Development of stem cell therapy derived from autologous amniotic fluid cells for cerebral palsy

• Project/Area Number: 15K09724
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Keio University
• Principal Investigator: OCHIAI DAIGO 慶應義塾大学, 医学部(信濃町), 助教 (80348713)
• Co-Investigator(Kenkyū-buntansha): 田中 守 慶應義塾大学, 医学部, 講師 (20207145)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 羊水 / 脳性麻痺 / 幹細胞 / 神経 / 脳傷害 / 胎児

Outline of Final Research Achievements

Hypoxic-ischemic encephalopathy (HIE) remains a major cause of cerebral palsy. However, the efficacy of human amniotic fluid stem cells (hAFS) for HIE, especially in the chronic phase, remains unclear. The aim of this study was to determine the effect of hAFS on the chronic phase of HIE.
hAFS were isolated from AF cells as CD117 + cells. Hypoxia-Ischemia (HI) was induced in mice at postnatal day 9 (P9). Animals intranasally received hAFS or PBS at P19 and were harvested for histological analysis after functional tests at P30. hAFS improved sensorimotor deficits in HIE by brain restoration followed by migration to the lesion. These results suggest that hAFS administration could be a novel treatment for HIE, especially in the chronic phase.

Research Products

• [Journal Article] Human Amniotic Fluid Stem Cells: Therapeutic Potential for Perinatal Patients with Intractable Neurological Disease (2018)
  • Author(s): Ochiai D, Masuda H, Abe Y, Otani T, Fukutake M, Matsumoto T, Miyakoshi K, Tanaka M
  • Journal Title: The Keio Journal of Medicine Volume: 67 Issue: 4 Pages: 57-66
  • DOI: 10.2302/kjm.2017-0019-IR
  • NAID: 130007552319
  • ISSN: 0022-9717, 1880-1293
  • Peer Reviewed
• [Journal Article] Association of Maternal Factors with Perinatal Complications in Pregnancies Complicated with Diabetes: A Single-Center Retrospective Analysis. (2018)
  • Author(s): Endo S, Saisho Y, Miyakoshi K, Ochiai D, Matsumoto T, Kawano Y, Mitsuishi M, Irie J, Tanaka M, Meguro S, Tanaka M, Itoh H.
  • Journal Title: J Clin Med Volume: 7 Issue: 1 Pages: 5-5
  • DOI: 10.3390/jcm7010005
  • Peer Reviewed / Open Access
• [Journal Article] Cover Image, Volume 176A, Number 1, January 2018. (2018)
  • Author(s): Ikenoue S, Miyakoshi K, Ishii T, Sato Y, Otani T, Akiba Y, Kasuga Y, Ochiai D, Matsumoto T, Ichihashi Y, Matsuzaki Y, Tachikawa K, Michigami T, Nishimura G, Ikeda K, Hasegawa T, Tanaka M
  • Journal Title: American journal of medical genetics. Part A Volume: 176 Issue: 1 Pages: 1-1
  • DOI: 10.1002/ajmg.a.38585
  • Peer Reviewed
• [Journal Article] Umbilical cord hemangioma: Sonographic features by HDlive Flow. (2018)
  • Author(s): Akiba Y, Miyakoshi K, Ochiai D, Kawaida M, Matsumoto T, Tanaka M.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol. Volume: 221 Pages: 195-196
  • DOI: 10.1016/j.ejogrb.2017.12.011
  • Peer Reviewed
• [Journal Article] Discordant fetal phenotype of hypophosphatasia in two siblings. (2018)
  • Author(s): Ikenoue S, Miyakoshi K, Ishii T, Sato Y, Otani T, Akiba Y, Kasuga Y, Ochiai D, Matsumoto T, Ichihashi Y, Matsuzaki Y, Tachikawa K, Michigami T, Nishimura G, Ikeda K, Hasegawa T, Tanaka M
  • Journal Title: American journal of medical genetics. Part A Volume: 176 Issue: 1 Pages: 171-174
  • DOI: 10.1002/ajmg.a.38531
  • Peer Reviewed
• [Journal Article] Prenatal sonographic images of left pulmonary artery sling. (2017)
  • Author(s): Ochiai D, Miyakoshi K, Koinuma G, Matsumoto T, Tanaka M.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol. Volume: 211 Pages: 217-218
  • DOI: 10.1016/j.ejogrb.2016.12.026
  • Peer Reviewed
• [Journal Article] Association of common polymorphisms with gestational diabetes mellitus in Japanese women: A case-control study (2017)
  • Author(s): Kasuga, Y. Hata, K. Tajima, A. Ochiai, D. Saisho, Y. Matsumoto, T. Arata, N. Miyakoshi, K. Tanaka, M.
  • Journal Title: Endocrine Journal Volume: 64 Issue: 4 Pages: 463-475
  • DOI: 10.1507/endocrj.EJ16-0431
  • NAID: 130005630406
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prenatal sonographic images of left pulmonary artery sling. (2017)
  • Author(s): Ochiai D, Miyakoshi K, Koinuma G, Matsumoto T, Tanaka M.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol. Volume: 211 Pages: 217-218
  • DOI: 10.1016/j.ejogrb.2015.09.035
  • Peer Reviewed
• [Journal Article] Mid-trimester residual cervical length and the risk of preterm birth in pregnancies after abdominal radical trachelectomy: a retrospective analysis. (2017)
  • Author(s): Kasuga Y, Miyakoshi K, Nishio H, Akiba Y, Otani T, Fukutake M, Ikenoue S, Ochiai D, Matsumoto T, Tanaka K, Minegishi K, Kuji N, Roberts R, Aoki D, Tanaka M.
  • Journal Title: BJOG. Volume: 印刷中 Issue: 11 Pages: 1729-1735
  • DOI: 10.1111/1471-0528.14688
  • Peer Reviewed
• [Journal Article] Atypical HELLP syndrome secondary to uteroplacental insufficiency (2017)
  • Author(s): Ochiai D, Miyakoshi K, Akiba Y, Otani T, Matsumoto T, Tanaka M.
  • Journal Title: Hypertension rsearch in pregnancy Volume: 印刷中
  • NAID: 130006943036
  • Peer Reviewed
• [Journal Article] Pregnancy Outcomes After Abdominal Radical Trachelectomy for Early-Stage Cervical Cancer: A 13-Year Experience in a Single Tertiary-Care Center. (2016)
  • Author(s): Kasuga Y, Nishio H, Miyakoshi K, Sato S, Sugiyama J, Matsumoto T, Tanaka K, Ochiai D, Minegishi K, Hamatani T, Iwata T, Morisada T, Nakamura M, Fujii T, Kuji N, Aoki D, Tanaka M
  • Journal Title: Int J Gynecol Cancer. Volume: 26 Pages: 163-168
  • Peer Reviewed
• [Journal Article] Time-dependent changes in insulin requirement for maternal glycemic control during antenatal corticosteroid therapy in women with gestational diabetes: a retrospective study. (2016)
  • Author(s): Itoh A, Saisho Y, Miyakoshi K, Fukutake M, Kasuga Y, Ochiai D, Matsumoto T, Tanaka M, Itoh H
  • Journal Title: Endocr J. Volume: 63 Pages: 101-104
  • NAID: 130005121489
  • Peer Reviewed
• [Journal Article] Prenatal diagnosis of thrombosed dural sinus malformation with periorbital hemangioma: a case report. (2016)
  • Author(s): Ochiai D, Miyakoshi K, Miwa T, Fukutake M, Kasuga Y, Matsumoto T, Tanaka M
  • Journal Title: Eur J Obstet Gynecol Reprod Biol. Volume: 198 Pages: 157-159
  • Peer Reviewed
• [Presentation] A novel strategy to treat fetal myelomeningocele using human amniotic fluid stem cells (2018)
  • Author(s): Yushi Abe, Daigo Ochiai, Hirotaka Masuda, Toshimitsu Otani, Marie Fukutake, Youhei Akiba, Tadashi Matsumoto, Kei Miyakoshi, Mamoru Tanaka
  • Organizer: Society for Reproductive Investigation
  • Int'l Joint Research
• [Presentation] Human amniotic fluid stem cells have a unique potential to accelerate cutaneous wound healing with less fibrotic scarring like fetal wound healing (2018)
  • Author(s): Yu Sato, Daigo Ochiai, Hirotaka Masuda, Yushi Abe, Toshimitsu Otani, Marie Fukutake, Youhei Akiba, Tadashi Matsumoto, Kei Miyakoshi, Mamoru Tanaka
  • Organizer: Society for Reproductive Investigation
  • Int'l Joint Research
• [Presentation] Human amniotic fluid stem cells :A novel treatment option for neonatal cerebral palsy (2018)
  • Author(s): Toshimitsu Otani, Daigo Ochiai, Marie Fukutake, Yushi Abe, Yu Sato, Youhei Akiba, Tadashi Matsumoto, Hirotaka Masuda, Kei Miyakoshi, Mamoru Tanaka
  • Organizer: Society for Reproductive Investigation
  • Int'l Joint Research
• [Presentation] ヒト羊水幹細胞を用いた脊髄髄膜瘤に対する新規胎児治療法の開発 (2018)
  • Author(s): 阿部雄志，落合大吾，升田博隆，大谷利光，福武麻里絵，秋葉洋平，松本直，宮越敬，田中守
  • Organizer: 日本再生医療学会
• [Presentation] Effects of human amniotic fluid stem cells on cutaneous wound healing in a mouse excisional model (2017)
  • Author(s): Marie Fukutake, Daigo Ochiai, Hirotaka Masuda, Yu Sato, Youhei Akiba, Toshimitsu Otani, Satoru Ikenoue, Yoshifumi Kasuga, Tadashi Matsumoto, Kei Miyakoshi, Mamoru Tanaka, Daisuke Aoki
  • Organizer: Japan Society of Obstetrics and Gynecology
  • Int'l Joint Research
• [Presentation] ヒト羊水幹細胞がマウス皮膚再生に与える影響 － 細胞局所注射ならびに細胞シート貼付における検討 (2017)
  • Author(s): 福武麻里絵, 落合大吾, 佐藤佑, 秋葉洋平, 大谷利光, 池ノ上学, 春日義史, 松本直, 宮越敬, 田中守
  • Organizer: 日本周産期・新生児医学会
• [Presentation] ヒト羊水幹細胞の投与前調整法に関する検討 (2017)
  • Author(s): 阿部雄志，落合大吾，福武麻里絵，大谷利光，升田博隆，秋葉洋平，松本直，宮越敬，田中守
  • Organizer: 臍帯血による再生医療研究会
• [Presentation] ヒト羊水幹細胞の羊水腔内注入によるラット脊髄髄膜瘤の治療効果に関する検討 (2017)
  • Author(s): 落合大吾, 阿部雄志, 大谷利光, 福武麻里絵, 升田博隆, 佐藤佑, 秋葉洋平, 松本直, 宮越敬, 田中守
  • Organizer: 日本胎児治療学会
• [Presentation] The effect of human amniotic fluid stem cells on the cutaneous wound healing (2016)
  • Author(s): Daigo Ochiai, Marie Fukutake, Hirotaka Masuda, Tadashi Matsumoto, Kei Miyakoshi, and Mamoru Tanaka
  • Organizer: 19th Congress of the Federation of Asia and Oceania Perinatal Societies
  • Place of Presentation: 台北（台湾）
  • Year and Date: 2016-12-01
  • Int'l Joint Research
• [Presentation] ヒト羊水幹細胞がマウス皮膚創傷治癒に与える影響 (2016)
  • Author(s): 福武麻里絵、落合大吾、升田博隆、大谷利光、秋葉洋平、春日義史、池ノ上学、松本直、宮越敬、田中守
  • Organizer: 第14回 日本胎児治療学会学術集会
  • Place of Presentation: 聖隷浜松病院（静岡県浜松市）
  • Year and Date: 2016-11-18
• [Presentation] ヒト羊水幹細胞はマウス皮膚創傷治癒を促進する (2016)
  • Author(s): 福武麻里絵、落合大吾、大谷利光、秋葉洋平、春日義史、池ノ上学、松本直、宮越敬、田中守
  • Organizer: 第52回 日本周産期・新生児医学会学術集会
  • Place of Presentation: 富山国際会議場（富山県富山市）
  • Year and Date: 2016-07-16
• [Presentation] Conditioned medium from human amniotic fluid stem cell ameliorates glutamate-induced apoptosis (2016)
  • Author(s): 福武麻里絵、落合大吾、大谷利光、秋葉洋平、春日義史、池ノ上学、松本直、宮越敬、田中守、青木大輔
  • Organizer: 第68回 日本産科婦人科学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2016-04-21
• [Presentation] Conditioned medium from human amniotic fluid mesenchymal stem cell ameliorated glutamate-induced neuronal cell injury (2016)
  • Author(s): 福武麻里絵、落合大吾、升田博隆、大谷利光、秋葉洋平、春日義史、松本直、宮越敬、田中守
  • Organizer: 63rd Society for Reproductive Investigation
  • Place of Presentation: モントリオール（カナダ）
  • Year and Date: 2016-03-16
  • Int'l Joint Research
• [Presentation] 胎児や新生児への自家移植を目指したヒト羊水幹細胞治療ツールの作成 (2015)
  • Author(s): 福武麻里絵、落合大吾、升田博隆、大谷利光、秋葉洋平、春日義史、松本直、宮越敬、田中守
  • Organizer: 第13回 日本胎児治療学会学術集会
  • Place of Presentation: 横浜情報文化センター（神奈川県横浜市）
  • Year and Date: 2015-11-21