国立研究開発法人 国立成育医療研究センター National Center for Child Health and Development

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Scholar & Enterprise

Scholar & Enterprise

Center for Regenerative Medicine

Our center is currently conducting researches into the generation of embryonic stem cells (ESCs) as a source for cell-based therapy, which can help replace damaged tissues and organs and restore their function. We are currently developing ESCs-based treatments for severe congenital urea cycle disorders. Our departments aim to elucidate the mechanisms of fertilization and early embryogenesis. We also conduct clinical trials of cell-based therapy using embryonic stem cell (ESC)-based products by studying differentiation in pluripotent stem cells.

Research focus

Successful generation of ESCs for clinical trial

Embryonic stem cells have two distinctive properties of indefinite proliferation and pluripotential differentiation and are a promising unlimited source of healthy cells for patients with intractable childhood diseases for which there is currently no effective therapy. We aim to generate human ESCs in the development of novel therapies for intractable childhood diseases.

ESC-based therapy for the treatment of severe urea cycle disorders

Urea cycle disorders, such as deficiencies of ornithine transcarbamylase and carbamoyl phosphate synthetase I, have a poor prognosis. As an alternative treatment for these disorders, we are developing ESC-based therapy through the manufacture of hepatocytes from human ESCs. We aim to perform initial first-in-human trials after receiving approval from the Ministry of Health, Labour and Welfare of Japan.

Promotion of regenerative medicine using a variety of human stem cells

Adult stem cells also have great potential in regenerative medicine. We are currently investigating the clinical applications of mesenchymal stem cells, which are distributed in the bone marrow, cord blood, umbilical cord, placenta, menstrual blood, and endometrium. We are currently developing possible industrial and clinical applications of these stem cells.

human reproduction

Our work focuses on human fertilization within the human body. Since the sperm and egg cell fuse within the oviduct, the exact process remains in many ways unclear. By collecting data on spermatogenesis, oogenesis, fertilization, and pre-implantation embryogenesis events, our research aims to elucidate the regulatory factors essential for fertilization, in particular the role of the CD9 tetraspan membrane protein.

Members

Leaders

  • Akihiro Umezawa
    Director, Center for Regenerative Medicine
    Director, Department of Cell Engineering
  • Kenji Miyado
    Cheif, Division of Gamete and Reproductive Biology
  • Hidenori Akutsu
    Director, Department of Reproductive Medicine

