Researchers Database

abe tomoyuki

    Center for Development of Advanced Medical Technology,Open Science Laboratory Assistant Professor
Last Updated :2021/10/17

Researcher Information

URL

J-Global ID

Research Interests

  • 移植・再生医療   トランスレーショナルリサーチ   応用動物   再生医学   幹細胞   

Research Areas

  • Life sciences / Zoological sciences

Academic & Professional Experience

  • 2020/04 - Today  自治医科大学先端医療技術開発センター オープンサイエンスラボラトリー専任講師
  • 2017/10 - Today  Jichi Medical University分子病態治療研究センター 再生医学研究部講師
  • 2013/01 - 2017/09  Jichi Medical UniversityDivision of Regenerative Medicine, Center for Molecular MedicineResearch Associate
  • 2011/04 - 2012/12  Jichi Medical UniversitySchool of Medicineポストドクター

Education

  • 2008/04 - 2011/03  Tokyo University of Agriculture and Technology  United Graduate School of Agricultural Science  Department of Biological Production Science
  • 2006/04 - 2008/03  宇都宮大学大学院  農学研究科  生物生産科学専攻 修士課程
  • 2002/04 - 2006/03  Utsunomiya University  Faculty of Agriculture  生物生産科学科

Published Papers

  • Suvd Byambaa, Hideki Uosaki, Hiromasa Hara, Yasumitsu Nagao, Tomoyuki Abe, Hiroaki Shibata, Osamu Nureki, Tsukasa Ohmori, Yutaka Hanazono
    Experimental animals 69 (2) 189 - 198 1341-1357 2020/04 [Refereed][Not invited]
     
    X-linked severe combined immunodeficiency (X-SCID) is an inherited genetic disorder. A majority of X-SCID subjects carries point mutations in the Interleukin-2 receptor gamma chain (IL2RG) gene. In contrast, Il2rg-knockout mice recapitulating X-SCID phenotype lack a large part of Il2rg instead of point mutations. In this study, we generated novel X-SCID mouse strains with small insertion and deletion (InDel) mutations in Il2rg by using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9. To this end, we injected Streptococcus pyogenes Cas9 (SpCas9) mRNA and single guide RNA targeting the exon 2, 3 or 4 of Il2rg into mouse zygotes. In the F0 generation, we obtained 35 pups and 25 out of them were positive for Surveyor assay, and most of mutants displayed dramatic reductions of T and B lymphocytes in the peripheral blood. By amplicon sequencing, 15 out of 31 founder mice were determined as monoallelic mutants with possible minor mosaicisms while 10 mice were mosaic. Finally, we established new strains with 7-nucleotide deletion and 1-nucleotide insertions in the exon 2 and the exons 3 and 4, respectively. Although no IL2RG protein was detected on T cells of exons 3 and 4 mutants, IL2RG protein was unexpectedly detected in the exon 2 mutants. These data indicated that CRISPR/Cas9 targeting Il2rg causes InDel mutations effectively and generates genetically X-SCID mice. Genetic mutations, however, did not necessarily grant phenotypical alteration, which requires an intensive analysis after establishing a strain to confirm their phenotypes.
  • Nawin Chanthra, Tomoyuki Abe, Matthew Miyamoto, Kiyotoshi Sekiguchi, Chulan Kwon, Yutaka Hanazono, Hideki Uosaki
    Scientific reports 10 (1) 4249 - 4249 2020/03 [Refereed][Not invited]
     
    Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) hold great promise for disease modeling and drug discovery. However, PSC-CMs exhibit immature phenotypes in culture, and the lack of maturity limits their broad applications. While physical and functional analyses are generally used to determine the status of cardiomyocyte maturation, they could be time-consuming and often present challenges in comparing maturation-enhancing strategies. Therefore, there is a demand for a method to assess cardiomyocyte maturation rapidly and reproducibly. In this study, we found that Myomesin-2 (Myom2), encoding M-protein, is upregulated postnatally, and based on this, we targeted TagRFP to the Myom2 locus in mouse embryonic stem cells. Myom2-RFP+ PSC-CMs exhibited more mature phenotypes than RFP- cells in morphology, function and transcriptionally, conductive to sarcomere shortening assays. Using this system, we screened extracellular matrices (ECMs) and identified laminin-511/521 as potent enhancers of cardiomyocyte maturation. Together, we developed and characterized a novel fluorescent reporter system for the assessment of cardiomyocyte maturation and identified potent maturation-enhancing ECMs through this simple and rapid assay. This system is expected to facilitate use of PSC-CMs in a variety of scientific and medical investigations.
  • Asuka Hara, Tomoyuki Abe, Atsushi Hirao, Kazuhiro Sanbe, Hiromichi Ayakawa, Borjigin Sarantonglaga, Mio Yamaguchi, Akane Sato, Atchalalt Khurchabilig, Kazuko Ogata, Rika Fukumori, Shoei Sugita, Yoshikazu Nagao
    Journal of Veterinary Medical Science 80 (2) 263 - 271 1347-7439 2018/02 [Refereed][Not invited]
     
    In order to obtain more information on the development of bovine and ovine fetal mammary glands, a series of mammary glands from fetuses of different ages were analyzed. A total of 16 bovine fetuses with curved crown rump lengths ranging from 12 cm (80 days) to 75 cm (240 days) and 15 ovine fetuses ranging from 55 days to 131 days were examined. We used hematoxylin and eosin stain and Oil-Red-O stain to analyze the developmental and morphogenetic processes of mammary glands. In addition, we used immunohistochemical staining to determine the pattern of expression of cytokeratin 18 (CK18) during luminal epithelial differentiation, α-smooth-muscle actin (α-SMA) for myoepithelial differentiation, Ki-67 for cell proliferation, and estrogen receptor α (ERα). Our analyzes showed: (a) The primary mammary duct begin to proliferate in a lengthwise within the teat at 90 days in bovine fetuses and 63 days in ovine fetus (b) luminal epithelial cells and myoepithelial cells appeared from 90 days in bovine fetuses and 63 days in ovine fetus (c) proliferation of epithelial cells appeared to coincide with the development of the primary and secondary ducts and (d) ERα was not found in the fetal mammary gland, but adipocytes showed the presence of ERα. Overall, these results indicate that the sequence of events in the prenatal development of the mammary gland of sheep is similar to that of cattle.
  • Naoki Osada, Jiro Kikuchi, Takashi Umehara, Shin Sato, Masashi Urabe, Tomoyuki Abe, Nakanobu Hayashi, Masahiko Sugitani, Yutaka Hanazono, Yusuke Furukawa
    Oncotarget 9 (5) 6450 - 6462 1949-2553 2018 [Refereed][Not invited]
     
