研究者業績

KUMANO KEIKI

  (熊野 恵城)

Profile Information

Affiliation
Musashino University
Degree
博士(医学)(Mar, 1999, 東京大学)

J-GLOBAL ID
201801003635316249
researchmap Member ID
B000327851

Papers

 104
  • Kazuhiko Ishigaki, Keiki Kumano, Kyohei Fujita, Hiroo Ueno
    Scientific Reports, 11(1), Dec, 2021  
    <title>Abstract</title>Although the physiological function of the omentum remains elusive, it has been proposed that it plays an important role in fat storage, immune regulation, and regeneration of injured tissues and organs. Although the omentum undergoes expansion upon activation, reports on the accurate assessment of increased cell types and the origin of the increased cells remain limited. To investigate this aspect, the omenta of parabiotic mice were subjected to activation using distinct fluorescent markers and single-cell RNA sequencing (scRNA-seq) was performed to identify circulation-derived omental cells. We found that a considerable number of circulating cells contributed to the activation of the omentum. The omental cells derived from circulating cells exhibited morphological features similar to those of fibroblasts. scRNA-seq revealed the existence of a novel cell population that co-expressed macrophage and fibroblast markers in the activated omentum, suggesting that it corresponded to circulating macrophage-derived fibroblast-like cells. Lineage tracing experiments revealed that most fibroblasts in the activated omentum were not derived from WT1-positive mesenchymal progenitors. The cell cluster also expressed various chemokine genes, indicating its role in the activation and recruitment of immune cells. These results provide important information regarding the activation of the omentum.
  • Matsukawa, T, Yamamoto, T, Honda, A, Toya, T, Ishiura, H, Mitsui, J, Tanaka, M, Hao, A, Shinohara, A, Ogura, M, Kataoka, K, Seo, S, Kumano, K, Hosoi, M, Narukawa, N, Yasunaga, A, Maki, H, Ichikawa, M, Nannya, Y, Imai, Y, Takahashi, T, Takahashi, Y, Nagasako, Y, Yasaka, K, Koshi Mano K, Kawabe Matsukawa, M, Miyagawa, T, Hamada, M, Sakuishi, K, Hayashi, T, Iwata, A, Terao, Y, Shimizu, J, Goto, J, Mori, M, Kunimatsu, A, Aoki, S, Hayashi, S, Nakamura, F, Arai, S, Monma, K, Ogata, K, Yoshida, T, Abe, O, Inazawa, J, Toda, T, Kurokawa, M, Tsuji, S
    Brain Communications, 2(1) fcz048, Jan, 2020  Peer-reviewed
    <title>Abstract</title> Accumulated experience supports the efficacy of allogenic haematopoietic stem cell transplantation in arresting the progression of childhood-onset cerebral form of adrenoleukodystrophy in early stages. For adulthood-onset cerebral form of adrenoleukodystrophy, however, there have been only a few reports on haematopoietic stem cell transplantation and the clinical efficacy and safety of that for adulthood-onset cerebral form of adrenoleukodystrophy remain to be established. To evaluate the clinical efficacy and safety of haematopoietic stem cell transplantation, we conducted haematopoietic stem cell transplantation on 12 patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy in a single-institution-based prospective study. Through careful prospective follow-up of 45 male adrenoleukodystrophy patients, we aimed to enrol patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy at early stages. Indications for haematopoietic stem cell transplantation included cerebral form of adrenoleukodystrophy or cerebello-brainstem form of adrenoleukodystrophy with Loes scores up to 13, the presence of progressively enlarging white matter lesions and/or lesions with gadolinium enhancement on brain MRI. Clinical outcomes of haematopoietic stem cell transplantation were evaluated by the survival rate as well as by serial evaluation of clinical rating scale scores and neurological and MRI findings. Clinical courses of eight patients who did not undergo haematopoietic stem cell transplantation were also evaluated for comparison of the survival rate. All the patients who underwent haematopoietic stem cell transplantation survived to date with a median follow-up period of 28.6 months (4.2–125.3 months) without fatality. Neurological findings attributable to cerebral/cerebellar/brainstem lesions became stable or partially improved in all the patients. Gadolinium-enhanced brain lesions disappeared or became obscure within 3.5 months and the white matter lesions of MRI became stable or small. The median Loes scores before haematopoietic stem cell transplantation and at the last follow-up visit were 6.0 and 5.25, respectively. Of the eight patients who did not undergo haematopoietic stem cell transplantation, six patients died 69.1 months (median period; range 16.0–104.1 months) after the onset of the cerebral/cerebellar/brainstem lesions, confirming that the survival probability was significantly higher in patients with haematopoietic stem cell transplantation compared with that in patients without haematopoietic stem cell transplantation (P = 0.0089). The present study showed that haematopoietic stem cell transplantation was conducted safely and arrested the inflammatory demyelination in all the patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy when haematopoietic stem cell transplantation was conducted in the early stages. Further studies are warranted to optimize the procedures of haematopoietic stem cell transplantation for adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy.