Bibliography

2019

  1. Cui C, Enosawa S, Matsunari H, Nagashima H, Umezawa A. Natural Flavonol, Myricetin, Enhances the Function and Survival of Cryopreserved Hepatocytes In Vitro and In Vivo. Int J Mol Sci. 20(24):6123, 2019.
  2. Saito K, Kuwahara A, Ishikawa T, Morisaki N, Miyado M, Miyado K, Fukami M, Miyasaka N, Ishihara O, Irahara M, Saito H. Reply: Artificial cycle 'per se' or the specific protocol of endometrial preparation as responsible for obstetric complications of frozen cycle? Hum Reprod. 34(12):2554-2555, 2019.
  3. Sasaki H, Hamatani T, Kamijo S, Iwai M, Kobanawa M, Ogawa S, Miyado K, Tanaka M. Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence. Front Endocrinol (Lausanne). 10:811, 2019.
  4. Muraya K, Kawasaki T, Yamamoto T, Akutsu H. Enhancement of Cellular Adhesion and Proliferation in Human Mesenchymal Stromal Cells by the Direct Addition of Recombinant Collagen I Peptide to the Culture Medium. Biores Open Access. 8(1):210-218, 2019.
  5. Ito C, Akutsu H, Yao R, Yoshida K, Yamatoya K, Mutoh T, Makino T, Aoyama K, Ishikawa H, Kunimoto K, Tsukita S, Noda T, Kikkawa M, Toshimori K. Odf2 haploinsufficiency causes a new type of decapitated and decaudated spermatozoa, Odf2-DDS, in mice. Sci Rep. 9(1):14249, 2019.
  6. Chen LH , Sung TC , Lee HH , Higuchi A , Su HC , Lin KJ , Huang YR , Ling QD , Kumar SS , Alarfaj AA , Munusamy MA , Nasu M , Chen DC , Hsu ST , Chang Y, Lee KF , Wang HC , Umezawa A . Xeno-free and feeder-free culture and differentiation of human embryonic stem cells on recombinant vitronectin-grafted hydrogels. Biomater Sci. 7(10):4345-4362, 2019.
  7. Shindo M, Inui M, Kang W, Tamano M, Tingwei C, Takada S, Hibino T, Yoshida M, Yoshida K, Okada H, Iwamoto T, Miyado K, Kawano N. Deletion of a Seminal Gene Cluster Reinforces a Crucial Role of SVS2 in Male Fertility. Int J Mol Sci. 20(18):4557, 2019.
  8. Gao Y, Ku NJ, Sung TC, Higuchi A, Hung CS, Lee HH, Ling QD, Cheng NC, Umezawa A, Barro L, Burnouf T, Ye Q, Chen H. The effect of human platelet lysate on the differentiation ability of human adipose-derived stem cells cultured on ECM-coated surfaces. J Mater Chem B. 7(45):7110-7119, 2019.
  9. Aoto S, Katagiri S, Wang Y, Pagnamenta AT, Sakamoto-Abutani R, Toyoda M, Umezawa A, Okamura K. Frequent retrotransposition of endogenous genes in ERCC2-deficient cells derived from a patient with xeroderma pigmentosum. Stem Cell Res Ther. 10(1):273, 2019.
  10. Sung TC, Yang JS, Yeh CC, Liu YC, Jiang YP, Lu MW, Ling QD, Kumar SS, Chang Y, Umezawa A, Chen H, Higuchi A. The design of a thermoresponsive surface for the continuous culture of human pluripotent stem cells. Biomaterials. 221:119411, 2019.
  11. Saito K, Kuwahara A, Ishikawa T, Morisaki N, Miyado M, Miyado K, Fukami M, Miyasaka N, Ishihara O, Irahara M, Saito H. Endometrial preparation methods for frozen-thawed embryo transfer are associated with altered risks of hypertensive disorders of pregnancy, placenta accreta, and gestational diabetes mellitus. Hum Reprod. 34(8):1567-1575, 2019.
  12. Sasaki K, Shiba K, Nakamura A, Kawano N, Satouh Y, Yamaguchi H, Morikawa M, Shibata D, Yanase R, Jokura K, Nomura M, Miyado M, Takada S, Ueno H, Nonaka S, Baba T, Ikawa M, Kikkawa M, Miyado K, Inaba K. Publisher Correction: Calaxin is required for cilia-driven determination of vertebrate laterality. Commun Biol. 2(1):254, 2019.
  13. Sasaki K, Shiba K, Nakamura A, Kawano N, Satouh Y, Yamaguchi H, Morikawa M, Shibata D, Yanase R, Jokura K, Nomura M, Miyado M, Takada S, Ueno H, Nonaka S, Baba T, Ikawa M, Kikkawa M, Miyado K, Inaba K. Erratum: Publisher Correction: Calaxin is required for cilia-driven determination of vertebrate laterality. Commun Biol. 2:254, 2019.
  14. Umezawa A, Hasegawa A, Inoue M, Tanuma-Takahashi A, Kajiwara K, Makino H, Chikazawa E, Okamoto A. Amnion-derived cells as a reliable resource for next- generation regenerative medicine. Placenta. 84:50-56, 2019.
  15. Sasaki K, Shiba K, Nakamura A, Kawano N, Satouh Y, Yamaguchi H, Morikawa M, Shibata D, Yanase R, Jokura K, Nomura M, Miyado M, Takada S, Ueno H, Nonaka S, Baba T, Ikawa M, Kikkawa M, Miyado K, Inaba K. Calaxin is required for cilia-driven determination of vertebrate laterality. Commun Biol. 2:226, 2019.
  16. Ogawa S, Yamada M, Nakamura A, Sugawara T, Nakamura A, Miyajima S, Harada Y, Ooka R, Okawa R, Miyauchi J, Tsumura H, Yoshimura Y, Miyado K, Akutsu H, Tanaka M, Umezawa A, Hamatani T. Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis. Stem Cell Reports. 12(6):1366-1379, 2019.
  17. Yazawa T, Imamichi Y, Yuhki KI, Uwada J, Mikami D, Shimada M, Miyamoto K, Kitano T, Takahashi S, Sekiguchi T, Suzuki N, Rafiqul Islam Khan M, Ushikubi F, Umezawa A, Taniguchi T. Cyclooxygenase-2 is acutely induced by CCAAT/enhancer-binding protein β to produce prostaglandin E2 and F following gonadotropin stimulation in Leydig cells. Mol Reprod Dev. 86(7):786-797, 2019.
  18. Miyado M, Kang W, Kawano N, Miyado K. Microexosomes versus exosomes: Shared components but distinct structures. Regen Ther. 11:31-33, 2019.
  19. Yazawa T, Imamichi Y, Sekiguchi T, Miyamoto K, Uwada J, Khan MRI, Suzuki N, Umezawa A, Taniguchi T. Transcriptional Regulation of Ovarian Steroidogenic Genes: Recent Findings Obtained from Stem Cell-Derived Steroidogenic Cells. Biomed Res Int. 2019:8973076, 2019.
  20. Inoue M, Kajiwara K, Yamaguchi A, Kiyono T, Samura O, Akutsu H, Sago H, Okamoto A, Umezawa A. Autonomous trisomic rescue of Down syndrome cells. Lab Invest. 99(6):885-897, 2019.
  21. Ozeki M, Asada R, Saito AM, Hashimoto H, Fujimura T, Kuroda T, Ueno S, Watanabe S, Nosaka S, Miyasaka M, Umezawa A, Matsuoka K, Maekawa T, Yamada Y, Fujino A, Hirakawa S, Furukawa T, Tajiri T, Kinoshita Y, Souzaki R, Fukao T. Efficacy and safety of sirolimus treatment for intractable lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA). Regen Ther . 10:84-91, 2019.
  22. Ogushi K, Hattori A, Suzuki E, Shima H, Izawa M, Yagasaki H, Horikawa R, Uetake K, Umezawa A, Ishii T, Muroya K, Namba N, Tanaka T, Hirano Y, Yamamoto H, Soneda S, Matsubara K, Kagami M, Miyado M, Fukami M. DNA Methylation Status of SHOX-Flanking CpG Islands in Healthy Individuals and Short Stature Patients with Pseudoautosomal Copy Number Variations. Cytogenet Genome Res. 158(2):56-62, 2019.
  23. Iwai M, Hamatani T, Nakamura A, Kawano N, Kanai S, Kang W, Yoshii N, Odawara Y, Yamada M, Miyamoto Y, Saito T, Saito H, Miyado M, Umezawa A, Miyado K, Tanaka M. Membrane protein CD9 is repositioned and released to enhance uterine function. Lab Invest. 99(2):200-209, 2019.