    Human induced pluripotent stem cells (hiPSCs) are creating great expectations for regenerative medicine. However, safety strategies must be put in place to guard against teratoma formation after transplantation of hiPSC-derived cells into patients. Recent studies indicate that epigenetic regulators act at the initial step of tumorigenesis. Using gain-of-function and loss-of-function approaches, we show here that the expression and function of lysine-specific demethylase 1 (LSD1) are tightly regulated in hiPSCs, and their deregulation underlies the development of teratomas. Consistent with these results, we demonstrate that an LSD1 inhibitor, S2157, prevented teratoma formation from hiPSCs transplanted into immunodeficient mice. This novel action of LSD1 and the effects of its inhibition potentially allow for the development of new clinical applications and therapeutic strategies using hiPSCs.
  • Hiromasa Hara, Hiroaki Shibata, Kazuaki Nakano, Tomoyuki Abe, Hideki Uosaki, Takahiro Ohnuki, Shuji Hishikawa, Satoshi Kunita, Masahito Watanabe, Osamu Nureki, Hiroshi Nagashima, Yutaka Hanazono
    Experimental Animals 67 (2) 139 - 146 1341-1357 2018 [Refereed][Not invited]
     
    Pigs with X-linked severe combined immunodeficiency (X-SCID) caused by a mutation of the interleukin-2 receptor gamma chain gene (IL2RG) are of value for a wide range of studies. However, they do not survive longer than 8 weeks because of their susceptibility to infections. To allow longer survival of X-SCID pigs, the animals must be born and reared under germ-free conditions. Here, we established an efficient system for piglet derivation by hysterectomy and used it to obtain and maintain a germ-free X-SCID pig. In four trials using pregnant wild-type pigs, 66% of piglets after hysterectomy started spontaneous breathing (range of 20–100% per litter). The resuscitation rate was found to negatively correlate with elapsed time from the uterus excision to piglet derivation (r=−0.97, P< 0.05). Therefore, it is critical to deliver piglets within 5 min to achieve a high resuscitation rate (82% estimated from regression analysis). In a fifth trial with an IL2RG+/− pig, four piglets were delivered within 4.2 min of uterus excision and three were alive (75%). One of the live born piglets was genotypically and phenotypically determined to be X-SCID and was reared for 12 weeks. The X-SCID piglet was free from both bacteria and fungi at all time points tested by microbial culture and grew without any abnormal signs or symptoms. This study showed successful production and rearing of germ-free pigs, enabling experiments involving long-term follow-up of X-SCID pigs.
  • Tomoyuki Abe, Yoshikazu Matsuoka, Yoshikazu Nagao, Yoshiaki Sonoda, Yutaka Hanazono
    INTERNATIONAL JOURNAL OF HEMATOLOGY 106 (5) 631 - 637 0925-5710 2017/11 [Refereed][Not invited]
     
    We and others have reported that human hematopoietic stem cells (HSCs) are also present in the CD34-negative (CD34(-)) fraction of human cord blood (CB). Here, we examined the hematopoietic engraftment potential of 13 or 18 lineage-negative (13Lin(-) or 18Lin(-)) CD34(+/-) cells from human CB in mice and sheep. Both 13Lin(-) and 18Lin(-) CD34(+) cells efficiently engrafted in mice irrespective of transplantation route, be it by tail-vein injection (TVI) or by intra-bone marrow injection (IBMI). These cells also engrafted in sheep after in utero fetal intra-hepatic injection (IHI). In contrast, neither 13Lin(-) nor 18Lin(-) CD34(-) cells engrafted in either mice or sheep when transplanted by regular routes (i.e., TVI and fetal IHI, respectively), although both 13Lin(-) and 18Lin(-) CD34(-) cells engrafted in mice when transplanted by IBMI and exhibited multilineage reconstitution ability. Thus, the homing ability of CD34(-) HSCs is significantly more limited than that of CD34(+) HSCs. As for 18Lin(-), CD34(-) HSCs are characterized by low expression of the tetraspanin CD9, which promotes homing, and high expression of the peptidase CD26, which inhibits homing. This unique expression pattern homing-related molecules on CD34(-) HSCs could thus explain in part their reduced ability to home to the BM niche.
  • Abe T, Kono S, Ohnuki T, Hishikawa S, Kunita S, Hanazono Y
    Experimental Animals 2016/10 [Refereed][Not invited]
  • Tomoyuki Abe, Yutaka Hanazono, Yoshikazu Nagao
    EXPERIMENTAL ANIMALS 63 (4) 475 - 481 1341-1357 2014/10 [Refereed][Not invited]
     
    Xenograft models of human hematopoiesis are essential to the study of the engraftment and proliferative potential of human hematopoietic stem cells (HSCs) in vivo. Immunodeficient mice and fetal sheep are often used as xenogeneic recipients because they are immunologically naive. In this study, we transplanted human HSCs into fetal sheep and assessed the long-term engraftment of transplanted human HSCs after birth. Fourteen sheep were used in this study. In 4 fetal sheep, HSCs were transduced with homeo-box B4 (HOXB4) gene before transplantation, which promoted the expansion of HSCs. Another 4 fetal sheep were subjected to non-myeloablative conditioning with busulfan. Seven of these 8 sheep showed successful engraftnnent of human HSCs (1-3% of colonyforming units) as assessed after the birth of fetal sheep (5 months post-transplantation), although HOXB4-transduced HSCs showed sustained engraftment for up to 40 months. Intact HSCs were transplanted into six non-conditioned fetal sheep, and human colony-forming units were not detected in the sheep after birth. These results suggest that, as compared with mouse models, where the short lifespan of mice limits long-term follow-up of HSC engraftment, the fetal sheep model provides a unique perspective for evaluating long-term engraftment and proliferation of human HSCs.
  • Yoshihisa Mizukami, Tomoyuki Abe, Hiroaki Shibata, Yukitoshi Makimura, Shuh-hei Fujishiro, Kimihide Yanase, Shuji Hishikawa, Eiji Kobayashi, Yutaka Hanazono
    PLOS ONE 9 (6) e98319  1932-6203 2014/06 [Refereed][Not invited]
     