  • Taoka K, Arai S, Kataoka K, Hosoi M, Miyauchi M, Yamazaki S, Honda A, Aixinjueluo W, Kobayashi T, Kumano K, Yoshimi A, Otsu M, Niwa A, Nakahata T, Nakauchi H, Kurokawa M
    Scientific reports, 8(1) 15855-15855, Oct 26, 2018  Peer-reviewed
    Chronic myelomonocytic leukemia (CMML) is an entity of myelodysplastic syndrome/myeloproliferative neoplasm. Although CMML can be cured with allogeneic stem cell transplantation, its prognosis is generally very poor due to the limited efficacy of chemotherapy and to the patient's age, which is usually not eligible for transplantation. Comprehensive analysis of CMML pathophysiology and the development of therapeutic agents have been limited partly due to the lack of cell lines in CMML and the limited developments of mouse models. After successfully establishing patient's derived disease-specific induced pluripotent stem cells (iPSCs) derived from a patient with CMML, we utilized these CMML-iPSCs to achieve hematopoietic re-differentiation in vitro, created a humanized CMML mouse model via teratomas, and developed a drug-testing system. The clinical characteristics of CMML were recapitulated following hematopoietic re-differentiation in vitro and a humanized CMML mouse model in vivo. The drug-testing system using CMML-iPSCs identified a MEK inhibitor, a Ras inhibitor, and liposomal clodronate as potential drugs for treating CMML. Clodronate is a drug commonly used as a bisphosphonate for osteoporosis. In this study, the liposomalization of clodronate enhanced its effectiveness in these assays, suggesting that this variation of clodronate may be adopted as a repositioned drug for CMML therapy.
  • Masashi Miyauchi, Junji Koya, Shunya Arai, Sho Yamazaki, Akira Honda, Keisuke Kataoka, Akihide Yoshimi, Kazuki Taoka, Keiki Kumano, Mineo Kurokawa
    Stem cell reports, 10(3) 1115-1130, Mar 13, 2018  Peer-reviewed
    Properties of cancer stem cells involved in drug resistance and relapse have significant effects on clinical outcome. Although tyrosine kinase inhibitors (TKIs) have dramatically improved survival of patients with chronic myeloid leukemia (CML), TKIs have not fully cured CML due to TKI-resistant CML stem cells. Moreover, relapse after discontinuation of TKIs has not been predicted in CML patients with the best TKI response. In our study, a model of CML stem cells derived from CML induced pluripotent stem cells identified ADAM8 as an antigen of TKI-resistant CML cells. The inhibition of expression or metalloproteinase activity of ADAM8 restored TKI sensitivity in primary samples. In addition, residual CML cells in patients with optimal TKI response were concentrated in the ADAM8+ population. Our study demonstrates that ADAM8 is a marker of residual CML cells even in patients with optimal TKI response and would be a predictor of relapse and a therapeutic target of TKI-resistant CML cells.
  • Hirotsugu Yanai, Naho Atsumi, Toshihiro Tanaka, Naohiro Nakamura, Yoshihiro Komai, Taichi Omachi, Kiyomichi Tanaka, Kazuhiko Ishigaki, Kazuho Saiga, Haruyuki Ohsugi, Yoko Tokuyama, Yuki Imahashi, Shuichi Ohe, Hiroko Hisha, Naoko Yoshida, Keiki Kumano, Masanori Kon, Hiroo Ueno
    SCIENTIFIC REPORTS, 7(1) 9891, Aug, 2017  Peer-reviewed
    The murine intestine, like that of other mammalians, continues to develop after birth until weaning; however, whether this occurs in response to an intrinsic developmental program or food intake remains unclear. Here, we report a novel system for the allotransplantation of small intestine and colon harvested from Lgr5(EGFP-IRES-CreERT2/+); Ros alpha 26(rbw/+) mice immediately after birth into the subrenal capsule of wild-type mice. By histological and immunohistochemical analysis, the developmental process of transplanted small intestine and colon was shown to be comparable with that of the native tissues: mature intestines equipped with all cell types were formed, indicating that these organs do not require food intake for development. The intestinal stem cells in transplanted tissues were shown to self-renew and produce progeny, resulting in the descendants of the stem cells occupying the crypt-villus unit of the small intestine or the whole crypt of the colon. Collectively, these findings indicate that neonatal intestine development follows an intrinsic program even in the absence of food stimuli.