2018

  1. Ito C, Yamatoya K, Yoshida K, Fujimura L, Sugiyama H, Suganami A, Tamura Y, Hatano M, Miyado K, Toshimori K. Deletion of Eqtn in mice reduces male fertility and sperm-egg adhesion. Reproduction. 156(6):579-590, 2018.
  2. Iwai M, Harada Y, Miyabayashi R, Kang W, Nakamura A, Kawano N, Miyamoto Y, Yamada M, Hamatani T, Miyado M, Yoshida K, Saito H, Tanaka M, Umezawa A, Miyado K. Chemotactic behavior of egg mitochondria in response to sperm fusion in mice. Heliyon. 4(11):e00944, 2018.
  3. Seko Y, Iwanami M, Miyamoto-Matsui K, Takita S, Aoi N, Umezawa A, Kato S. The manner of decay of genetically defective EYS gene transcripts in photoreceptor-directed fibroblasts derived from retinitis pigmentosa patients depends on the type of mutation. Stem Cell Res Ther. 9(1):279, 2018.
  4. Iso Y, Usui S, Toyoda M, Spees JL, Umezawa A, Suzuki H. Bone marrow-derived mesenchymal stem cells inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia after arterial injury in rats. Biochem Biophys Rep. 16:79-87, 2018.
  5. Yasuda S, Kusakawa S, Kuroda T, Miura T, Tano K, Takada N, Matsuyama S, Matsuyama A, Nasu M, Umezawa A, Hayakawa T, Tsutsumi H, Sato Y. Tumorigenicity- associated characteristics of human iPS cell lines. PLoS One. 13(10):e0205022, 2018.
  6. Nakamura A, Kawano N, Motomura K, Kuroda A, Sekiguchi K, Miyado M, Kang W, Miyamoto Y, Hanai M, Iwai M, Yamada M, Hamatani T, Saito T, Saito H, Tanaka M, Umezawa A, Miyado K. Degradation of phosphate polymer polyP enhances lactic fermentation in mice. Genes Cells . 223(10):904-914, 2018.
  7. Nishino K, Arai Y, Takasawa K, Toyoda M, Yamazaki-Inoue M, Sugawara T, Akutsu H, Nishimura K, Ohtaka M, Nakanishi M, Umezawa A. Epigenetic-scale comparison of human iPSCs generated by retrovirus, Sendai virus or episomal vectors. Regen Ther. 9:71-78, 2018.
  8. Kang W, Ishida E, Yamatoya K, Nakamura A, Miyado M, Miyamoto Y, Iwai M, Tatsumi K, Saito T, Saito K, Kawano N, Hamatani T, Umezawa A, Miyado K, Saito H. Autophagy-disrupted LC3 abundance leads to death of supporting cells of human oocytes. Biochem Biophys Rep. 15:107-114, 2018.
  9. Sakai T, Naito AT, Kuramoto Y, Ito M, Okada K, Higo T, Nakagawa A, Shibamoto M, Yamaguchi T, Sumida T, Nomura S, Umezawa A, Miyagawa S, Sawa Y, Morita H, Lee JK, Shiojima I, Sakata Y, Komuro I. Phenotypic Screening Using Patient-Derived Induced Pluripotent Stem Cells Identified Pyr3 as a Candidate Compound for the Treatment of Infantile Hypertrophic Cardiomyopathy. Int Heart J. 59(5):1096-1105, 2018.
  10. Yoshida K, Kang W, Nakamura A, Kawano N, Hanai M, Miyado M, Miyamoto Y, Iwai M, Hamatani T, Saito H, Miyado K, Umezawa A. Ubiquitin-activating enzyme E1 inhibitor PYR-41 retards sperm enlargement after fusion to the egg. Reprod Toxicol. 76:71-77, 2018.
  11. Bai F, Li Z, Umezawa A, Terada N, Jin S. Bacterial type III secretion system as a protein delivery tool for a broad range of biomedical applications. Biotechnol Adv. 36(2):482-493, 2018.
  12. Sugawara T, Sasaki K, Akutsu H. Organoids recapitulate organs? Stem Cell Investig. 5:3, 2018.
  13. Matsunari H, Watanabe M, Nakano K, Enosawa S, Umeyama K, Uchikura A, Yashima S, Fukuda T, Klymiuk N, Kurome M, Kessler B, Wuensch A, Zakhartchenko V, Wolf E, Hanazono Y, Nagaya M, Umezawa A, Nakauchi H, Nagashima H. Modeling lethal X-linked genetic disorders in pigs with ensured fertility. Proc Natl Acad Sci U S A. 115(4):708-713, 2018.
  14. Fukuda A, Umezawa A, Akutsu H. Manipulation of Xist Imprinting in Mouse Preimplantation Embryos. Methods Mol Biol. 1861:47-53, 2018.
  15. Ishii T, Yin C, Seko Y, Umezawa A, Kaneda M. Variation in the Phenotype of Photosensitive Cells Produced from Human Fibroblast Cell Lines. J Nippon Med Sch. 85(2):110-116, 2018.
  16. Takasawa K, Arai Y, Yamazaki-Inoue M, Toyoda M, Akutsu H, Umezawa A, Nishino K. DNA hypermethylation enhanced telomerase reverse transcriptase expression in human-induced pluripotent stem cells. Hum Cell. 31(1):78-86, 2018.