    Recent studies have revealed negligible immunogenicity of induced pluripotent stem (iPS) cells in syngeneic mice and in autologous monkeys. Therefore, human iPS cells would not elicit immune responses in the autologous setting. However, given that human leukocyte antigen (HLA)-matched allogeneic iPS cells would likely be used for medical applications, a more faithful model system is needed to reflect HLA-matched allogeneic settings. Here we examined whether iPS cells induce immune responses in the swine leukocyte antigen (SLA)-matched setting. iPS cells were generated from the SLA-defined C1 strain of Clawn miniature swine, which were confirmed to develop teratomas in mice, and transplanted into the testes (n = 4) and ovary (n = 1) of C1 pigs. No teratomas were found in pigs on 47 to 125 days after transplantation. A Mixed lymphocyte reaction revealed that T-cell responses to the transplanted MHC-matched (C1) iPS cells were significantly lower compared to allogeneic cells. The humoral immune responses were also attenuated in the C1-to-C1 setting. More importantly, even MHC-matched iPS cells were susceptible to innate immunity, NK cells and serum complement. iPS cells lacked the expression of SLA class I and sialic acids. The in vitro cytotoxic assay showed that C1 iPS cells were targeted by NK cells and serum complement of C1. In vivo, the C1 iPS cells developed larger teratomas in NK-deficient NOG (T-B-NK-) mice (n = 10) than in NK-competent NOD/SCID (T-B-NK+) mice (n = 8) (p<0.01). In addition, C1 iPS cell failed to form teratomas after incubation with the porcine complement-active serum. Taken together, MHC-matched iPS cells can attenuate cellular and humoral immune responses, but still susceptible to innate immunity in pigs.
  • Shuh-hei Fujishiro, Kazuaki Nakano, Yoshihisa Mizukami, Takuya Azami, Yoshikazu Arai, Hitomi Matsunari, Rikiya Ishino, Takashi Nishimura, Masahito Watanabe, Tomoyuki Abe, Yutaka Furukawa, Kazuhiro Umeyama, Shinya Yamanaka, Masatsugu Ema, Hiroshi Nagashima, Yutaka Hanazono
    STEM CELLS AND DEVELOPMENT 22 (3) 473 - 482 1547-3287 2013/02 [Refereed][Not invited]
     
    In pluripotent stem cells (PSCs), there are 2 types: naive and primed. Only the naive type has the capacity for producing chimeric offspring. Mouse PSCs are naive, but human PSCs are in the primed state. Previously reported porcine PSCs appear in the primed state. In this study, putative naive porcine-induced pluripotent stem cells (iPSCs) were generated. Porcine embryonic fibroblasts were transduced with retroviral vectors expressing Yamanaka's 4 genes. Emergent colonies were propagated in the presence of porcine leukemia inhibitory factor (pLIF) and forskolin. The cells expressed pluripotency markers and formed embryoid bodies, which gave rise to cell types from all 3 embryonic germ layers. The naive state of the cells was demonstrated by pLIF dependency, 2 active X chromosomes (when female), absent MHC class I expression, and characteristic gene expression profiles. The porcine iPSCs contributed to the in vitro embryonic development (11/24, 45.8%) as assessed by fluorescent markers. They also contributed to the in utero fetal development (11/71, 15.5% at day 23; 1/13, 7.7% at day 65). This is the first demonstration of macroscopic fluorescent chimeras derived from naive-like porcine PSCs, although adult chimeras remain to be produced.
  • Tomoyuki Abe, Shigeo Masuda, Yujiro Tanaka, Suguru Nitta, Yoshihiro Kitano, Satoshi Hayashi, Yutaka Hanazono, Yoshikazu Nagao
    EXPERIMENTAL HEMATOLOGY 40 (6) 436 - 444 0301-472X 2012/06 [Refereed][Not invited]
     
    In utero transplantation (IUT) of human hematopoietic stem cells has been conducted in sheep, which are used as large animal models of human hematopoietic reconstitution and models for clinical IUT; however, the levels of engraftment have generally been low. Busulfan (BU), a myeloablative agent, is often administered to patients before hematopoietic stem cells transplantation to improve the engraftment. In this study, hematopoietic activity was evaluated in adult sheep after administering BU at different doses. Next, pregnant ewes were administered BU, and dams as well as their fetuses were evaluated, as BU readily crosses the sheep placenta. Then, the BU dose with the desired outcomes was selected and administered to pregnant ewes at 2 or 6 days before performing JUT using human cord blood CD34(+) cells. The engraftment was evaluated in recipients that underwent JUT in the presence or absence of BU. As a result, hematopoietic activity was safely and transiently suppressed in adult sheep treated with 5 to 7.5 mg/kg BU. BU crossed the sheep placenta, and fetal sheep were indeed conditioned by administering 3 mg/kg BU to pregnant ewes. Engraftment of human CD34(+) cells in fetal recipients was enhanced when IUT was carried out 6 days post-BU. Up to 3.3% engraftment levels (in terms of bone marrow colony-forming units) were achieved with the JUT of 0.72 to 2.4 million CD34(+) cells when BU was used. BU can be administered to pregnant ewes to effectively condition the fetal recipient for IUT with enhanced engraftment of donor cells. (C) 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
  • Shigeo Masuda, Satoshi Hayashi, Naohide Ageyama, Hiroaki Shibata, Tomoyuki Abe, Yoshikazu Nagao, Yutaka Hanazono
    Transplantation 92 (2) e5-6; author reply e6-7 - 6; author reply e6 0041-1337 2011/07 [Refereed][Not invited]
  • Tomoyuki Abe, Shigeo Masuda, Hiroshi Ban, Satoshi Hayashi, Yasuji Ueda, Makoto Inoue, Mamoru Hasegawa, Yoshikazu Nagao, Yutaka Hanazono
    EXPERIMENTAL HEMATOLOGY 39 (1) 47 - 54 0301-472X 2011/01 [Refereed][Not invited]
     
