Construction of medicine for radiation emergency system using iPS cell bank

• Project/Area Number: 25670762
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Hiroshima University
• Principal Investigator: Higashi Yukihito 広島大学, 原爆放射線医科学研究所, 教授 (40346490)
• Co-Investigator(Kenkyū-buntansha): NOMA KENSUKE 広島大学, 原爆放射線医科学研究所, 助教 (00379893) ; NAKASHIMA AYUMU 広島大学, 原爆放射線医科学研究所, 特任助教 (40448262)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 緊急被ばく医療 / 再生医療 / 細胞バンク / 再生療法

Outline of Final Research Achievements

In order to develop a regenerative medical system, by using the existing one, for radiation emergency, we attempted to manage the cell processing center to establish a system of a safe and secured iPS cell bank for radiation medicine. By using this iPS cell bank as the central leverage, we developed an education program for radiation emergency medicine, and to put this education program in practice, and to construct a network of regenerative medicine for radiation emergency medicine. We planed the trategies for promoting basic research and clinical research for radiation emergency medicine through international collaboration. Systematic promotion of the establishment of new therapies by comprehensively using cell therapy, cellular repair and regenerative biotechnology through collaboration with the medical experts in various fields such as teaching staff, including those in basic research, and graduate students, post-docs, research coordinators, doctors, nurses, etc.

Research Products

• [Journal Article] A combination of flow-mediated vasodilation combined with nitroglycerine-induced vasodilation is more useful for prediction of cardiovascular events. (2016)
  • Author(s): Kajikawa M, Maruhashi T, Hida E, Iwamoto Y, Matsumoto T, Iwamoto A, Oda N,Kishimoto S, Matsui S, Hidaka T, Kihara Y, Chayama K, Goto C, Aibara Y, Nakashima A, Noma K, Higashi Y.
  • Journal Title: Hypertension. Volume: 67(5) Pages: 1045-1052
  • DOI: 10.1161/hypertensionaha.115.06839
  • Peer Reviewed / Open Access
• [Journal Article] Ratio of serum levels of AGEs to soluble form of RAGE Is a predictor of endothelial function. (2015)
  • Author(s): Kajikawa M, Nakashima A, Fujimura N, Maruhashi T, Iwamoto Y, Iwamoto A, Matsumoto T, Oda N, Hidaka T, Kihara Y, Chayama K, Goto C, Aibara Y, Noma K, Takeuchi M, Matsui T, Yamagishi S, Higashi Y.
  • Journal Title: Diabetes Care Volume: 38(1) Pages: 119-125
  • DOI: 10.2337/dc14-1435
  • Peer Reviewed
• [Journal Article] mpact of aldosterone-producing adenoma on endothelial function and Rho-associated kinase activity in patients with primary aldosteronism. (2015)
  • Author(s): Matsumoto T, Oki K, Kajikawa M, Nakashima A, Maruhashi T, Iwamoto Y, Iwamoto A, Oda N, Hidaka T, Kihara Y, Kohno N, Chayama K, Goto C, Aibara Y, Noma K, Liao JK, Higashi Y.
  • Journal Title: Hypertension. Volume: 65(4) Pages: 841-8
  • DOI: 10.1161/hypertensionaha.114.05001
  • Peer Reviewed / Open Access
• [Journal Article] Exogenous nitric oxide inhibits ROCK activity in patients with angina pectoris: a randomized controlled trial. (2015)
  • Author(s): Maruhashi T, Noma K, Fujimura N, Kajikawa M, Matsumoto T, Hidaka T, Nakashima A, Kihara Y, Liao JK, Higashi Y.
  • Journal Title: Hypertens Res. Volume: 38(7) Pages: 485-490
  • DOI: 10.1038/hr.2015.24
  • Peer Reviewed
• [Journal Article] Endothelial dysfunction is associated with the severity of cerebral small vessel disease (2015)
  • Author(s): Nezu T, Hosomi N, Aoki S, Sugimoto T, Kubo S, Araki M, Matsushima H, Mukai T, Takahashi T, Maruyama H, Higashi Y, Matsumoto M.
  • Journal Title: Hypertension Research Volume: 38 Pages: 291-297
  • DOI: 10.1038/hr.2015.4
  • Peer Reviewed
• [Journal Article] Assessment of Endothelial Function (2015)
  • Author(s): Higashi Y.