2017

  1. Wakui T, Matsumoto T, Matsubara K, Kawasaki T, Yamaguchi H, Akutsu H. Method for evaluation of human induced pluripotent stem cell quality using image analysis based on the biological morphology of cells. J Med Imaging (Bellingham). 4(4):044003, 2017.
  2. Ohno M, Fuchimoto Y, Hsu HC, Higuchi M, Komura M, Yamaoka T, Umezawa A, Enosawa S, Kuroda T. Airway reconstruction using decellularized tracheal allografts in a porcine model. Pediatr Surg Int. 33(10):1065-1071, 2017.
  3. Kuroda T, Yasuda S, Nakashima H, Takada N, Matsuyama S, Kusakawa S, Umezawa A, Matsuyama A, Kawamata S, Sato Y. Identification of a Gene Encoding Slow Skeletal Muscle Troponin T as a Novel Marker for Immortalization of Retinal Pigment Epithelial Cells. Sci Rep. 7(1):8163, 2017.
  4. Kaneda S, Kawada J, Akutsu H, Ichida J, Ikeuchi Y, Fujii T. Compartmentalized embryoid body culture for induction of spatially patterned differentiation. Biomicrofluidics. 11(4):041101, 2017.
  5. Ochiai H, Kishi K, Kubota Y, Oka A, Hirata E, Yabuki H, Iso Y, Suzuki H, Umezawa A. Transplanted mesenchymal stem cells are effective for skin regeneration in acute cutaneous wounds of pigs. Regen Ther. 7:8-16, 2017.
  6. Miyado M, Yoshida K, Miyado K, Katsumi M, Saito K, Nakamura S, Ogata T, Fukami M. Knockout of Murine Mamld1 Impairs Testicular Growth and Daily Sperm Production but Permits Normal Postnatal Androgen Production and Fertility. Int J Mol Sci. 18(6):1300, 2017.
  7. Kajiwara K, Tanemoto T, Wada S, Karibe J, Ihara N, Ikemoto Y, Kawasaki T, Oishi Y, Samura O, Okamura K, Takada S, Akutsu H, Sago H, Okamoto A, Umezawa A. Fetal Therapy Model of Myelomeningocele with Three-Dimensional Skin Using Amniotic Fluid Cell-Derived Induced Pluripotent Stem Cells. Stem Cell Reports. 8(6):1701-1713, 2017.
  8. Yamatoya K, Saito K, Saito T, Kang W, Nakamura A, Miyado M, Kawano N, Miyamoto Y, Umezawa A, Miyado K, Saito H. Birthweights and Down syndrome in neonates that were delivered after frozen-thawed embryo transfer: The 2007-2012 Japan Society of Obstetrics and Gynecology National Registry data in Japan. Reprod Med Biol. 16(2):228-234, 2017.
  9. Ikemoto Y, Takayama Y, Fujii K, Masuda M, Kato C, Hatsuse H, Fujitani K, Nagao K, Kameyama K, Ikehara H, Toyoda M, Umezawa A, Miyashita T. Somatic mosaicism containing double mutations in PTCH1 revealed by generation of induced pluripotent stem cells from nevoid basal cell carcinoma syndrome. J Med Genet. 54(8):579-584, 2017.
  10. Fukami M, Suzuki E, Izumi Y, Torii T, Narumi S, Igarashi M, Miyado M, Katsumi M, Fujisawa Y, Nakabayashi K, Hata K, Umezawa A, Matsubara Y, Yamauchi J, Ogata T. Paradoxical gain-of-function mutant of the G-protein-coupled receptor PROKR2 promotes early puberty. J Cell Mol Med. 21(10):2623-2626, 2017.
  11. Chen YM, Chen LH, Li MP, Li HF, Higuchi A, Kumar SS, Ling QD, Alarfaj AA, Munusamy MA, Chang Y, Benelli G, Murugan K, Umezawa A. Xeno-free culture of human pluripotent stem cells on oligopeptide-grafted hydrogels with various molecular designs. Sci Rep. 7:45146, 2017.
  12. Kojima J, Fukuda A, Taira H, Kawasaki T, Ito H, Kuji N, Isaka K, Umezawa A, Akutsu H. Efficient production of trophoblast lineage cells from human induced pluripotent stem cells. Lab Invest. 97(10):1188-1200, 2017.
  13. Mitani A, Fukuda A, Miyashita T, Umezawa A, Akutsu H. The serine 106 residue within the N-terminal transactivation domain is crucial for Oct4 function in mice. Zygote. 25(2):197-204, 2017.
  14. Miyado K, Kang W, Yamatoya K, Hanai M, Nakamura A, Mori T, Miyado M, Kawano N. Exosomes versus microexosomes: Shared components but distinct functions. J Plant Res. 30(3):479-483, 2017.
  15. Nakasuji T, Ogonuki N, Chiba T, Kato T, Shiozawa K, Yamatoya K, Tanaka H, Kondo T, Miyado K, Miyasaka N, Kubota T, Ogura A, Asahara H. Complementary Critical Functions of Zfy1 and Zfy2 in Mouse Spermatogenesis and Reproduction. PLoS Genet. 13(1):e1006578, 2017.
  16. Saito K, Miyado K, Yamatoya K, Kuwahara A, Inoue E, Miyado M, Fukami M, Ishikawa T, Saito T, Kubota T, Saito H. Increased incidence of post-term delivery and Cesarean section after frozen-thawed embryo transfer during a hormone replacement cycle. J Assist Reprod Genet. 34(4):465-470, 2017.
  17. Uchida H, Machida M, Miura T, Kawasaki T, Okazaki T, Sasaki K, Sakamoto S, Ohuchi N, Kasahara M, Umezawa A, Akutsu H. A xenogeneic-free system generating functional human gut organoids from pluripotent stem cells. JCI Insight. 2(1):e86492, 2017.
  18. Ando Y, Saito M, Machida M, Yoshida-Noro C, Akutsu H, Takahashi M, Toyoda M, Umezawa A. Can Human Embryonic Stem Cell-Derived Stromal Cells Serve a Starting Material for Myoblasts? Stem Cells Int. 2017:7541734, 2017.
  19. Miyado M, Miyado K, Nakamura A, Fukami M, Yamada G, Oda SI. Expression patterns of Fgf8 and Shh in the developing external genitalia of Suncus murinus. Reproduction. 153(2):187-195, 2017.
  20. Liao H, Sato H, Chiba R, Kawai T, Nakabayashi K, Hata K, Akutsu H, Fujiwara S, Nakamura H. Human cytomegalovirus downregulates SLITRK6 expression through IE2. J Neurovirol. 23(1):79-86, 2017.
  21. Seko Y, Azuma N, Yokoi T, Kami D, Ishii R, Nishina S, Toyoda M, Shimokawa H, Umezawa A. Anteroposterior Patterning of Gene Expression in the Human Infant Sclera: Chondrogenic Potential and Wnt Signaling. Curr Eye Res. 42(1):145-154, 2017.