    Objective The homeobox B4 (HoxB4) gene promotes expansion of hematopoietic stem cells (HSCs) However, frequent development of leukemia in large animals duo to retrovirally transduced HoxB4 gene has been reported To prevent tumorigenesis, we developed a nonintegrating and nonreplicating Sendai virus vector that did not contain the phosphoprotein gene (SeV/Delta P), which enabled clearance of the vector and transgene shortly after transduction We tested the SeV/Delta P vector expressing the HoxB4 gene (SeV/Delta P/HoxB4) for the ex vivo expansion of human cord blood CD34(+) cells (HSCs) using a sheep in utero transplantation assay Materials and Methods Human HSCs were ex vivo expanded by transduction with SeV/Delta P/HoxB4 vector and transplanted into the abdominal cavity of fetal sheep The. engraftment of human HSCs in the lambs was quantitatively evaluated by hematopoietic colony forming unit assays Results After transplantation, the HoxB4-transduced HSCs contributed to longer period (up to 20 months) repopulation in sheep, and human hematopoietic progenitors were detected more frequently in the bone marrow of the HoxB4 group as compared with the control untreated group (p < 0 05) The expansion of human HSCs with the SeV/Delta P/HoxB4 vector was comparable with previously reported retroviral vectors expressing HoxB4 The SeV/Delta P/HoxB4 vector and the transgene were cleared from the recipient sheep and leukemia was not detected at 20 months post transplantation Conclusions The SeV/Delta P vector would be suitable for transient expression of HoxB4 in human CD34(+) cells In addition, the SeV/Delta P vector is free of concern about transgene-related and insertional leukemogenesis and should be safer than retroviral vectors (C) 2011 ISFH Society for Hematology and Stem Cells Published by Elsevier Inc
  • Yujiro Tanaka, Shigeo Masuda, Tomoyuki Abe, Satoshi Hayashi, Yoshihiro Kitano, Yoshikazu Nagao, Yutaka Hanazono
    TRANSPLANTATION 90 (4) 462 - 463 0041-1337 2010/08 [Refereed][Not invited]
  • Yoshikazu Nagao, Tomoyuki Abe, Hideaki Hasegawa, Yujiro Tanaka, Kyoko Sasaki, Yoshihiro Kitano, Satoshi Hayashi, Yutaka Hanazono
    CLONING AND STEM CELLS 11 (2) 281 - 285 1536-2302 2009/06 [Refereed][Not invited]
     
    In the present study, we investigated the suitability of two methods for the transplantation of cells into ovine fetuses. The first method was an ultrasound-guided cell injection via the uterine wall. The second involved hysterotomic cell injection with an incision in the uterine wall exposing the amnion. Monkey embryonic stem (ES) cell-derived hematopoietic cells were used as donor cells. After transplantation, the abortion rate associated with the hysterotomic injection method was significantly higher than that of the ultrasound-guided injection method (8/13 versus 4/24; P < 0.01). The fetuses were delivered to examine the engraftment of transplanted monkey hematopoietic cells. Monkey cells were detected in one of the five animals (20%) in the hysterotomic injection group, and 14 of 20 animals (70%, P < 0.05) in the ultrasound-guided injection group. Therefore, the ultrasound-guided method was effectively shown to be minimally invasive for in utero transplantation and can produce a higher rate of engraftment for transplanted cells.
  • Yujiro Tanaka, Shinichiro Nakamura, Hiroaki Shibata, Yukiko Kishi, Tamako Ikeda, Shigeo Masuda, Kyoko Sasaki, Tomoyuki Abe, Satoshi Hayashi, Yoshihiro Kitano, Yoshikazu Nagao, Yutaka Hanazono
    STEM CELLS AND DEVELOPMENT 17 (2) 367 - 381 1547-3287 2008/04 [Refereed][Not invited]
     
    Because embryonic stem (ES) cells are able to proliferate indefinitely and differentiate into any type of cell, they have the potential for providing an inexhaustible supply of transplantable cells or tissues. However, methods for the in vitro differentiation of human ES cells are still quite limited. One possible strategy would be to generate differentiated cells in vivo. In view of future clinical application, we investigated the possibility of using xenogeneic large animals for this purpose. We transplanted nonhuman primate cynomolgus ES cells into fetal sheep at 43-67 gestational days ( full term 147 days, n = 15). After birth, cynomolgus tissues, which were mature teratomas, had been engrafted in sheep when more than 1 X 10(6) ES cells were transplanted at < 50 gestational days. Despite the sustained engraftment, both cellular and humoral immune responses against the ES cells were detected, and additional transplantation was not successful in the animals. At 2 weeks post-transplantation, the ES cell progeny proliferated when transplanted at 48 ( < 50) gestational days, whereas they were cleared away when transplanted at 60 ( < 50) gestational days. These results support the rapid development of the xenogeneic immunological barrier in fetal sheep after 50 gestational days. Notably, a large number of Foxp3(+) regulatory T cells were present around the ES cell progeny, but macrophages were absent when the transplant was conducted at < 50 gestational days, implying that regulatory T cells and premature innate immunity might have contributed to the sustained engraftment. In conclusion, long-term macroscopic engraftment of primate ES cells in sheep is feasible despite the xenogeneic immunological barrier.

