Placenta-derived mesenchymal stem cell and exosome in placental function

• Project/Area Number: 17K11241
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nagasaki University
• Principal Investigator: MIURA Kiyonori 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00363490)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 胎盤 / 妊娠 / 間葉系幹細胞 / 妊娠高血圧腎症 / microRNA / 母体血漿 / 産科婦人科 / エクソソーム / Preeclampsia / 分子マーカー / 産科婦人科学 / RNA / preeclampsia / 胎盤機能 / mRNA

Outline of Final Research Achievements

We isolated and expanded adequate numbers of cells with characteristic features of mesenchymal stem cells (MSCs) from the chorionic plate (CP-MSCs), chorionic villi (CV-MSCs), and decidua basalis (DB-MSCs) of human term placental tissues. All placenta-derived MSCs expressed pregnancy-associated C14MC microRNA (miRNA) (miR-323-3p). Interestingly, the placenta-specific C19MC miRNAs (miR-518b and miR517a) were clearly expressed in CP-MSCs and CV-MSCs of foetal origin. High-efficiency siRNA transfection was confirmed in twice-passaged CV-MSCs with little toxicity, and microarray analysis was used to screen for miR-518b target genes. Subsequently, we determined the reference values for circulating pregnancy-associated placental miRNAs on C19MC in maternal plasma throughout pregnancy. The reference values for circulating pregnancy-associated placental miRNAs in maternal plasma may contribute to the prediction of a preeclampsia before the onset of disease.

Academic Significance and Societal Importance of the Research Achievements

胎盤由来MSCにおける妊娠関連microRNAと病態形成との詳細な分子機序についてはさらなる研究が必要であるが、胎盤由来MSCを利用することで妊娠関連疾患の分子メカニズムの解明に有用なツールとなりうることが示唆された。そして、母体血漿中の妊娠関連microRNAを定量化することが妊娠高血圧症候群の病態評価につながる可能性が示唆された。本研究の成果は、産科疾患の病態解明ならびに早期診断に貢献すると期待される。

Research Products

• [Journal Article] Cervical Superficially Invasive Squamous Cell Carcinoma With Supraclavicular Lymph Node Metastasis: A Case Report (2020)
  • Author(s): Kawashita Sayaka、Matsuda Katsuya、Matsuwaki Takahiro、Kurohama Hirokazu、Ito Masahiro、Kishikawa Masao、Miura Kiyonori、Nakashima Masahiro
  • Journal Title: International Journal of Gynecological Pathology Volume: 40 Issue: 1 Pages: 78-83
  • DOI: 10.1097/pgp.0000000000000679
  • Peer Reviewed
• [Journal Article] Paediatric-onset haploinsufficiency of A20 associated with a novel and de novo nonsense TNFAIP3 mutation (2020)
  • Author(s): Endo Yushiro、Funakoshi Yasutomo、Koga Tomohiro、Furukawa Kaori、Sasaki Daisuke、Miura Kiyonori、Yanagihara Katsunori、Moriuchi Hiroyuki、Kawakami Atsushi
  • Journal Title: Rheumatology Volume: 59 Issue: 11 Pages: e85-e87
  • DOI: 10.1093/rheumatology/keaa206
  • Peer Reviewed
• [Journal Article] HTLV-1 targets human placental trophoblasts in seropositive pregnant women (2020)