2016

  1. Miyado M, Inui M, Igarashi M, Katoh-Fukui Y, Takasawa K, Hakoda A, Kanno J, Kashimada K, Miyado K, Tamano M, Ogata T, Takada S, Fukami M. The p.R92W variant of NR5A1/Nr5a1 induces testicular development of 46,XX gonads in humans, but not in mice: phenotypic comparison of human patients and mutation-induced mice. Biol Sex Differ. 7:56, 2016.
  2. Ketcham CM, Umezawa A, Zou H, Siegal GP. Laboratory Investigation web focus on China. Lab Invest. 96(11):1144-1146, 2016.
  3. Fukuda A, Mitani A, Miyashita T, Sado T, Umezawa A, Akutsu H. Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice. PLoS Genet. 12(10):e1006375, 2016.
  4. Yazawa T, Imamichi Y, Miyamoto K, Khan MR, Uwada J, Umezawa A, Taniguchi T. Induction of steroidogenic cells from adult stem cells and pluripotent stem cells [Review]. Endocr J. 63(11):943-951, 2016.
  5. Fukuda A, Mitani A, Miyashita T, Kobayashi H, Umezawa A, Akutsu H. Spatiotemporal dynamics of OCT4 protein localization during preimplantation development in mice. Reproduction. 152(5):417-430, 2016.
  6. Araki N, Kawano N, Kang W, Miyado K, Yoshida K, Yoshida M. Seminal vesicle proteins SVS3 and SVS4 facilitate SVS2 effect on sperm capacitation. Reproduction. 152(4):313-321, 2016. doi: 10.1530/REP-15-0551. Epub 2016 Aug 2. PMID: 27486266.
  7. Furuta T, Miyaki S, Ishitobi H, Ogura T, Kato Y, Kamei N, Miyado K, Higashi Y, Ochi M. Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model. Stem Cells Transl Med. 5(12):1620-1630, 2016.
  8. Akutsu H, Nasu M, Morinaga S, Motoyama T, Homma N, Machida M, Yamazaki-Inoue M, Okamura K, Nakabayashi K, Takada S, Nakamura N, Kanzaki S, Hata K, Umezawa A. In vivo maturation of human embryonic stem cell-derived teratoma over time. Regen Ther. 5:31-39, 2016.
  9. Hayakawa T, Harris I, Joung J, Kanai N, Kawamata S, Kellathur S, Koga J, Lin YC, Maruyama Y, McBlane J, Nishimura T, Renner M, Ridgway A, Salmikangas P, Sakamoto N, Sato D, Sato Y, Toda Y, Umezawa A, Werner M, Wicks S. Report of the International Regulatory Forum on Human Cell Therapy and Gene Therapy Products. Biologicals. 44(5):467-479, 2016.
  10. Imamichi Y, Yuhki KI, Orisaka M, Kitano T, Mukai K, Ushikubi F, Taniguchi T, Umezawa A, Miyamoto K, Yazawa T. 11-Ketotestosterone Is a Major Androgen Produced in Human Gonads. J Clin Endocrinol Metab . 101(10):3582-3591, 2016.
  11. Komuta Y, Ishii T, Kaneda M, Ueda Y, Miyamoto K, Toyoda M, Umezawa A, Seko Y. In vitro transdifferentiation of human peripheral blood mononuclear cells to photoreceptor-like cells. Biol Open. 5(6):709-719, 2016.
  12. Nakamura A, Hamaguchi E, Horikawa R, Nishimura Y, Matsubara K, Sano S, Nagasaki K, Matsubara Y, Umezawa A, Tajima T, Ogata T, Kagami M, Okamura K, Fukami M. Complex Genomic Rearrangement Within the GNAS Region Associated With Familial Pseudohypoparathyroidism Type 1b. J Clin Endocrinol Metab. 101(7):2623-2627, 2016.
  13. Okamura K, Sakaguchi H, Sakamoto-Abutani R, Nakanishi M, Nishimura K, Yamazaki-Inoue M, Ohtaka M, Periasamy VS, Alshatwi AA, Higuchi A, Hanaoka K, Nakabayashi K, Takada S, Hata K, Toyoda M, Umezawa A. Distinctive features of single nucleotide alterations in induced pluripotent stem cells with different types of DNA repair deficiency disorders. Sci Rep. 6:26342, 2016.
  14. Fujinaga H, Fujinaga H, Watanabe N, Kato T, Tamano M, Terao M, Takada S, Ito Y, Umezawa A, Kuroda M. Cord blood-derived endothelial colony-forming cell function is disrupted in congenital diaphragmatic hernia. Am J Physiol Lung Cell Mol Physiol. 310(11):L1143-1154, 2016.