MISC

  • ヒトiPS細胞由来造血幹細胞の作成を目指して
    阿部 朋行, 花園 豊  Organ Biology  27-  (2)  167  -172  2020/07  [Not refereed][Not invited]
  • 塩基編集による血友病B患者由来iPSCの遺伝子修復
    平本 貴史, 阿部 朋行, 早川 盛禎, 鴨下 信彦, 稲葉 浩, 柏倉 裕志, 冨樫 朋貴, 西増 弘志, 花園 豊, 濡木 理, 大森 司  日本血栓止血学会誌  31-  (2)  220  -220  2020/05  [Not refereed][Not invited]
  • 阿部 朋行, 柴田 宏昭, 魚崎 英毅, 原 弘真, ボラジギン・サラントラガ, 長尾 慶和, 花園 豊  Organ Biology  26-  (3)  87  -87  2019/10  [Not refereed][Not invited]
  • 原 弘真, 伊藤 拓哉, 菱川 修司, 中野 和明, 阿部 朋行, 柴田 宏昭, 魚崎 英毅, 渡邊 將人, 國田 智, 長嶋 比呂志, 花園 豊  Organ Biology  26-  (3)  89  -89  2019/10  [Not refereed][Not invited]
  • 原 弘真, 菱川 修司, 伊藤 拓哉, 阿部 朋行, 柴田 宏昭, 魚崎 英毅, 國田 智, 花園 豊  Organ Biology  26-  (3)  121  -121  2019/10  [Not refereed][Not invited]
  • 和食の健康維持・増進効果の機序解明を目指した研究
    原 弘真, 永山 学, 須田 亙, 柴田 宏昭, 菱川 修司, 國田 智, 阿部 朋行, 魚崎 英毅, 新 幸二, 本田 賢也, 花園 豊  自治医科大学紀要  41-  92  -92  2019/03  [Not refereed][Not invited]
  • 阿部朋行, 長尾慶和, 花園豊  Journal of Reproduction and Development  64-  (Suppl.)  j46  -j46  2018/09  [Not refereed][Not invited]
  • 原弘真, 永山学, 永山学, 永山学, 須田亙, 柴田宏昭, 柴田宏昭, 大貫貴広, 菱川修司, 國田智, 阿部朋行, 阿部朋行, 魚崎英毅, 魚崎英毅, 新幸二, 本田賢也, 本田賢也, 花園豊, 花園豊  日本実験動物学会総会講演要旨集  65th-  157  2018/04  [Not refereed][Not invited]
  • 原 弘真, 柴田 宏昭, 中野 和明, 阿部 朋行, 魚崎 英毅, 大貫 貴広, 菱川 修司, 國田 智, 渡邊 將人, 濡木 理, 長嶋 比呂志, 花園 豊  Experimental Animals  67-  (2)  139  -146  2018/04  [Not refereed][Not invited]
     
    我々は近年、インターロイキン2受容体γ鎖を欠損するX連鎖重症複合免疫不全症(X-SCID)ブタを作出した。しかし、X-SCIDブタは免疫不全であるが故に生後8週間以内に感染死してしまうため、より長期的な試験に用いる際には無菌的に飼育する必要がある。本研究では、まず子宮切断術による効率的な無菌ブタ作出技術の確立を行い、次に当該技術により作出したSCIDブタの無菌的飼育を試みた。はじめに、4頭の野生型妊娠ブタ(妊娠112日)から、子宮切断術により胎仔を摘出したところ、66%(21/32;20-100%)の摘出胎仔が蘇生した。子宮切断から胎仔摘出完了までの時間と蘇生率の間に強い負の相関(r=-0.97、P<0.05)が認められ、5分以内に胎仔を摘出することで蘇生率を82%程度に改善されることが示された。次に、X-SCIDキャリアメスと野生型オスを交配して得た妊娠ブタの子宮切断術を実施したところ、4.2分以内に4頭すべての胎仔を摘出できた。4頭中3頭が蘇生し(蘇生率75%)、内1頭がX-SCIDだった。このX-SCIDブタは、細菌および真菌を検出できる培養検査により無菌状態であることが確認され、摘出後12週間にわたって無菌状態で飼育することに成功した。無菌状態で維持している間、X-SCIDブタに異常な徴候は認められなかった。以上の結果から、子宮切断術を5分以内に完了することで、無菌ブタを効率的に作出できることが明らかとなった。また、X-SCIDブタを無菌的に飼育することで長期にわたる試験にも利用できることが示された。(著者抄録)
  • 阿部朋行, 阿部朋行, 柴田宏昭, 原弘真, 魚崎英毅, 魚崎英毅, 大貫貴広, 竹内絢香, 原明日香, SARENTONGLAGA Borjigin, 長尾慶和, 花園豊, 花園豊, 花園豊  日本異種移植研究会プログラム・抄録集  20th-  41  2018  [Not refereed][Not invited]
  • 長尾恭光, 冨永薫, 坂下英司, 阿部朋行, 秋本千鶴, 花園豊, 遠藤仁司  日本生化学会大会(Web)  2017年度-  [3P  -0857]  2017/12  [Not refereed][Not invited]
  • Suvd Byambaa, Hideki Uosaki, Hiromasa Hara, Tomoyuki Abe, Yasumitsu Nagao, Osamu Nureki, Tsukasa Ohmori, Yutaka Hanazono  MOLECULAR THERAPY  25-  (5)  93  -93  2017/05  [Not refereed][Not invited]
  • 阿部朋行, 阿部朋行, 柴田宏昭, 魚崎英毅, 原弘真, 大貫貴広, スブド ビャンバー, ナーウィン ジャントラー, ボラジギン サラントラガ, 福森理加, 長尾慶和, 花園豊, 花園豊, 花園豊  日本実験動物学会総会講演要旨集  64th-  270  2017/04  [Not refereed][Not invited]
  • 原弘真, 柴田宏昭, 中野和明, 阿部朋行, 阿部朋行, 魚崎英毅, 大貫貴広, スブド ビャンバー, ナーウィン ジャントラー, 菱川修司, 國田智, 長嶋比呂志, 濡木理, 花園豊, 花園豊  日本実験動物学会総会講演要旨集  64th-  171  2017/04  [Not refereed][Not invited]
  • 阿部朋行, 阿部朋行, 柴田宏昭, 魚崎英毅, 原弘真, 大貫貴広, SARENTONGLAGA Borjigin, 福森理加, 長尾慶和, 花園豊, 花園豊, 花園豊  日本異種移植研究会プログラム・抄録集  19th-  31  2017  [Not refereed][Not invited]
  • 阿部 朋行, 河野 正太, 大貫 貴広, 菱川 修司, 國田 智, 花園 豊  Experimental Animals  65-  (4)  345  -351  2016/10  [Not refereed][Not invited]
     
    ブスルファン(BU)は、造血幹細胞移植の前処置に使用される薬剤であり、骨髄抑制の結果として血小板が減少する。本研究では、BUによる急性血小板減少のブタモデルを作出した。マイクロミニブタ(6〜12ヵ月齢、体重8.5〜14.4kg、富士マイクラ)にBU4,6,8mg/kgを静脈内投与し(各々n=1、8、1)、16日間にわたって末梢血の血小板数を測定した。その結果、血小板数はBU投与量に依存して減少したが、6mg/kgのBU投与が血小板減少モデルとして至適と判断された。この至適投与量のBUを投与した場合、血小板数は7日目から低下し、12日目に30,000/μl未満に減少した(最低値14,000/μl、投与15日目)。出血時間は血小板数の減少に伴って延長した(r=-0.63、P<0.01)。白血球数はBU投与後3日目から減少傾向だったが、最低値5,000/μlにとどまり、感染徴候は見られなかった。ヘモグロビン値および血液凝固検査値に著明な変化はなかった。いずれの個体も食欲減退、体重減少、活動性の低下は見られなかった。BU投与16日目では、骨髄有核細胞数および各血球系統コロニー数が有意に低下し、骨髄細胞密度の低下が認められ、予想どおり血小板減少は骨髄抑制に起因するものであった。本ブタモデルは臨床応用をめざした止血製剤の試験等に有用と思われる。(著者抄録)
  • 河野正太, 阿部朋行, 大貫貴広, 花園豊  日本異種移植研究会プログラム・抄録集  18th-  26  2016  [Not refereed][Not invited]
  • 河野正太, 菱川修司, 阿部朋行, 長田直希, 國田智, 花園豊  日本獣医学会学術集会講演要旨集  158回-  441  -441  2015/08  [Not refereed][Not invited]
  • 阿部 朋行  自治医科大学紀要  37-  50  -50  2015/03  [Not refereed][Not invited]
  • 原明日香, 阿部朋行, 三瓶和大, サラン トラガ, 緒方和子, 山口美緒, 福森理加, 長尾慶和  日本畜産学会大会講演要旨  119回-  185  -185  2015/03  [Not refereed][Not invited]
  • Factors affecting hematopoietic engraftment of monkey embryonic stem cells in sheep fetuses.
    Nagao Y, Abe T, Hara A, Ogata K, Yamaguchi M, Sarentonglaga B, Fukumori R, Hanazono Y  Reproduction, Fertility and Development  27-  (1)  255  -255  2015  [Refereed][Not invited]
  • 阿部 朋行, 花園 豊, 長尾 慶和  Experimental Animals  63-  (4)  475  -481  2014/10  [Not refereed][Not invited]
     
    ヒト造血幹細胞(hematopoietic stem cells:HSC)は、免疫不全マウスを用いた造血再構築実験で評価されてきた。しかし、小型・短命のマウスでヒト造血を長期間評価するには限界があることから、大型動物を用いた評価法の確立が望まれる。これまでに我々は、免疫系が未発達なヒツジ胎仔にヒトHSCを移植することで、生後のヒツジ骨髄中においてヒト造血細胞(colony forming unit:CFU)の検出に成功した。今回、このヒツジ子宮内移植系を用いて、ヒト造血幹細胞の生着を長期にわたって評価した。本解析には14頭のヒツジを用いた。そのうち4頭では、HSC増幅遺伝子であるHOXB4をヒトHSCに導入し、移植した。別の4頭では、移植前処置剤であるブスルファンを妊娠ヒツジに投与した後で、ヒトHSCを移植した。移植後5ヵ月において、ヒトHSCにもヒツジにも処置を加えずに移植した6頭ではヒトCFUが検出されなかったが、何らかの処置を加えた残りの8頭中7頭では1-3%の割合でヒトCFUの生着を示した。さらに、HOXB4遺伝子を導入したヒトHSCを移植したヒツジでは、移植後40ヵ月にわたってヒトCFUの生着が維持された。以上より、ヒツジ子宮内移植系を用いることで、マウスの系のような植え継ぎ移植を行わずに、ヒトHSCの生着をヒツジ1個体内で長期的に評価できることが示された。(著者抄録)
  • Tomoyuki Abe, Yutaka Hanazono, Yoshikazu Nagao  Experimental Animals  63-  (4)  475  -481  2014  [Not refereed][Not invited]
     
    Xenograft models of human hematopoiesis are essential to the study of the engraftment and proliferative potential of human hematopoietic stem cells (HSCs) in vivo. Immunodeficient mice and fetal sheep are often used as xenogeneic recipients because they are immunologically naive. In this study, we transplanted human HSCs into fetal sheep and assessed the long-term engraftment of transplanted human HSCs after birth. Fourteen sheep were used in this study. In 4 fetal sheep, HSCs were transduced with homeo-box B4 (HOXB4) gene before transplantation, which promoted the expansion of HSCs. Another 4 fetal sheep were subjected to non-myeloablative conditioning with busulfan. Seven of these 8 sheep showed successful engraftment of human HSCs (1–3% of colony-forming units) as assessed after the birth of fetal sheep (5 months post-transplantation), although HOXB4-transduced HSCs showed sustained engraftment for up to 40 months. Intact HSCs were transplanted into six non-conditioned fetal sheep, and human colony-forming units were not detected in the sheep after birth. These results suggest that, as compared with mouse models, where the short lifespan of mice limits long-term follow-up of HSC engraftment, the fetal sheep model provides a unique perspective for evaluating long-term engraftment and proliferation of human HSCs.
  • Tomoyuki Abe, Shigeo Masuda, Borjigin Sarentonglaga, Kazuko Ogata, Mio Yamaguchi, Satoshi Hayashi, Yoshikazu Nagao, Yutaka Hanazono  XENOTRANSPLANTATION  20-  (5)  342  -342  2013/09  [Not refereed][Not invited]
  • Yoshikazu Nagao, Tomoyuki Abe, Yujiro Tanaka, Kyoko Sasaki, Shigeo Masuda, Borjigin Sarentonglaga, Kazuko Ogata, Mio Yamaguchi, Satoshi Hayashi, Yoshihiro Kitano, Yutaka Hanazono  XENOTRANSPLANTATION  20-  (5)  372  -372  2013/09  [Not refereed][Not invited]
  • 下澤 律浩, 藤城 修平, 水上 喜久, 阿部 朋行, 花園 豊  Journal of Mammalian Ova Research  30-  (2)  S94  -S94  2013/04  [Not refereed][Not invited]
  • 妊娠期ヒツジにおける乳腺組織の構築過程
    原 明日香, 阿部 朋行, サラン・トラガ, 緒方 和子, 長尾 慶和  日本畜産学会大会講演要旨集  116回-  190  -190  2013/03  [Not refereed][Not invited]
  • Y. Nagao, T. Abe, Y. Tanaka, K. Sasaki, S. Masuda, S. Nitta, B. Sarentonglaga, S. Hayashi, Y. Kitano, Y. Hanazono  REPRODUCTION IN DOMESTIC ANIMALS  47-  589  -590  2012/08  [Not refereed][Not invited]
  • Yutaka Hanazono, Tomoyuki Abe, Suguru Nitta, Shigeo Masuda, Satoshi Hayashi, Yoshikazu Nagao  EXPERIMENTAL HEMATOLOGY  40-  (8)  S158  -S158  2012/08  [Not refereed][Not invited]
  • ヒツジ胎子内におけるサルES細胞の生着、造血系分化およびテラトーマ形成に及ぼす要因
    新田 卓, 阿部 朋行, 田中 裕次郎, 佐々木 京子, 増田 茂夫, ボラジギン・サラントラガ, 林 聡, 北野 良博, 花園 豊, 長尾 慶和  The Journal of Reproduction and Development  58-  (Suppl.)  j92  -j92  2012/08  [Not refereed][Not invited]
  • 新規センダイウイルスベクターによるヒト臍帯血造血幹細胞体外増幅法の開発
    増田 茂夫, 花園 豊, 阿部 朋行  大和証券ヘルス財団研究業績集  (35)  21  -25  2012/03  [Not refereed][Not invited]
  • 子宮内移植後のヒツジ体内におけるヒトおよびサル造血の長期生着に及ぼす要因
    新田 卓, 阿部 朋行, 増田 茂夫, 林 聡, 花園 豊, 長尾 慶和  The Journal of Reproduction and Development  57-  (Suppl.)  j113  -j113  2011/08  [Not refereed][Not invited]
  • Shigeo Masuda, Tomoyuki Abe, Satoshi Hayashi, Yujiro Tanaka, Hiroshi Ban, Makoto Inoue, Mamoru Hasegawa, Yoshikazu Nagao, Yutaka Hanazono  BLOOD  116-  (21)  1525  -1525  2010/11  [Not refereed][Not invited]
  • ABE TOMOYUKI, MASUDA SHIGEO, TANAKA YUJIRO, TAKAHASHI HIRONORI, HAYASHI SATOSHI, HANAZONO YUTAKA, NAGAO YOSHIKAZU  J Reprod Dev  56-  (Suppl.)  j68  -j68  2010/08  [Not refereed][Not invited]
  • 増田 茂夫, 阿部 朋行, 井上 誠, 長谷川 護, 林 聡, 長尾 慶和, 花園 豊  自治医科大学紀要  32-  137  -138  2010/03  [Not refereed][Not invited]
  • 周産期乳牛における大豆粕代替としての液化仕込み清酒粕の給与効果
    平澤 遼子, 市瀬 瑞樹, 阿部 朋行, 三瓶 和大, 廣田 真人, 竹内 侑紀, 藤井 一徳, 家藤 治幸, 藤井 力, 安藤 貞, 長尾 慶和  日本畜産学会大会講演要旨集  112回-  43  -43  2010/03  [Not refereed][Not invited]
  • Shigeo Masuda, Tomoyuki Abe, Makoto Inoue, Mamoru Hasegawa, Satoshi Hayashi, Yoshikazu Nagao, Yutaka Hanazono  BLOOD  114-  (22)  290  -290  2009/11  [Not refereed][Not invited]
  • ヒツジ移植系でのHoxB4一過性発現型センダイウイルスベクターによるヒトHSC増幅効果と安全性評価
    増田 茂夫, 阿部 朋行, 井上 誠, 長谷川 護, 林 聡, 長尾 慶和, 花園 豊  臨床血液  50-  (9)  930  -930  2009/09  [Not refereed][Not invited]
  • ヒツジ胎子への子宮内移植によるヒツジ/サルキメラの形成とその免疫学的機構の解明
    阿部 朋行, 田中 裕次郎, 中村 紳一朗, 林 聡, 増田 茂夫, 花園 豊, 長尾 慶和  The Journal of Reproduction and Development  55-  (Suppl.)  j97  -j97  2009/08  [Not refereed][Not invited]
  • サルES細胞の生着および分化誘導に及ぼすヒツジ胎子日齢の影響
    阿部 朋行, 田中 裕次郎, 林 聡, 北野 良博, 花園 豊, 長尾 慶和  The Journal of Reproduction and Development  53-  (Suppl.)  j120  -j120  2007/09  [Not refereed][Not invited]
  • サルES細胞由来の肉眼的組織をもつヒツジの作製
    花園 豊, 田中 裕次郎, 中村 紳一朗, 岸 友紀子, 池田 たま子, 柴田 宏昭, 佐々木 京子, 阿部 朋行, 林 聡, 北野 良博, 長尾 慶和  臨床血液  48-  (9)  904  -904  2007/09  [Not refereed][Not invited]
  • ヒツジにおける骨髄抑制誘導のためのbusulfan至適投与量の検討
    阿部 朋行, 田中 裕次郎, 林 聡, 北野 良博, 花園 豊, 長尾 慶和  日本獣医学会学術集会講演要旨集  144回-  143  -143  2007/08  [Not refereed][Not invited]
  • ウシ胎子期および成体泌乳期乳腺細胞の形態および機能解析
    阿部 朋行, 綾川 宏教, 青山 真人, 杉田 昭栄, 長尾 慶和  日本獣医学会学術集会講演要旨集  143回-  204  -204  2007/03  [Not refereed][Not invited]

Industrial Property Rights

Research Grants & Projects

  • ヒツジ胎仔造血環境下でのヒトiPS細胞由来造血幹細胞の発生機序の解明とその応用
    日本学術振興会:科学研究費助成事業 基盤研究(C)
    Date (from‐to) : 2018/04 -2021/03 
    Author : 阿部 朋行
     
    骨髄や臍帯血を用いた造血幹細胞移植は、がん治療や細胞移植のための有効な治療手段である。造血幹細胞のドナー不足が続く近年、新たな移植細胞源としてiPS細胞の活用が期待されているものの、iPS細胞の造血幹細胞への分化誘導はいまだに難しいのが現状である。このような背景の中で申請者らは、妊娠早期のヒツジ胎仔が免疫寛容を誘導することを利用し、造血発生の場である肝臓内でヒトiPS細胞由来の中胚葉細胞から造血幹細胞を分化させることに成功した(特願2015-168702)。しかしながら、ヒツジ胎仔肝臓内でのヒト造血幹細胞の産生・分化のメカニズムは明らかにできていない。そこで本研究では、(1)ヒツジ胎仔体内でのヒト中胚葉細胞の動態・変化を明らかにし、ヒツジ造血支持細胞との共培養系を用いて(2)造血幹細胞の産生・分化に寄与する因子を抽出することで、試験管内での造血幹細胞への分化誘導技術の開発を目指す。 初年度は、ヒトiPS細胞由来の中胚葉細胞を移植した後でヒツジ胎仔肝臓や骨髄の組織切片を作製し、汎血球マーカーであるCD45、Notch経路活性化のマーカーであるN1ICDに対する抗体を用いて免疫染色を行うことで、ヒトiPS細胞由来の中胚葉細胞のヒツジ胎仔体内における動態を解析した。その結果、移植後に移植細胞ではCD45を陽性化し、Notchシグナルが活性化していることを明らかにした。また、造血発生に関与することが推測されるヒツジ胎仔組織として、肝臓、骨髄および血管内皮組織を採取し、支持細胞の初代培養ならびにこれらの不死化に成功した。
  • ヒツジ胎仔造血環境下でのヒトiPS細胞由来造血幹細胞の発生機序の解明とその応用
    文部科学省:科学研究費補助金(基盤研究(C))
    Date (from‐to) : 2018/04 -2021/03 
    Author : 阿部朋行
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2014/04 -2019/03 
    Author : NAGAO YOSHIKAZU, HANAZONO Yutaka, ABE Tomoyuki
     
    Hematopoietic engraftment has been shown to observe when early differentiated monkey ES cells were transplanted into fetal liver. In this study, we examined optimal condition of ovine fetal liver for hematopoietic differentiation of the human iPS cells. We found that human hematopoietic chimera sheep can be efficiently generated when mesodermal early differentiated human iPS cells were injected into ovine fetal liver at 50-60 days of gestation. The human hematopoietic tissue was observed in ovine bone marrow for at least 4 years.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    Date (from‐to) : 2016/04 -2018/03 
    Author : Abe Tomoyuki, HANAZONO Yutaka, NAGAO Yoshikazu
     
    Generating hematopoietic stem cells (HSCs) from human iPSCs has been a great challenge. We hypothesized some key environmental factors are missing in vitro. Therefore, we tried in vivo generation of HSCs from human iPSCs. In this study, we generated human/sheep hematopoietic chimera; that is, sheep that have human HSCs derived from human iPSCs. Human iPSCs were cultured on murine stromal OP9 cells with multiple cytokines for 6 days for differentiation to a hematopoietic lineage. The cells were then transplanted into the liver of busulfan-conditioned fetal sheep. The engraftment of human hematopoietic cells was quantitatively evaluated by PCR of colony-forming units. Considering that many researchers have long failed to generate engraftable HSCs from human iPSCs, the data here imply that the acquisition of hematopoietic engraftment ability of human iPSCs may depend on the in vivo microenvironment such as in the fetal sheep liver. We are now taking out human HSCs from the sheep.
  • ヒツジ体内を介したヒトiPS細胞由来の機能的造血幹細胞の作製・増幅技術の開発
    文部科学省:科学研究費補助金(若手研究(B))
    Date (from‐to) : 2016/04 -2018/03 
    Author : 阿部朋行
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    Date (from‐to) : 2013/04 -2015/03 
    Author : ABE Tomoyuki
     
    The generation of definitive (engraftable) human hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) has been a major challenge in hematology. We are trying to generate hematopoietic chimera in sheep with human iPSCs.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2012/04 -2015/03 
    Author : HANAZONO Yutaka, NAGAO Yosikazu, ABE Tomoyuki
     
    X-linked severe combined immunodeficiency has been successfully treated in US and European countries by in utero transplantation (IUT) of hematopoietic stem cells; however, the engraftment efficiency has not necessarily been high enough for other diseases in which graft cells do not have growth advantage. From a series of experiments in the setting of sheep IUT, we have shown that the engraftment efficiency can be improved by the following methods: (1) Pre-conditioning of fetuses with busulfan, (2) transient forced expression of the HoxB4 gene in donor hematopoietic stem cells, and (3) post-conditioning with cytokines.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity start-up
    Date (from‐to) : 2011 -2012 
    Author : ABE Tomoyuki
     
    We have shown the safety and effectiveness of treatment with busulfan in sheep and have suggested a conditioning regimen with busulfan for sheep in utero transplantation involving intravenous administration of 3 mg/kg busulfan to pregnant ewes 6 days befo


Copyright © MEDIA FUSION Co.,Ltd. All rights reserved.