  • Author(s): Tezuka Kenta、Fuchi Naoki、Okuma Kazu、Tsukiyama Takashi、Miura Shoko、Hasegawa Yuri、Nagata Ai、Komatsu Nahoko、Hasegawa Hiroo、Sasaki Daisuke、Sasaki Eita、Mizukami Takuo、Kuramitsu Madoka、Matsuoka Sahoko、Yanagihara Katsunori、Miura Kiyonori、Hamaguchi Isao
  • Journal Title: Journal of Clinical Investigation Volume: 130 Issue: 11 Pages: 6171-6186
  • DOI: 10.1172/jci135525
  • Peer Reviewed / Open Access
• [Journal Article] The Incidence of Dichorionic Diamniotic Twin Pregnancy After Single Blastocyst Embryo Transfer and Zygosity: 8 Years of Single-Center Experience (2020)
  • Author(s): Konno Hiroko、Murakoshi Takeshi、Miura Kiyonori、Masuzaki Hideaki
  • Journal Title: Twin Research and Human Genetics Volume: 23 Issue: 1 Pages: 51-54
  • DOI: 10.1017/thg.2020.5
  • Peer Reviewed
• [Journal Article] Significance of p53-Binding Protein 1 Nuclear Foci in Cervical Squamous Intraepithelial Lesions: Association With High-Risk Human Papillomavirus Infection and P16INK4a Expression (2020)
  • Author(s): Kawashita Sayaka、Matsuda Katsuya、Kondo Hisayoshi、Kitajima Yuriko、Hasegawa Yuri、Shimada Takako、Kitajima Michio、Miura Kiyonori、Nakashima Masahiro、Masuzaki Hideaki
  • Journal Title: Cancer Control Volume: 27 Issue: 1 Pages: 1-8
  • DOI: 10.1177/1073274819901170
  • NAID: 120006988289
  • Peer Reviewed
• [Journal Article] 妊娠初期の見方と所見 (2020)
  • Author(s): 三浦清徳
  • Journal Title: 臨床産科婦人科 Volume: 74 Pages: 14-22
• [Journal Article] Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT (2019)
  • Author(s): Suzumori N, Sekizawa A, Samura O, Yotsumoto J, Sago H,et al
  • Journal Title: Prenatal Diagnosis Volume: 39(2) Issue: 2 Pages: 100-106
  • DOI: 10.1002/pd.5408
  • Peer Reviewed
• [Journal Article] IFPA meeting 2018 workshop report I: Reproduction and placentation among ocean-living species; placental imaging; epigenetics and extracellular vesicles in pregnancy. (2019)
  • Author(s): Acharya G, Bartolomei M, Carter AM, Chamley L, Cotton CF, Hasegawa J, Hasegawa Y, Hayakawa S, Kawaguchi M, Konwar C, Magawa S, Miura K, Nishi H, Salomon C, Sato K, Soejima H, Soma H, Sorensen A, Takahashi H, Tomita T, Whittington CM, Yuan V, O'Tierney-Ginn P.
  • Journal Title: Placenta Volume: 18 Pages: 31201-31203
  • DOI: 10.1016/j.placenta.2019.02.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Malignant transformation from mature cystic teratoma of the ovary (2019)
  • Author(s): Shimada Takako、Higashijima Ai、Fukushima Ai、Komatsu Nahoko、Noguchi Masashi、Ohashi Kazuaki、Hasegawa Yuri、Miura Kiyonori
  • Journal Title: Journal of Obstetrics and Gynaecology Research Volume: 45 Issue: 9 Pages: 1957-1960
  • DOI: 10.1111/jog.14043
  • Peer Reviewed
• [Journal Article] Huge uterine fibroid arising from primary uterine cervical diverticulum: a case report and review of the literatures (2019)
  • Author(s): Noguchi Masashi、Kitajima Michio、Abe Shuhei、Murakami Naoko、Kitajima Yuriko、Miura Kiyonori、Masuzaki Hideaki