  15. Nishino K, Umezawa A. DNA methylation dynamics in human induced pluripotent stem cells. Hum Cell. 29(3):97-100, 2016.
  16. Tateno H, Saito S, Hiemori K, Kiyoi K, Hasehira K, Toyoda M, Onuma Y, Ito Y, Akutsu H, Hirabayashi J. α2-6 sialylation is a marker of the differentiation potential of human mesenchymal stem cells. Glycobiology. 26(12):1328-1337, 2016.
  17. Higasa K, Miyake N, Yoshimura J, Okamura K, Niihori T, Saitsu H, Doi K, Shimizu M, Nakabayashi K, Aoki Y, Tsurusaki Y, Morishita S, Kawaguchi T, Migita O, Nakayama K, Nakashima M, Mitsui J, Narahara M, Hayashi K, Funayama R, Yamaguchi D, Ishiura H, Ko WY, Hata K, Nagashima T, Yamada R, Matsubara Y, Umezawa A, Tsuji S, Matsumoto N, Matsuda F. Human genetic variation database, a reference database of genetic variations in the Japanese population. J Hum Genet. 61(6):547-553, 2016.
  18. Itakura Y, Sasaki N, Kami D, Gojo S, Umezawa A, Toyoda M. N- and O-glycan cell surface protein modifications associated with cellular senescence and human aging. Cell Biosci. 6:14, 2016.
  19. Mizukami T, Iso Y, Sato C, Sasai M, Spees JL, Toyoda M, Umezawa A, Miyazaki A, Suzuki H. Priming with erythropoietin enhances cell survival and angiogenic effect of mesenchymal stem cell implantation in rat limb ischemia. Regen Ther. 4:1-8, 2016.
  20. Nasu M, Takayama S, Umezawa A. Efficiency of Human Epiphyseal Chondrocytes with Differential Replication Numbers for Cellular Therapy Products. Biomed Res Int. 2016:6437658, 2016.
  21. Sumiyoshi N, Ishitobi H, Miyaki S, Miyado K, Adachi N, Ochi M. The role of tetraspanin CD9 in osteoarthritis using three different mouse models. Biomed Res. 37(5):283-291, 2016.
  22. Tone H, Yoshioka S, Akiyama H, Nishimura A, Ichimura M, Nakatani M, Kiyono T, Toyoda M, Watanabe M, Umezawa A. Embryoid Body-Explant Outgrowth Cultivation from Induced Pluripotent Stem Cells in an Automated Closed Platform. Biomed Res Int. 2016:7098987, 2061.
  23. Sivan PP, Syed S, Mok PL, Higuchi A, Murugan K, Alarfaj AA, Munusamy MA, Awang Hamat R, Umezawa A, Kumar S. Stem Cell Therapy for Treatment of Ocular Disorders. Stem Cells Int. 2016:8304879, 2016.
  24. Yokoyama M, Sato M, Umezawa A, Mitani G, Takagaki T, Yokoyama M, Kawake T, Okada E, Kokubo M, Ito N, Takaku Y, Murai K, Matoba R, Akutsu H, Yamato M, Okano T, Mochida J. Assessment of the Safety of Chondrocyte Sheet Implantation for Cartilage Regeneration. Tissue Eng Part C Methods. 22(1):59-68, 2016.
  25. Hashimoto A, Naito AT, Lee JK, Kitazume-Taneike R, Ito M, Yamaguchi T, Nakata R, Sumida T, Okada K, Nakagawa A, Higo T, Kuramoto Y, Sakai T, Tominaga K, Okinaga T, Kogaki S, Ozono K, Miyagawa S, Sawa Y, Sakata Y, Morita H, Umezawa A, Komuro I. Generation of Induced Pluripotent Stem Cells From Patients With Duchenne Muscular Dystrophy and Their Induction to Cardiomyocytes. Int Heart J. 57(1):112-117, 2016.
  26. Kitajima K, Nakajima M, Kanokoda M, Kyba M, Dandapat A, Tolar J, Saito MK, Toyoda M, Umezawa A, Hara T. GSK3β inhibition activates the CDX/HOX pathway and promotes hemogenic endothelial progenitor differentiation from human pluripotent stem cells. Exp Hematol. 44(1):68-74.e1-10, 2016.
  27. Park SJ, Komiyama Y, Suemori H, Umezawa A, Nakai K. OpenTein: a database of digital whole-slide images of stem cell-derived teratomas. Nucleic Acids Res. 44(D1):D1000-1004, 2016.
  28. Sato H, Ishii Y, Yamamoto S, Azuma E, Takahashi Y, Hamashima T, Umezawa A, Mori H, Kuroda S, Endo S, Sasahara M. PDGFR-β Plays a Key Role in the Ectopic Migration of Neuroblasts in Cerebral Stroke. Stem Cells. 34(3):685-98, 2016.

