers for IH and investigate the relationships between IH and hypertension, lipid metabolism and sleepiness.

Research Products

• [Journal Article] A urine biomarker for severe obstructive sleep apnoea patients : lipocalin-type prostaglandin D synthase (2013)
  • Author(s): Chihara Y, Chin K, Aritake K, Harada Y, Toyama Y, Murase K, Yoshimura C, Hitomi T, Oga T, Mishima M, Urade Y
  • Journal Title: Eur Respir J Volume: 42 Pages: 1563-74
• [Journal Article] Kadotani H. Association between sleep apnea, sleep duration, and serum lipid profile in an urban, male, working population in Japan (2013)
  • Author(s): Toyama Y, Chin K, Chihara Y, Takegami M, Takahashi K, Sumi K, Nakamura T, Nakayama-Ashida Y, Minami I, Horita S, Oka Y, Wakamura T, Fukuhara S, Mishima M
  • Journal Title: Chest Volume: 143 Pages: 720-8
• [Journal Article] Association between plasma neutrophil gelatinase associated lipocalin level and obstructive sleep apnea or nocturnal intermittent hypoxia (2013)
  • Author(s): Murase K, Mori K, Yoshimura C, Aihara K, Chihara Y, Azuma M, Harada Y, Toyama Y, Tanizawa K, Handa T, Hitomi T, Oga T, Mishima M, Chin K
  • Journal Title: PLoS One Volume: 8
  • NAID: 120005241417
• [Journal Article] Flexible positive airway pressure improves treatment adherence compared with auto-adjusting PAP (2013)
  • Author(s): Chihara Y, Tsuboi T, Hitomi T, Azuma M, Murase K, Toyama Y, Harada Y, Aihara K, Tanizawa K, Handa T, Yoshimura C, Oga T, Yamamoto K, Mishima M, Chin K
  • Journal Title: Sleep Volume: 36 Pages: 229-36
• [Journal Article] A urine biomarker for severe OSA patients: lipocaline-type prostaglandin D synthase. (2013)
  • Author(s): Chihara Y, Chin K, Aritake K, Harada Y, Toyama Y, Murase K, Yoshimura C, Hitomi T, Oga T, Mishima M, Urade Y.
  • Journal Title: Eur Respir J Volume: in press Issue: 6 Pages: 1563-1574
  • DOI: 10.1183/09031936.00133512
  • Peer Reviewed
• [Journal Article] Association between plasma neutrophil gelatinase associated lipocalin level and obstructive sleep apnea or nocturnal intermittent hypoxia (2013)
  • Author(s): Murase K, Mori K, Yoshimura C, Aihara K, Chihara Y, Azuma M, Harada Y, Toyama Y, Tanizawa K, Handa T, Hitomi T, Oga T, Mishima M, Chin K
  • Journal Title: PLoS One Volume: 8 Issue: 1 Pages: e54184-e54184
  • DOI: 10.1371/journal.pone.0054184
  • NAID: 120005241417
  • Peer Reviewed
• [Journal Article] Association between sleep apnea, sleep duration and serum lipid profile in an urban male working population in Japan (2013)
  • Author(s): Toyama Y, Chin K, Kadotani H, et al
  • Journal Title: Chest Volume: 143(3) Issue: 3 Pages: 720-8
  • DOI: 10.1378/chest.12-0338
  • Peer Reviewed
• [Journal Article] Flexible positive airway pressure improves treatment adherence compared with auto-adjusting PAP (2013)
  • Author(s): Chihara Y, Tsuboi T, Hitomi T, Azuma M, Murase K, Toyama Y, Harada Y, Aihara K, Tanizawa K, Handa T, Yoshimura C, Oga T, Yamamoto K, Mishima M, Chin K
  • Journal Title: Sleep Volume: 36:229-36 Issue: 2 Pages: 229-236
  • DOI: 10.5665/sleep.2378
  • Peer Reviewed
• [Journal Article] Differences in relationships among sleep apnoea, glucose level, sleep duration and sleepiness between persons with and without type 2 diabetes (2012)
  • Author(s): Harada Y, Oga T, Chin K, Takegami M, Takahashi K, Sumi K, Nakamura T, Nakayama-Ashida Y, Minami I, Horita S, Oka Y, Wakamura T, Fukuhara S, Mishima M, Kadotani H
  • Journal Title: Journal of Sleep Research Volume: 21 Issue: 4 Pages: 538-543
  • DOI: 10.1111/j.1365-2869.2012.00997.x
  • Peer Reviewed
• [Journal Article] Effects of the presence of hypertension on the relationship between obstructive sleep apnoea and sleepiness (2011)
  • Author(s): Harada Y, Oga T, Chin K, Takegami M, Takahashi K, Sumi K, Nakamura T, Nakayama-Ashida Y, Minami I, Horita S, Oka Y, Wakamura T, Fukuhara S, Mishima M, Kadotani H
  • Journal Title: J Sleep Res Volume: 20 Pages: 538-543
• [Presentation] 閉塞性睡眠時無呼吸と脂肪肝含量の関連の検討 (2013)
  • Author(s): 外山善朗
  • Organizer: 日本睡眠学会第38回定期学術集会アブストラクトシンポジウム2
  • Place of Presentation: 秋田市
  • Year and Date: 2013-06-27
• [Presentation] 閉塞性睡眠時無呼吸と肝脂肪含量の関連の検討 (2013)
  • Author(s): 外山善朗
  • Organizer: 日本睡眠学会第38回定期学術集会 アブストラクトシンポジウム2
  • Place of Presentation: 秋田市
• [Presentation] 睡眠時無呼吸と脂質代謝、脂肪肝 (2013)
  • Author(s): 外山善朗
  • Organizer: 第53回日本呼吸器学会学術講演会 シンポジウム15
  • Place of Presentation: 東京
• [Presentation] Associations between lifestyle-related diseases, sleep apnea and sleep duration (2012)
  • Author(s): Chin K
  • Organizer: The 8th International Symposium on Respiratory Diseases and ATS in China Forum 2012
  • Place of Presentation: Shanghai, China
  • Year and Date: 2012-11-08
  • Invited
• [Presentation] 肥満症と睡眠時無呼吸 (2012)
  • Author(s): 陳和夫
  • Organizer: 第33回日本肥満学会教育講演
  • Place of Presentation: 京都市
  • Year and Date: 2012-10-12
  • Invited
• [Presentation] 睡眠時無呼吸の病態と治療効果 (2012)
  • Author(s): 陳和夫
  • Organizer: 日本内科学会第46回近畿支部生涯教育講演会
  • Place of Presentation: 大阪市
  • Year and Date: 2012-06-27
  • Invited
• [Presentation] Visceral fat accumulation in subjects with non-to-moderate and severe obstructive sleep apnea (2012)
  • Author(s): Chin K, Harada Y, Oga T, Azuma M, Murase K, Toyama Y, Aihara K, Tanizawa K, Chihara Y, Yoshimura C, Hitomi T, Handa T, Mishima M
  • Organizer: American Thoracic Society International Conference 2012
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-05-23
• [Presentation] A possible specific urine biomarker for severe obstructive sleep apnea and cardiovascular diseases : lipocalin-type prostaglandin D synthase (L-PGDS) (2012)
  • Author(s): Chin K, Chihara Y, Aritake K, Harada Y, Azuma M, Toyama Y, Murase K, Aihara K, Tanizawa K, Handa T, Yoshimura C, Hitomi T, Oga T, Mishima M, Hayaishi O, Urade Y
  • Organizer: American Thoracic Society International Conference 2012
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-05-20
• [Presentation] A Possible Specific Urine Biomarker For Severe Obstructive Sleep Apnea And Cardiovascular Diseases-Lipocalin-Type Prostaglandin D Synthase (L-PGDS). (2012)
  • Author(s): Chin K, Chihara Y, Aritake K, Harada Y, Azuma M, Toyama Y, Murase K, Aihara K, Tanizawa K, Handa T, Yoshimura C, Hitomi T, Oga T, Mishima M, Hayaishi O, Urade Y.
  • Organizer: American Thoracic Society International Conference 2012
  • Place of Presentation: San Francisco, USA
• [Presentation] Visceral Fat Accumulation in Subjects with Non-to-moderate and Severe Obstructive Sleep Apnea. (2012)
  • Author(s): Chin K, Harada Y, Oga T, Azuma M, Murase K, Toyama Y, Aihara K, Tanizawa K, Chihara Y, Yoshimura C, Hitomi T, Handa T, Mishima M.
  • Organizer: American Thoracic Society International Conference 2012
  • Place of Presentation: San Francisco, USA
• [Presentation] 肥満症と睡眠時無呼吸 (2012)
  • Author(s): 陳和夫
  • Organizer: 第33回日本肥満学会 教育講演
  • Place of Presentation: 京都市
  • Invited
• [Presentation] Associations between lifestyle-related diseases, sleep apnea and sleep duration. (2012)
  • Author(s): Chin K
  • Organizer: The 8th International Symposium on Respiratory Diseases & ATS in China Forum 2012
  • Place of Presentation: Shanghai, China
  • Invited
• [Presentation] Effects of intermittent hypoxia on several parameters for cardiovascular risk factors. (2011)
  • Author(s): Tanizawa K, Chin K
  • Organizer: Industrial Symposium 4 Metabolic risk of sleep apnea. Worldsleep 2011
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-10-18
• [Presentation] Effects of intermittent hypoxia on several parameters for cardiovascular risk factors. (2011)
  • Author(s): Tanizawa K, Chin K
  • Organizer: Industrial Symposium 4: Metabolic risk of sleep apnea.Worldsleep2011(招待講演)
  • Place of Presentation: 京都国際会議場（京都府）
• [Remarks] 特になし。