  • Journal Title: Journal of Obstetrics and Gynaecology Volume: 39 Issue: 8 Pages: 1186-1187
  • DOI: 10.1080/01443615.2019.1588237
  • Peer Reviewed
• [Journal Article] Comprehensive immune complexome analysis detects disease-specific immune complex antigens in seminal plasma and follicular fluids derived from infertile men and women (2019)
  • Author(s): Murakami Naoko、Kitajima Michio、Ohyama Kaname、Aibara Nozomi、Taniguchi Ken、Wei Mian、Kitajima Yuriko、Miura Kiyonori、Masuzaki Hideaki
  • Journal Title: Clinica Chimica Acta Volume: 495 Pages: 545-551
  • DOI: 10.1016/j.cca.2019.05.031
  • NAID: 120006987696
  • Peer Reviewed / Open Access
• [Journal Article] Impaired early‐phase suppression of glucagon secretion after glucose load is associated with insulin requirement during pregnancy in gestational diabetes (2019)
  • Author(s): Horie Ichiro、Haraguchi Ai、Ito Ayako、Nozaki Aya、Natsuda Shoko、Akazawa Satoru、Mori Yoshitaka、Ando Takao、Higashijima Ai、Hasegawa Yuri、Yoshida Atsushi、Miura Kiyonori、Masuzaki Hideaki、Kawakami Atsushi、Abiru Norio
  • Journal Title: Journal of Diabetes Investigation Volume: 11 Issue: 1 Pages: 232-240
  • DOI: 10.1111/jdi.13096
  • NAID: 120006988318
  • Peer Reviewed
• [Journal Article] 産後の子宮内容物排出異常に対して駆癌血剤が有効であった７例 (2019)
  • Author(s): 高野玲、増﨑雅子、吉田敦、三浦清徳、増﨑英明
  • Journal Title: 産婦人科漢方研究のあゆみ Volume: 36 Pages: 94-98
• [Journal Article] 胎盤限局性モザイク (2019)
  • Author(s): 三浦清徳
  • Journal Title: 三浦清徳 Volume: － Pages: 164-168
• [Journal Article] NIPTで性染色体数的異常は検出できるか? (2019)
  • Author(s): 三浦清徳、三浦生子、増崎英明
  • Journal Title: 臨床婦人科産科 Volume: 73 Pages: 253-257
• [Journal Article] 胎盤とモザイク (2019)
  • Author(s): 三浦清徳
  • Journal Title: 医学のあゆみ Volume: 269 Pages: 775-778
• [Journal Article] 心肺停止し搬送された妊婦に死戦期帝王切開術を施行した一例 (2019)
  • Author(s): 渡邊灯、長谷川ゆり、永田典子、村上直子、東島愛、松本加奈子、北島道夫、三浦清徳、増﨑英明
  • Journal Title: 日本産婦人科・新生児血液学会誌 Volume: 269 Pages: 39-40
• [Journal Article] Development of reference material with assigned value for human T-cell leukemia virus type 1 quantitative PCR in Japan (2018)
  • Author(s): Kuramitsu M、Okuma K、Nakashima M、Sato T、Sasaki D、Hasegawa H、Umeki K、Kubota R、Sasada K、Sobata R、Matsumoto C、Kaneko N、Tezuka K、Matsuoka S、Utsunomiya A、Koh KR、Ogata M、Ishitsuka K、Taki M、Nosaka K、Uchimaru K、Iwanaga M、Sagara Y、Yamano Y、Okayama A、Miura K et al
  • Journal Title: Microbiology and Immunology Volume: 62 Issue: 10 Pages: 673-676
  • DOI: 10.1111/1348-0421.12644
  • NAID: 40021702629
  • Peer Reviewed / Open Access
• [Journal Article] Maternal age-specific risk for trisomy 21 based on the clinical performance of NIPT and empirically derived NIPT age-specific positive and negative predictive values in Japan (2018)
  • Author(s): Yamada Takahiro、Japan NIPT consortium*、Sekizawa Akihiko、Fujii Yosuke、Hirose Tatsuko、Samura Osamu、Suzumori Nobuhiro、Miura Kiyonori、Sawai Hideaki、Hirahara Fumiki、Murotsuki Jun、Kamei Yoshimasa、Sago Haruhiko