2015

  1. Hayakawa T, Aoi T, Umezawa A, Ozawa K, Sato Y, Sawa Y, Matsuyama A, Yamanaka S, Yamato M. A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from the processing of human embryonic stem cells. Regen Ther. 2:109-122, 2015.
  2. Hayakawa T, Aoi T, Umezawa A, Ozawa K, Sato Y, Sawa Y, Matsuyama A, Yamanaka S, Yamato M. A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from processing of allogeneic human induced pluripotent stem(-Like) cells. Regen Ther. 2:95-108, 2015.
  3. Hayakawa T, Aoi T, Umezawa A, Ozawa K, Sato Y, Sawa Y, Matsuyama A, Yamanaka S, Yamato M. A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from processing of autologous human induced pluripotent stem(-like) cells. Regen Ther. 2:81-94, 2015.
  4. Hayakawa T, Aoi T, Umezawa A, Ozawa K, Sato Y, Sawa Y, Matsuyama A, Yamanaka S, Yamato M. A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from the processing of allogeneic human somatic stem cells. Regen Ther. 2:70-80, 2015.
  5. Hayakawa T, Aoi T, Umezawa A, Ozawa K, Sato Y, Sawa Y, Matsuyama A, Yamanaka S, Yamato M. A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from the processing of autologous human somatic stem cells. Regen Ther. 2:57-69, 2015.
  6. Higuchi A, Kao SH, Ling QD, Chen YM, Li HF, Alarfaj AA, Munusamy MA, Murugan K, Chang SC, Lee HC, Hsu ST, Kumar SS, Umezawa A. Long-term xeno-free culture of human pluripotent stem cells on hydrogels with optimal elasticity. Sci Rep. 5:18136, 2015.
  7. Nakamura A, Miyado K, Yamatoya K, Kawano N, Umezawa A. Breast milk stimulates growth hormone secretion in infant mice, and phosphorus insufficiency disables this ability and causes dwarfism-like symptoms. Regen Ther. 2:49-56, 2015.
  8. Tsumura H, Ito M, Takami M, Arai M, Li XK, Hamatani T, Igarashi A, Takada S, Miyado K, Umezawa A, Ito Y. Conditional deletion of CD98hc inhibits osteoclast development. Biochem Biophys Rep. 5:203-210, 2015.
  9. Miura T, Sugawara T, Fukuda A, Tamoto R, Kawasaki T, Umezawa A, Akutsu H. Generation of primitive neural stem cells from human fibroblasts using a defined set of factors. Biol Open. 4(11):1595-607, 2015.
  10. Ojima T, Shibata E, Saito S, Toyoda M, Nakajima H, Yamazaki-Inoue M, Miyagawa Y, Kiyokawa N, Fujimoto JI, Sato T, Umezawa A. Glycolipid dynamics in generation and differentiation of induced pluripotent stem cells. Sci Rep. 5:14988, 2015.
  11. Fukuda A, Mitani A, Miyashita T, Umezawa A, Akutsu H. Chromatin condensation of Xist genomic loci during oogenesis in mice. Development. 142(23):4049-4055, 2015.
  12. Miyado M, Miyado K, Katsumi M, Saito K, Nakamura A, Shihara D, Ogata T, Fukami M. Parturition failure in mice lacking Mamld1. Sci Rep. 5:14705, 2015.
  13. Okano T, Sawa Y, Barber E, Umezawa A. Regenerative therapy by fusion of medicine and engineering: First-in-human clinical trials with induced pluripotent stem cells and cell sheet technology: A report of the Symposium of Regenerative Medicine for Patients. Regen Ther . 2:2-5, 2015.
  14. Fukuda A, Tanino M, Matoba R, Umezawa A, Akutsu H. Imbalance between the expression dosages of X-chromosome and autosomal genes in mammalian oocytes. Sci Rep. 5:14101, 2015.
  15. Higuchi A , Ling QD , Kumar SS , Chang Y , Alarfaj AA , Munusamy MA , Murugan K , Hsu ST , Umezawa A . Physical cues of cell culture materials lead the direction of differentiation lineages of pluripotent stem cells. J Mater Chem B. 3(41):8032-8058, 2015.
  16. Hayakawa T, Aoi T, Bravery C, Hoogendoorn K, Knezevic I, Koga J, Maeda D, Matsuyama A, McBlane J, Morio T, Petricciani J, Rao M, Ridgway A, Sato D, Sato Y, Stacey G, Sakamoto N, Trouvin JH, Umezawa A, Yamato M, Yano K, Yokote H, Yoshimatsu K, Zorzi-Morre P. Report of the international conference on regulatory endeavors towards the sound development of human cell therapy products. Biologicals. 43(5):283-297, 2015.