  • Journal Title: Int. Heart J. Volume: 56 Issue: 2 Pages: 125-134
  • DOI: 10.1536/ihj.14-385
  • NAID: 130004941304
  • Peer Reviewed / Open Access
• [Journal Article] Depletion of Uric Acid Due to SLC22A12 (URAT1) Loss-of-Function Mutation Causes Endothelial Dysfunction in Hypouricemia (2015)
  • Author(s): Sugihara S, Hisatome I, Kuwabara M, Niwa K, Maharani N, Kato M, Ogino K, Hamada T, Ninomiya H, Higashi Y, Ichida K, Yamamoto K
  • Journal Title: Circ J Volume: 79 Issue: 5 Pages: 1125-1132
  • DOI: 10.1253/circj.CJ-14-1267
  • NAID: 130005066259
  • Peer Reviewed / Open Access
• [Journal Article] Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration. (2015)
  • Author(s): Nakamura Y, Miyaki S, Ishitobi H, Matsuyama S, Nakasa T, Kamei N, Akimoto T, Higashi Y, Ochi M.
  • Journal Title: FEBS Lett. Volume: 589 Pages: 1257-1265
  • DOI: 10.1016/j.febslet.2015.03.031
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Promotion of skeletal muscle regeneration in rat skeletal muscle injury model by local injection of human adipose tissue-derived regenerative cells. (2015)
  • Author(s): Ryo Mori, Naosuke Kamei, Shingo Okawa, Akihiro Nakabayashi, Kazunori Yokota, Yukihito Higashi, Mitsuo Ochi
  • Journal Title: J Tissue Eng Regen Med. Volume: (in press) Pages: 1150-1160
  • DOI: 10.1002/term.1659
  • Peer Reviewed
• [Journal Article] Rho-associated kinases activity is an independent predictor of cardiovascular events in acute coronary syndrome. (2015)
  • Author(s): Kajikawa M, Noma K, Nakashima A, Maruhashi T, Iwamoto Y, Matsumoto T, Iwamoto A, Oda N, Hidaka T, Kihara Y, Aibara Y, Chayama K, Sasaki S, Kato M, Dote K, Goto C, Liao JK, Higashi Y.
  • Journal Title: Hypertension. Volume: 66(4) Pages: 892-899
  • DOI: 10.1161/hypertensionaha.115.05587
  • Peer Reviewed / Open Access
• [Journal Article] Effect of a Low-Intensity Pulsed Ultrasound Device, SX-1001, on Clinical Symptoms in Buerger Disease With Limb Ischemia (2015)
  • Author(s): Higashi Y, Azuma N, Takeishi Y, Minamino T, Kihara Y, Node K, Sata M, Fukumoto Y, Origasa H, Matsuo H, Naritomi H, Fujita M, Shimizu W.
  • Journal Title: Int. Heart J. Volume: 56(6) Issue: 6 Pages: 632-638
  • DOI: 10.1536/ihj.15-191
  • NAID: 130005113045
  • Peer Reviewed / Open Access
• [Journal Article] Reliability of measurement of endothelial function using a semi-automated device across multiple institutions and establishment of normal/reference values. (2015)
  • Author(s): Tomiyama, H
  • Journal Title: Atherosclerosis. Volume: 242 Pages: 433-42
  • DOI: 10.1016/j.atherosclerosis.2015.08.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rho-associated kinase is a predictor of cardiovascular outcomes. (2014)
  • Author(s): Kajikawa M, Noma K, Maruhashi T, Mikami S, Iwamoto Y, Iwamoto A, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Nakashima A, Goto C, Liao JK, Higashi Y.
  • Journal Title: Hypertension. Volume: 64 Pages: 856-64
  • DOI: 10.1161/hypertensionaha.113.02296
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Poor oral health behavior, decreased frequency of tooth brushing, is associated with endothelial dysfunction. (2014)
  • Author(s): Kajikawa M, Maruhashi T, Iwamoto Y, Iwamoto A, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Nakashima A, Goto C, Noma K, Taguchi A, Higashi Y.
  • Journal Title: Circ J. Volume: 78 Pages: 950-954
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Borderline ankle-brachial index value of 0.91 to 0.99 is associated with endothelial dysfunction. (2014)
  • Author(s): Kajikawa M, Maruhashi T, Iwamoto Y, Iwamoto A, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Nakashima A, Goto C, Noma K, Higashi Y.
  • Journal Title: Circ J. Volume: 78 Pages: 1740-1745
  • NAID: 130004926966
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Relationship between nitroglycerine-induced vasodilation and clinical severity of peripheral arterial disease. (2014)
  • Author(s): Maruhashi T, Nakashima A, Matsumoto T, Oda N, Iwamoto Y, Iwamoto A, Kajikawa M, Kihara Y, Chayama K, Goto C, Noma K, Higashi Y.
  • Journal Title: Atherosclerosis. Volume: 235 Pages: 65-70
  • DOI: 10.1016/j.atherosclerosis.2014.04.012
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Oxidative stress and endothelial dysfunction: clinical evidence and therapeutic implications (review). (2014)
  • Author(s): Higashi Y, Maruhashi T, Noma K, Kihara Y.
  • Journal Title: Trends Cardiovasc Med. Volume: 24(4) Pages: 165-169
  • DOI: 10.1016/j.tcm.2013.12.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Do incretins improve endothelial function (review)? (2014)
  • Author(s): Oyama J, Higashi Y, Node K.
  • Journal Title: Cardiovasc Diabetol. Volume: 13 Pages: 21-21
  • DOI: 10.3810/pgm.2013.05.2659
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A single consumption of curry improved postprandial endothelial function in healthy male subjects: a randomized, controlled crossover trial. (2014)
  • Author(s): Nakayama H, Tsuge N, Sawada H, Masamura N, Yamada S, Satomi S, Higashi Y.
  • Journal Title: Nutr J. Volume: 13 Pages: 67-67
  • DOI: 10.1186/1475-2891-13-67
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Autonomic nervous activation triggered during induction of reactive hyperemia exerts a greater influence on the measured reactive hyperemia index by peripheral arterial tonometry than on flow-mediated vasodilatation of the brachial artery in patients with hypertension. (2014)
  • Author(s): Tomiyama H, Yoshida M, Higashi Y, Takase B, Furumoto T, Kario K, Ohya Y, Yamashina A.
  • Journal Title: Hypertens Res. Volume: 37 Pages: 914-918
  • DOI: 10.1038/hr.2014.103
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Circulating endothelial progenitor cells and placental abruption in women with preeclampsia. (2014)
  • Author(s): Sakashita T, Higashi Y, Soga J, Fujiwara H, Kudo Y.
  • Journal Title: Pregnancy Hypertens. Volume: 4 Pages: 203-208
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Critical role of exogenous nitric oxide in ROCK activity in vascular smooth muscle cells. (2014)
  • Author(s): Maruhashi T, Noma K, Fujimura N, Idei, N, Mikami S, Iwamoto Y, Kajikawa M, Matsumoto T, Hidaka T, Goto C, Kihara Y, Chayama K, Liao JK, Higashi Y.
  • Journal Title: PLoS One. Volume: 9
  • DOI: 10.1371/journal.pone.0109017
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Stroma-directed imatinib therapy impairs the tumor-promoting effect of bone marrow-derived mesenchymal stem cells in an orthotopic transplantation model of colon cancer. (2013)
  • Author(s): Shinagawa K
  • Journal Title: Int J Cancer. Volume: 132 Pages: 813-23
  • DOI: 10.1002/ijc.27735
  • Peer Reviewed
• [Journal Article] Flow-mediated vasodilation and anatomical variation of brachial artery (double brachial artery) in healthy subjects and atherosclerotic patients. (2013)
  • Author(s): Fujii Y, Teragawa H, Soga J, Fujimura N, Idei N, Hidaka T, Hata T, Mikami S, Maruhashi T, Iwamoto Y, Kihara Y, Chayama K, Noma K, Nakashima A, Goto C, Higashi Y.
  • Journal Title: Circ J Volume: 77 Pages: 1073-1080
  • Peer Reviewed
• [Journal Article] Impact of aldosterone-producing adenoma on cardiac structures in echocardiography. (2013)
  • Author(s): Hidaka T, Shiwa T, Fujii Y, Nishioka K, Utsunomiya H, Ishibashi K, Mitsuba N, Dohi Y, Oda N, Noma K, Kurisu S, Nakano Y, Yamamoto H, Ishida T, Higashi Y, Kihara Y.
  • Journal Title: J Echocardiogr. Volume: 24 Pages: 185-190
  • Peer Reviewed
• [Journal Article] Mesenchymal Stem Cells Ameliorate Experimental Peritoneal Fibrosis by Suppressing Inflammation and Inhibiting TGF-b1 Signaling. (2013)
  • Author(s): Ueno, T., Nakashima, A., DOI:, S., Kawamoto, T., Honda, K., Yokoyama, Y., DOI:, T., Higashi, Y., Yorioka, N., Kato, Y., Kohno, N., and Masaki, T
  • Journal Title: Kidney Int. Volume: 84(2) Pages: 297-307
  • DOI: 10.1038/ki.2013.81
  • Peer Reviewed
• [Journal Article] Chronic intake of onion extract containing quercetin improved postprandial endothelial dysfunction in healthy men. (2013)
  • Author(s): Nakayama H, Tsuge N, Sawada H, Higashi Y.
  • Journal Title: J Am Coll Nutr. Volume: 32 Pages: 160-164
  • DOI: 10.1080/07315724.2013.797858
  • Peer Reviewed
• [Journal Article] Nitroglycerine-induced Vasodilation for Assessment of Vascular Function: A Comparison with Flow-mediated Vasodilation. (2013)
  • Author(s): Maruhashi T, Soga J, Idei N, Fujimura N, Mikami S, Iwamoto Y, Kajikawa M, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Noma K, Nakashima A, Goto C, Higashi Y.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 33 Pages: 1401-1408
  • DOI: 10.1161/atvbaha.112.300934
  • Peer Reviewed
• [Journal Article] A novel noninvasive and simple method for assessment of endothelial function: enclosed zone flow-mediated vasodilation (ezFMD) using an oscillation amplitude measurement. (2013)
  • Author(s): Naomi Idei, Teiji Ukawa, Masato Kajikawa, Yumiko Iwamoto, Noritaka Fujimura, Tatsuya Maruhashi, Shinsuke Mikami, Takeshi Matsumoto, Yasuki Kihara, Kazuaki Chayama, Kensuke Noma, Ayumu Nakashima, Tsuneo Takayanagi, Haruka Morimoto, Toshio Tsuji, and Yukihito Higashi
  • Journal Title: Atherosclerosis. Volume: 229(2) Pages: 324-330
  • DOI: 10.1016/j.atherosclerosis.2013.05.016
  • Peer Reviewed
• [Journal Article] Autologous bone-marrow mesenchymal stem cell implantation and endothelial function in a rabbit ischemic limb model. (2013)
  • Author(s): Mikami S, Nakashima A, Nakagawa K, Maruhashi T, Iwamoto Y, Kajikawa M, Matsumoto T, Kihara Y, Chayama K, Noma K, Ochi M, Nishimura M, Tsuji K, Kato Y, Goto C, Higashi Y
  • Journal Title: PLoS ONE. Volume: 8(7)
  • DOI: 10.1371/journal.pone.0067739
  • NAID: 120005311939
  • Peer Reviewed
• [Journal Article] Age-dependent decrease in the chondrogenic potential of human bone marrow mesenchymal stem cells expanded with fibroblast growth factor-2. (2013)
  • Author(s): Kanawa M, Igarashi A, Ronald VS, Higashi Y, Kurihara H, Sugiyama M, Saskianti T, Pan H, Kato Y
  • Journal Title: Cytothrapy. Volume: 15(9) Pages: 1062-1072
  • DOI: 10.1016/j.jcyt.2013.03.015
  • Peer Reviewed
• [Journal Article] Resistin-like molecule b in foam cells is involved in atherosclerosis development. (2013)
  • Author(s): Kushiyama A, Sakoda H, Oue N, Okubo M, Nakatsu Y, Ono H, Fukushima T, Kamata H, Nishimura F, Kikuchi T, Fujishiro M, Nishiyama K, Aburatani H, Kushiyama S, Iizuka M, Taki N, Encinas J, Sentani K, Ogonuki N, Ogura A, Kawazu S, Yasui W, Higashi Y, Kurihara H, Katagiri H, Asano T.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 33 Pages: 1986-1992
  • DOI: 10.1161/atvbaha.113.301546
  • Peer Reviewed / Open Access
• [Journal Article] Association between oral health and the risk of lacunar infarction in Japanese adult males and females. (2013)
  • Author(s): Taguchi A, Miki M, Muto A, Kubokawa K, Migita K, Higashi Y, Yoshinari N
  • Journal Title: Gerontology Volume: 59 Pages: 449-506
  • DOI: 10.1159/000353707
  • Peer Reviewed
• [Journal Article] Hyperuricemia is independently associated with endothelial dysfunction in postmenopausal women but not in premenopausal women. (2013)
  • Author(s): Maruhashi T, Nakashima A, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, Kajikawa M, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Goto C, Noma K, Tomiyama H, Takase B, Yamashina A, Higashi Y.
  • Journal Title: BMJ Open Volume: 2013 Nov 8;3(11)
  • DOI: 10.1136/bmjopen-2013-003659
  • Peer Reviewed
• [Journal Article] Relationship between flow-mediated vasodilatation and cardiovascular risk factors in a large community-based study. (2013)
  • Author(s): Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, Kajikawa M, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Noma K, Nakashima A, Goto C, Tomiyama H, Takase B, Yamashina A, Higashi Y.
  • Journal Title: Heart Volume: 99(24) Pages: 1837-1842
  • DOI: 10.1136/heartjnl-2013-304739
  • Peer Reviewed