  • Journal Title: Journal of Human Genetics Volume: 63 Issue: 10 Pages: 1035-1040
  • DOI: 10.1038/s10038-018-0453-8
  • Peer Reviewed
• [Journal Article] Fetal cell-free DNA fraction in maternal plasma for the prediction of hypertensive disorders of pregnancy (2018)
  • Author(s): Suzumori , Sekizawa A,Yotsumoto J, et al
  • Journal Title: Eur J Obstet Gynecol Reprod Biol Volume: 224 Pages: 165-169
  • DOI: 10.1016/j.ejogrb.2018.03.048
  • Peer Reviewed
• [Journal Article] Reference values for circulating pregnancy-associated microRNAs in maternal plasma and their clinical usefulness in uncomplicated pregnancy and hypertensive disorder of pregnancy (2018)
  • Author(s): Murakami Y, Miura K, Sato S, Higashijima A, Hasegawa Y, Miura S, Yoshiura KI, Masuzaki H
  • Journal Title: Journal of Obstetrics and Gynaecology Research Volume: 印刷中 Issue: 5 Pages: 840-851
  • DOI: 10.1111/jog.13610
  • Peer Reviewed
• [Journal Article] Natural course of HTLV-1 proviral DNA levels in carriers during pregnancy (2018)
  • Author(s): Fuchi N, Miura K, Tsukiyama T, Sasaki D, Ishihara K, Tsuruda K, Hasegawa H, Miura S, Yanagihara K, Masuzaki H
  • Journal Title: Journal of Infectious Diseases Volume: 217 Issue: 9 Pages: 1383-1389
  • DOI: 10.1093/infdis/jiy017
  • Peer Reviewed
• [Journal Article] Decreased cell-free but not exosomal miR-518b in maternal plasma is caused by amniocentesis (2018)
  • Author(s): Miura K, Higashijima A, Hasegawa Y, Miura S, Yoshiura KI, Masuzaki H
  • Journal Title: Clinical and Experimental Obstetrics & Gynecology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Maternal age-specific risk for trisomy 21 based on the clinical performance of NIPT and empirically derived NIPT age-specific positive and negative predictive values in Japan (2018)
  • Author(s): Yamada T, Sekizawa A, Fujii Y, Hirose T, Samura O, Suzumori N, Miura K, Sawai H, Hirahara F, and Sago H
  • Journal Title: Journal of Human Genetics Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Proviral features of human T cell leukemia virus type 1 in carriers with indeterminate western blot analysis results. (2017)
  • Author(s): Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T, Umeki K, Sasaki D, Hasegawa H, Kubota R, Sobata R, Matsumoto C, Kaneko N, Momose H, Araki K, Saito M, Nosaka K, Utsunomiya A, Koh K, Ogata M, Uchimaru K, Iwanaga M, Sagara Y, Yamano Y, et al.
  • Journal Title: J Clin Microbiol. Volume: 55(9) Issue: 9 Pages: 2838-2849
  • DOI: 10.1128/jcm.00659-17
  • Peer Reviewed / Open Access
• [Journal Article] Current status of non-invasive prenatal testing in Japan. (2017)
  • Author(s): Samura O, Sekizawa A, Suzumori N, Sasaki A, Wada S, Hamanoue H, Hirahara F, Sawai H, Nakamura H, Yamada T, Miura K, Masuzaki H, Nakayama S, Okai T, Kamei Y, et al.