Misc.

 45
  • 並河 健, 菅野 渉平, 齋賀 一歩, 石垣 和彦, 田中 聖道, 鷲尾 隆太, 山内 壮作, 熊野 恵城, 上野 博夫
    診断病理, 35(1) 34-40, Jan, 2018  
    6ヵ月20日の男児。在胎34週5日、体重1,726gで出生した。Down症候群・TAMと診断され、Ara-Cによる加療を受けたが、日齢185日に呼吸状態が悪化し死亡した。末梢血には日齢1〜15日に芽球が出現し、一旦は消失するが、剖検時の骨髄では20%以上の芽球を認めた。それらはMPO(+)かつCD61(-)で、FAB分類ではDown症候群に典型的なM7ではなくM2を示唆するものであった。肺高血圧症と複合要因により呼吸不全に至った症例であった。その経過について考察を交えて報告する。(著者抄録)
  • Takashi Matsukawa, Tomotaka Yamamoto, Takashi Toya, Akihito Shinohara, Yasuhito Nanya, Sachiko Seo, Keiki Kumano, Motoshi Ichikawa, Yuji Takahashi, Hiroyuki Ishiura, Jun Mitsui, Masaki Tanaka, Mineo Kurokawa, Shoji Tsuji
    ANNALS OF NEUROLOGY, 80 S201-S201, Oct, 2016  
  • Shuichi Ohe, Toshihiro Tanaka, Hirotsugu Yanai, Yoshihiro Komai, Taichi Omachi, Shohei Kanno, Kiyomichi Tanaka, Kazuhiko Ishigaki, Kazuho Saiga, Naohiro Nakamura, Haruyuki Ohsugi, Yoko Tokuyama, Naho Atsumi, Hiroko Hisha, Naoko Yoshida, Keiki Kumano, Fumikazu Yamazaki, Hiroyuki Okamoto, Hiroo Ueno
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 472(1) 292-292, Mar, 2016  
  • 田中 敏宏, 駒井 資弘, 徳山 陽子, 矢内 洋次, 大江 秀一, 大町 太一, 田中 聖道, 石垣 和彦, 金 桂花, 厚海 奈穂, 菅野 渉平, 吉田 真子, 比舎 弘子, 熊野 恵城, 上野 博夫
    Cytometry Research, 24(Suppl.) 58-58, Jun, 2014  
  • 比舎 弘子, 田中 敏宏, 菅野 渉平, 徳山 陽子, 駒井 資弘, 大江 秀一, 矢内 洋次, 大町 太一, 石垣 和彦, 田中 聖道, 厚海 奈穂, 吉田 直子, 熊野 恵城, 上野 博夫
    日本病理学会会誌, 103(1) 274-274, Mar, 2014  

Books and Other Publications

 2

Major Presentations

 30

Teaching Experience

 20

Research Projects

 22