Neuroregenerative effect of umbilical cord blood stem cells for hypoxia-ischemia in the neonatal mouseat: a proton MRS study

• Project/Area Number: 25860912
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Kochi University
• Principal Investigator: WANG FEIFEI 高知大学, 教育研究部医療学系基礎医学部門, 助教 (10629033)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 脳性麻痺 / 臍帯血幹細胞 / 神経幹細胞 / 1H-MRS / MRS / 虚血再灌流障害

Outline of Final Research Achievements

The aim of this study was to evaluate the effect of umbilical cord blood for a mouse model of neonatal ischemia-reperfusion brain injury using proton magnetic resonance spectroscopy (1H-MRS) . NOD/SCID mice (postnatal day 9) underwent right common carotid artery occlusion with an aneurysm clip. Following hypoxic exposure, reperfusion was achieved by unclamping the artery. T2 hyperintensity abnormalities reflecting tissue edema were observed in the cortex and striatum at 24 hours after injury. 1H-MRS at 1 week after injury showed a significant decrease in n-acetyl aspartate: choline ratio in the injured group compared to the control group.
The umbilical cord blood cells were transplanted intravenously at 3 weeks after injury.The cell transplanted group tended to show an improvement in behavioral tests, but it was not significantly different compared with the control groups.
These results showed that 1H-MRS is valuable for the diagnosis of a mouse model of neonatal brain injury.

Research Products

• [Journal Article] Intra-arterial transplantation of allogeneic mesenchymal stem cells mounts neuroprotective effects in a transient ischemic stroke model in rats: Analyses of therapeutic time window and its mechanisms (2015)
  • Author(s): Toyoshima A , Yasuhara T , Kameda M , Morimoto J , Takeuchi H , Wang F , Sasaki T , Sasada S , Shinko A , Wakamori T , Okazaki M , Kondo A , Agari T , Borlongan CV, Date I
  • Journal Title: PLOS ONE Volume: - Issue: 6 Pages: e0127302-e0127302
  • DOI: 10.1371/journal.pone.0127302
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Syngeneic transplantation of newborn splenocytes in a murine model of neonatal ischemia-reperfusion brain injury. (2014)
  • Author(s): Wang F, Shen Y, Tsuru E, Yamashita T, Baba N, Tsuda M, Maeda N, Sagara Y.
  • Journal Title: J Matern Fetal Neonatal Med. Volume: 17 Issue: 7 Pages: 1-6
  • DOI: 10.3109/14767058.2014.935327
  • Peer Reviewed / Open Access
• [Journal Article] The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson's disease (2013)
  • Author(s): Tayra JT, Kameda M, Yasuhara T, Agari T, Kadota T, Wang F, Kikuchi Y, Liang H, Shinko A, Wakamori T, Vcelar B, Weik R, Date I
  • Journal Title: Brain Research Volume: 1502 Pages: 55-70
  • DOI: 10.1016/j.brainres.2013.01.042
  • NAID: 120005324796
  • Peer Reviewed
• [Journal Article] Mannitol enhances therapeutic effects of intra-arterial transplantation of mesenchymal stem cells into the brain after traumatic brain injury (2013)
  • Author(s): Okuma Y, Wang F, Toyoshima A, Kameda M, Hishikawa T, Tokunaga K, Sugiu K, Liu K, Haruma J, Nishibori M, Yasuhara T, Date I
  • Journal Title: Neurosci Lett Volume: 554 Pages: 156-61
  • DOI: 10.1016/j.neulet.2013.08.058
  • Peer Reviewed
• [Journal Article] Neuroprotective effects of liraglutide for stroke model of rats (2013)
  • Author(s): Sato K, Kameda M, Yasuhara T, Agari T, Baba T, Wang F, Shinko A, Wakamori T, Toyoshima A, Takeuchi H, Sasaki T, Sasada S, Kondo A, Borlongan CV, Matsumae M, Date I
  • Journal Title: Int J Mol Sci Volume: 14 Issue: 11 Pages: 21513-24
  • DOI: 10.3390/ijms141121513
  • Peer Reviewed
• [Presentation] 臍帯血移植による治療メカニズムの解明はどこまで進んだか～脳性麻痺モデルを用いた基礎研究を通して～ (2015)
  • Author(s): 王 飛霏
  • Organizer: 第3回臍帯血による再生医療研究会
  • Place of Presentation: シーサイドホテル芝弥生（東京都港区）
  • Year and Date: 2015-07-26
  • Invited
• [Presentation] 新生仔脳虚血再灌流障害モデルマウスの臍帯血移植療法における内在性神経幹細胞の損傷脳再生機構 (2015)
  • Author(s): 王飛霏、沈淵、山下竜幸、馬場伸育、都留英美、津田雅之、前田長正、相良祐輔
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: 神奈川県（パシフィコ横浜）
  • Year and Date: 2015-03-19 – 2015-03-21
• [Presentation] ヒト臍帯血細胞と骨髄細胞の幹細胞マーカー発現についての比較検討 (2015)
  • Author(s): 飯塚美知郎、都留英美、馬場伸育、王飛霏、津田雅之、常風興平、横田淳子、前田長正、宮村充彦、相良祐輔
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: 神奈川県（パシフィコ横浜）
  • Year and Date: 2015-03-19 – 2015-03-21
• [Presentation] マウスの末梢血細胞からの抗腫瘍エフェクターの誘導およびその抗腫瘍効果の検討 (2014)
  • Author(s): 沈淵、馬場伸育、王飛霏、山下竜幸、都留英美、片岡佐誉、矢生健一、高石公子、黒岩裕美、津田雅之、相良祐輔、前田長正
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 京都府京都市
• [Remarks] 高知大学医学部先端医療学推進センター・脳性麻痺に対するヒト臍帯血幹細胞輸血治療
  • URL: http://www.kochi-ms.ac.jp/~cbsct/about.html
• [Remarks] 臍帯血による再生医療研究会
  • URL: http://www.kochi-ms.ac.jp/~ucbrm/