  • Journal Title: J Obstet Gynaecol Res Volume: 43 Issue: 8 Pages: 1245-1255
  • DOI: 10.1111/jog.13373
  • Peer Reviewed
• [Journal Article] Fetiform teratoma was a parthenogenetic tumour arising from a mature ovum (2017)
  • Author(s): Miura K, Kurabayashi T, Satoh C, Sasaki K, Ishiguro T, Yoshiura KI and Masuzaki H
  • Journal Title: Journal of Human Genetics Volume: 印刷中 Issue: 9 Pages: 803-808
  • DOI: 10.1038/jhg.2017.45
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 出生前診断-ゲノム医学からゲノム医療へ- (2020)
  • Author(s): 三浦清徳
  • Organizer: 第72回日本産科婦人科学会・学術講演会
  • Invited
• [Presentation] HTLV-1母子感染 (2020)
  • Author(s): 三浦清徳
  • Organizer: 第90回日本感染症学会西日本地方会学術集会・第63回日本感染症学会中日本地方会学術集会・第68回日本化学療法学会西日本支部総会
  • Invited
• [Presentation] 周産期と生殖 (2019)
  • Author(s): 三浦清徳
  • Organizer: 第42回日本母体胎児医学会
  • Invited
• [Presentation] HBV,HCV, HTLV-1 (2019)
  • Author(s): 三浦清徳
  • Organizer: 第71回日本産科婦人科学会学術講演会
  • Invited
• [Presentation] HTLV-1の母子感染抑止プロジェクト (2019)
  • Author(s): 三浦清徳
  • Organizer: 第93回日本感染症学会総会・学術講演会
  • Invited
• [Presentation] 出生前診断の遺伝カウンセリング (2018)
  • Author(s): 三浦清徳
  • Organizer: 第70回日本産科婦人科学会学術講演会
  • Invited
• [Presentation] 遺伝性乳がん卵巣がん症候群について (2018)
  • Author(s): 三浦清徳
  • Organizer: 第14回九州LBC研究会学術集会
  • Invited
• [Presentation] 3.Clinical significances of C19MC and C14MC microRNAs in perinatal management (2018)
  • Author(s): 三浦清徳
  • Organizer: International Federation of Placenta Associations (IFPA)2018
  • Int'l Joint Research
• [Presentation] 生殖医療・出生前診断 (2018)
  • Author(s): 三浦清徳
  • Organizer: 日本人類遺伝学会第63回大会
  • Invited
• [Presentation] 周産期カウンセリングにおける必須知識 (2018)
  • Author(s): 三浦清徳
  • Organizer: 第4回日本産科婦人科遺伝診療学会
  • Invited
• [Presentation] Identification of mesenchymal stem cells derived from human placental tissue (2018)
  • Author(s): Miura K, Fuchi N, Li TS, Masuzaki H
  • Organizer: The 21th International Conference on Prenatal Diagnosis and Therapy
  • Int'l Joint Research
• [Presentation] 出生前診断における遺伝カウンセリング体制 (2017)
  • Author(s): 三浦清徳、増崎英明
  • Organizer: 第3回日本産科婦人科遺伝診療学会
  • Invited
• [Presentation] 母体血を用いた胎児染色体検査で13トリソミー偽陽性であった1例 (2017)
  • Author(s): 三浦清徳、尾崎 守、長谷川ゆり、三浦生子、増崎英明
  • Organizer: 第25回日本胎盤学会学術集会
• [Presentation] ガイドラインや見解で出生前診断はどう変わったか (2017)
  • Author(s): 三浦清徳、増崎英明
  • Organizer: 第53回日本周産期・新生児医学会
  • Invited
• [Presentation] 本邦における超音波検査による胎児診断の現状に関する調査 (2017)
  • Author(s): 三浦清徳、増崎英明
  • Organizer: 第90回日本超音波医学会学術集会
  • Invited
• [Presentation] Decreased cell-free but not exosomal miR-518b in maternal plasma is caused by amniocentesis (2017)
  • Author(s): Miura K, Higashijima A, Miura S, Hasegawa Y, Masuzaki H
  • Organizer: 第69回日本産科婦人科学会学術講演会
• [Book] Fetal Morph Functional Diagnosis. Chapter 22 Gene Disorders and Genetic Counseling (2021)
  • Author(s): Miura S and Miura K
  • Total Pages: 354
  • Publisher: Springer
• [Remarks] 長崎大学産婦人科
  • URL: https://www.med.nagasaki-u.ac.jp/gyneclgy/
• [Remarks] 長崎大学産婦人科ホームページ
  • URL: http://www.med.nagasaki-u.ac.jp/gyneclgy/
• [Remarks] 長崎大学医学部産婦人科ホームページ
  • URL: http://www.med.nagasaki-u.ac.jp/gyneclgy/
• [Remarks] 長崎大学医学部産婦人科
  • URL: http://www.med.nagasaki-u.ac.jp/gyneclgy/