  17. Yazawa T, Imamichi Y, Miyamoto K, Khan MR, Uwada J, Umezawa A, Taniguchi T. Regulation of Steroidogenesis, Development, and Cell Differentiation by Steroidogenic Factor-1 and Liver Receptor Homolog-1. Zoolog Sci. 32(4):323-330, 2015.
  18. Okamura K, Toyoda M, Hata K, Nakabayashi K, Umezawa A. Whole-exome sequencing of fibroblast and its iPS cell lines derived from a patient diagnosed with xeroderma pigmentosum. Genom Data. 6:4-6, 2015.
  19. Takeuchi M, Higashino A, Takeuchi K, Hori Y, Koshiba-Takeuchi K, Makino H, Monobe Y, Kishida M, Adachi J, Takeuchi J, Tomonaga T, Umezawa A, Kameoka Y, Akagi K. Correction: Transcriptional Dynamics of Immortalized Human Mesenchymal Stem Cells during Transformation. PLoS One. 10(6):e0131383, 2015.
  20. Nasu M, Takayama S, Umezawa A. Endochondral ossification model system: designed cell fate of human epiphyseal chondrocytes during long-term implantation. J Cell Physiol. 230(6):1376-1388, 2015.
  21. Takeuchi M, Higashino A, Takeuchi K, Hori Y, Koshiba-Takeuchi K, Makino H, Monobe Y, Kishida M, Adachi J, Takeuchi J, Tomonaga T, Umezawa A, Kameoka Y, Akagi K. Transcriptional Dynamics of Immortalized Human Mesenchymal Stem Cells during Transformation. PLoS One. 10(5):e0126562, 2015.
  22. Akutsu H, Machida M, Kanzaki S, Sugawara T, Ohkura T, Nakamura N, Yamazaki- Inoue M, Miura T, Vemuri MC, Rao MS, Miyado K, Umezawa A. Xenogeneic-free defined conditions for derivation and expansion of human embryonic stem cells with mesenchymal stem cells. Regen Ther. 1:18-29, 2015.
  23. Ono C, Yoshida M, Kawano N, Miyado K, Umezawa A. Staphylococcus epidermidis is involved in a mechanism for female reproduction in mice. Regen Ther. 1:11-17, 2015.
  24. Nakamura A, Miyado K, Nasu M, Kono T, Umezawa A. Phosphorus-insufficient maternal milk is associated with ectopic expression of collagen I and female- specific bony changes in infant mouse cartilages. Regen Ther. 1:5-10, 2015.
  25. Watada Y, Yamashita D, Toyoda M, Tsuchiya K, Hida N, Tanimoto A, Ogawa K, Kanzaki S, Umezawa A. Magnetic resonance monitoring of superparamagnetic iron oxide (SPIO)-labeled stem cells transplanted into the inner ear. Neurosci Res. 95:21-26, 2015.
  26. Mizuno H, Akutsu H, Kato K. Ethical acceptability of research on human- animal chimeric embryos: summary of opinions by the Japanese Expert Panel on Bioethics. Life Sci Soc Policy. 11:15, 2015.
  27. Mizutani T, Ishikane S, Kawabe S, Umezawa A, Miyamoto K. Transcriptional regulation of genes related to progesterone production. Endocr J. 62(9):757-763, 2015.
  28. Mizutani T, Kawabe S, Ishikane S, Imamichi Y, Umezawa A, Miyamoto K. Identification of novel steroidogenic factor 1 (SF-1)-target genes and components of the SF-1 nuclear complex. Mol Cell Endocrinol. 408:133-137, 2015.
  29. Araki N, Trencsényi G, Krasznai ZT, Nizsalóczki E, Sakamoto A, Kawano N, Miyado K, Yoshida K, Yoshida M. Seminal vesicle secretion 2 acts as a protectant of sperm sterols and prevents ectopic sperm capacitation in mice. Biol Reprod. 92(1):8, 2015.
  30. Nonaka MI, Zsigmond E, Kudo A, Kawakami H, Yoshida K, Yoshida M, Kawano N, Miyado K, Nonaka M, Wetsel RA. Epididymal C4b-binding protein is processed and degraded during transit through the duct and is not essential for fertility. Immunobiology. 220(4):467-475, 2015.
  31. Higuchi A, Ling QD, Kumar SS, Munusamy MA, Alarfaj AA, Chang Y, Kao SH, Lin KC, Wang HC, Umezawa A. Generation of pluripotent stem cells without the use of genetic material. Lab Invest. 95(1):26-42, 2015. doi: