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MIYANISHI Masanori
Graduate School of Medicine / Faculty of Medical Sciences
Professor

Researcher basic information

■ Research Keyword
  • スクリーニング
  • 造血幹細胞
■ Research Areas
  • Life sciences / Hematology and oncology
  • Life sciences / Medical biochemistry

Research activity information

■ Paper
  • Allison Banuelos, Allison Zhang, Hala Berouti, Michelle Baez, Leyla Yılmaz, Nardin Georgeos, Kristopher D Marjon, Masanori Miyanishi, Irving L Weissman
    The use of colony-stimulating factor-1 receptor (CSF1R) inhibitors has been widely explored as a strategy for cancer immunotherapy due to their robust depletion of tumor-associated macrophages (TAMs). While CSF1R blockade effectively eliminates TAMs from the solid tumor microenvironment, its clinical efficacy is limited. Here, we use an inducible CSF1R knockout model to investigate the persistence of tumor progression in the absence of TAMs. We find increased frequencies of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the bone marrow, throughout circulation, and in the tumor following CSF1R deletion and loss of TAMs. We find that G-MDSCs are capable of suppressing macrophage phagocytosis, and the elimination of G-MDSCs through CXCR2 inhibition increases macrophage capacity for tumor cell clearance. Further, we find that combination therapy of CXCR2 inhibition and CD47 blockade synergize to elicit a significant anti-tumor response. These findings reveal G-MDSCs as key drivers of tumor immunosuppression and demonstrate their inhibition as a potent strategy to increase macrophage phagocytosis and enhance the anti-tumor efficacy of CD47 blockade in B16-F10 melanoma.
    Jan. 2024, Proceedings of the National Academy of Sciences of the United States of America, 121(5) (5), e2318534121, English, International magazine
    Scientific journal

  • Katsuyuki Nishi, Akiomi Nagasaka, Taro Sakamaki, Kay Sadaoka, Masanori Miyanishi
    Self-renewal capacity and multi-lineage differentiation potential are generally regarded as the defining characteristics of hematopoietic stem cells (HSCs). However, numerous studies have suggested that functional heterogeneity exists in the HSC compartment. Recent single-cell analyses have reported HSC clones with different cell fates within the HSC compartment, which are referred to as biased HSC clones. The mechanisms underlying heterogeneous or poorly reproducible results are little understood, especially regarding the length of self-renewal when purified HSC fractions are transplanted by conventional immunostaining. Therefore, establishing a reproducible isolation method for long-term HSCs (LT-HSCs) and short-term HSCs (ST-HSCs), defined by the length of their self-renewal, is crucial for overcoming this issue. Using unbiased multi-step screening, we identified a transcription factor, Hoxb5, which may be an exclusive marker of LT-HSCs in the mouse hematopoietic system. Based on this finding, we established a Hoxb5 reporter mouse line and successfully isolated LT-HSCs and ST-HSCs. Here we describe a detailed protocol for the isolation of LT-HSCs and ST-HSCs using the Hoxb5 reporter system. This isolation method will help researchers better understand the mechanisms of self-renewal and the biological basis for such heterogeneity in the HSC compartment.
    May 2023, Journal of visualized experiments : JoVE, (195) (195), English, International magazine
    Scientific journal

  • Katsuyuki Nishi, Taro Sakamaki, Kay Sadaoka, Momo Fujii, Akifumi Takaori-Kondo, James Y Chen, Masanori Miyanishi
    Historically, defining haematopoietic subsets, including self-renewal, differentiation and lineage restriction, has been elucidated by transplanting a small number of candidate cells with many supporting bone marrow (BM) cells. While this approach has been invaluable in characterising numerous distinct subsets in haematopoiesis, this approach is arguably flawed. The haematopoietic stem cell (HSC) has been proposed as the critical haematopoietic subset necessary for transplantation. However, due to the presence of supporting cells, the HSC has never demonstrated sufficiency. Utilising the homeobox B5 (Hoxb5)-reporter system, we found that neither long-term (LT) HSCs nor short-term (ST) HSCs alone were sufficient for long-term haematopoietic reconstitution. Critically, reconstitution can be rescued by transplanting combined LT- and ST-HSCs, without supporting cells; a fraction we term the 'Minimum Subset for Transplantation' (MST). The MST accounts for only 0·005% of nucleated cells within mouse BM, and this MST can be cultured, expanded and genetically modified while preserving its rapid haematopoietic engraftment potential. These results support the consideration of an MST approach for clinical translation, especially for gene therapy approaches that require HSC compartment modification.
    Feb. 2022, British journal of haematology, 196(3) (3), 711 - 723, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Makoto Iwasaki, Junya Kanda, Yasuyuki Arai, Tadakazu Kondo, Takayuki Ishikawa, Yasunori Ueda, Kazunori Imada, Takashi Akasaka, Akihito Yonezawa, Kazuhiro Yago, Masaharu Nohgawa, Naoyuki Anzai, Toshinori Moriguchi, Toshiyuki Kitano, Mitsuru Itoh, Nobuyoshi Arima, Tomoharu Takeoka, Mitsumasa Watanabe, Hirokazu Hirata, Kosuke Asagoe, Isao Miyatsuka, Le My An, Masanori Miyanishi, Akifumi Takaori-Kondo
    Graft-versus-host-disease-free, relapse-free survival (GRFS) is a useful composite endpoint that measures survival without relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to develop a novel analytical method that appropriately handles right-censored data and competing risks to understand the risk for GRFS and each component of GRFS. This study was a retrospective data-mining study on a cohort of 2207 adult patients who underwent their first allo-HSCT at the Kyoto Stem Cell Transplantation Group (KSCTG), a multi-institutional joint research group of 17 transplantation centers in Japan. The primary endpoint was GRFS. A stacked ensemble of Cox proportional hazard regression and seven machine learning algorithms was applied to develop a prediction model. The median age of patients was 48 years. For GRFS, the stacked ensemble model achieved better predictive accuracy evaluated by C-index than other top-of-the-art competing risk models (ensemble model: 0.670, Cox-PH: 0.668, Random Survival Forest: 0.660, Dynamic DeepHit: 0.646). The probability of GRFS after 2 years was 30.54% for the high-risk and 40.69% for the low-risk group, respectively (hazard ratio [HR] compared to the low-risk group: 2.127; 95% CI: 1.19-3.80). We developed a novel predictive model for survival analysis that showed superior risk stratification to existing methods using a stacked ensemble of multiple machine learning algorithms.
    Dec. 2021, Blood advances, English, International magazine
    [Refereed]
    Scientific journal

  • Taro Sakamaki, Kevin S Kao, Katsuyuki Nishi, James Y Chen, Kay Sadaoka, Momo Fujii, Akifumi Takaori-Kondo, Irving L Weissman, Masanori Miyanishi
    Self-renewal and multipotency are essential functions of hematopoietic stem cells (HSCs). To maintain homeostatic hematopoiesis, functionally uniform HSCs have been thought to be an ideal cell-of-origin. Recent technological advances in the field have allowed us to analyze HSCs with single cell resolution and implicate that functional heterogeneity may exist even within the highly purified HSC compartment. However, due in part to the technical limitations of analyzing extremely rare populations and our incomplete understanding of HSC biology, neither the biological meaning of why heterogeneity exists nor the precise mechanism of how heterogeneity is determined within the HSC compartment is entirely known. Here we show the first evidence that self-renewal capacity varies with the degree of replication stress dose and results in heterogeneity within the HSC compartment. Using the Hoxb5-reporter mouse line which enables us to distinguish between long-term (LT)-HSCs and short-term (ST)-HSCs, we have found that ST-HSCs quickly lose self-renewal capacity under high stress environments but can maintain self-renewal under low stress environments for long periods of time. Critically, exogeneous Hoxb5 expression confers protection against loss of self-renewal to Hoxb5-negative HSCs and can partially alter the cell fate of ST-HSCs to that of LT-HSCs. Our results demonstrate that Hoxb5 imparts functional heterogeneity in the HSC compartment by regulating self-renewal capacity. Additionally, Hoxb5-positive HSCs may exist as fail-safe system to protect from the exhaustion of HSCs throughout an organism's lifespan.
    Feb. 2021, Biochemical and biophysical research communications, 539, 34 - 41, English, International magazine
    [Refereed]
    Scientific journal

  • Akihiro Tamura, Shotaro Inoue, Takeshi Mori, Jun Noguchi, Sayaka Nakamura, Atsuro Saito, Aiko Kozaki, Toshiaki Ishida, Kay Sadaoka, Daiichiro Hasegawa, Yoshiyuki Kosaka, Masanori Miyanishi
    Despite the growing evidences that immune dysfunction contributes to tumor progression, the prognostic value in patients with neuroblastoma regarding circulating immune blood cell counts has not been well characterized. To answer this, we conducted a retrospective study to evaluate the prognostic value of the circulating immune cell counts at diagnosis in a cohort of 55 patients with neuroblastoma. Based on a novel index by multiplying the absolute monocyte count (AMC)/μl and absolute lymphocyte count (ALC)/μl, we sub-grouped patients with AMC × ALC ≥ 1 × 106 (/μl)2 as high group and patients with AMC × ALC < 1 × 106 (/μl)2 as low group. In the entire cohort, the 4-year progression-free survival (PFS), and overall survival (OS) for high group (n = 38) vs low group (n = 17) was 81.7% (95%CI; 63.6-91.3%) and 90.7% (95%CI; 73.8-96.9%) vs 31.7% (11.6-54.1%) and 56.5% (29.7-76.4%; p < 0.001 for PFS and p = 0.015 for OS), respectively, suggesting that a low AMC × ALC is associated with poor prognosis. In the subgroup analysis for high-risk patients, the 4-year PFS and OS for high group (n = 17) vs low group (n = 13) was 59.8% (31.2-79.7%) and 79.8% (49.4-93.0%) vs 8.5% (0.5-31.7%) and 42.0% (15.4-66.8%; p < 0.001 for PFS and p = 0.089 for OS), respectively. Our data demonstrate that AMC × ALC at diagnosis is a cost-effective and easily measurable biomarker for predicting prognosis in neuroblastoma.
    2020, Frontiers in oncology, 10, 572413 - 572413, English, International magazine
    [Refereed]
    Scientific journal

  • Tsai JM, Shoham M, Fernhoff NB, George BM, Marjon KD, McCracken MN, Kao KS, Sinha R, Volkmer AK, Miyanishi M, Seita J, Rinkevich Y, Weissman IL
    Sep. 2019, Blood advances, 3(18) (18), 2713 - 2721
    [Refereed]

  • Soichiro Takagaki, Rieko Yamashita, Noriyoshi Hashimoto, Kazushi Sugihara, Kanako Kanari, Keisuke Tabata, Toshikazu Nishie, Shogo Oka, Masanori Miyanishi, Chie Naruse, Masahide Asano
    The role of carbohydrate chains in leukocyte migration to inflamed sites during inflammation and trafficking to the lymph nodes under physiological conditions has been extensively characterized. Here, we report that carbohydrate chains also mediate the homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) to the bone marrow (BM). In particular, we found that transplanted BM cells deficient in β-1,4-galactosyltransferase-1 (β4GalT-1) could not support survival in mice exposed to a lethal dose of irradiation. BM cells obtained from mice deficient in β4GalT-1 showed normal colony-forming activity and hematopoietic stem cell numbers. However, colony-forming cells were markedly rare in the BM of recipient mice 24 h after transplantation of β4GalT-1-deficient BM cells, suggesting that β4GalT-1 deficiency severely impairs homing. Similarly, BM cells with a point mutation in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene, encoding a key enzyme in sialic acid biosynthesis, showed mildly impaired homing and engraftment abilities. These results imply that the galactosyl, but not sialyl residues in glycoproteins, are essential for the homing and engraftment of HSPCs to the BM. These findings suggest the possibility of modifying carbohydrate structures on the surface of HSPCs to improve their homing and engraftment to the BM in clinical application.
    May 2019, Scientific reports, 9(1) (1), 7133 - 7133, English, International magazine
    [Refereed]
    Scientific journal

  • Sakamaki T, Miyanishi M
    2019, [Rinsho ketsueki] The Japanese journal of clinical hematology, 60(9) (9), 1056 - 1062
    [Refereed]

  • Szade K, Gulati GS, Chan CKF, Kao KS, Miyanishi M, Marjon KD, Sinha R, George BM, Chen JY, Weissman IL
    Jul. 2018, Antioxidants & redox signaling, 29(2) (2), 191 - 204
    [Refereed]

  • James Y. Chen, Masanori Miyanishi, Sean K. Wang, Satoshi Yamazaki, Rahul Sinha, Kevin S. Kao, Jun Seita, Debashis Sahoo, Hiromitsu Nakauchi, Irving L. Weissman
    Haematopoietic stem cells (HSCs) are arguably the most extensively characterized tissue stem cells. Since the identification of HSCs by prospective isolation(1), complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology, including self-renewal(2-4), differentiation, ageing, niche(5), and diversity(6-8). Here we demonstrate by unbiased multi-step screening, identification of a single gene, homeobox B5 (Hoxb5, also known as Hox-2.1), with expression in the bone marrow that is limited to long-term (LT)-HSCs in mice. Using a mouse single-colour tri-mCherry reporter driven by endogenous Hoxb5 regulation, we show that only the Hoxb5(+) HSCs exhibit long-term reconstitution capacity after transplantation in primary transplant recipients and, notably, in secondary recipients. Only 7-35% of various previously defined immunophenotypic HSCs are LT-HSCs. Finally, by in situ imaging of mouse bone marrow, we show that >94% of LT-HSCs (Hoxb5(+)) are directly attached to VE-cadherin(+) cells, implicating the perivascular space as a near-homogenous location of LT-HSCs.
    NATURE PUBLISHING GROUP, Feb. 2016, NATURE, 530(7589) (7589), 223 - +, English
    [Refereed]
    Scientific journal

  • Masanori Miyanishi, Yasuo Mori, Jun Seita, James Y. Chen, Seth Karten, Charles K. F. Chan, Hiromitsu Nakauchi, Irving L. Weissman
    Very small embryonic-like stem cells (VSELs) isolated from bone marrow (BM) have been reported to be pluripotent. Given their nonembryonic source, they could replace blastocyst-derived embryonic stem cells in research and medicine. However, their multiple-germ-layer potential has been incompletely studied. Here, we show that we cannot find VSELs in mouse BM with any of the reported stem cell potentials, specifically for hematopoiesis. We found that: (1) most events within the "VSEL'' flow-cytometry gate had little DNA and the cells corresponding to these events (2) could not form spheres, (3) did not express Oct4, and (4) could not differentiate into blood cells. These results provide a failure to confirm the existence of pluripotent
    CELL PRESS, Aug. 2013, STEM CELL REPORTS, 1(2) (2), 198 - 208, English
    [Refereed]
    Scientific journal

  • Diane Tseng, Jens-Peter Volkmer, Stephen B. Willingham, Humberto Contreras-Trujillo, John W. Fathman, Nathaniel B. Fernhoff, Jun Seita, Matthew A. Inlay, Kipp Weiskopf, Masanori Miyanishi, Irving L. Weissman
    Mobilization of the T-cell response against cancer has the potential to achieve long-lasting cures. However, it is not known how to harness antigen-presenting cells optimally to achieve an effective antitumor T-cell response. In this study, we show that anti-CD47 antibody-mediated phagocytosis of cancer by macrophages can initiate an antitumor T-cell immune response. Using the ovalbumin model antigen system, anti-CD47 antibody-mediated phagocytosis of cancer cells by macrophages resulted in increased priming of OT-I T cells [cluster of differentiation 8-positive (CD8(+))] but decreased priming of OT-II T cells (CD4(+)). The CD4(+) T-cell response was characterized by a reduction in forkhead box P3-positive (Foxp3(+)) regulatory T cells. Macrophages following anti-CD47-mediated phagocytosis primed CD8(+) T cells to exhibit cytotoxic function in vivo. This response protected animals from tumor challenge. We conclude that anti-CD47 antibody treatment not only enables macrophage phagocytosis of cancer but also can initiate an antitumor cytotoxic T-cell immune response.
    NATL ACAD SCIENCES, Jul. 2013, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110(27) (27), 11103 - 11108, English
    [Refereed]
    Scientific journal

  • Masanori Miyanishi, Katsumori Segawa, Shigekazu Nagata
    Phagocytes, including macrophages, recognize phosphatidylserine exposed on apoptotic cells as an eat me signal. Milk Fat Globule EGF Factor VIII (MFG-E8) is secreted by one subset of macrophages, whereas Tim4, a type I membrane protein, is expressed by another. These proteins bind tightly to phosphatidylserine on apoptotic cells and enhance their engulfment by macrophages. To study the contribution of these proteins to the engulfment of apoptotic cells, we established a mouse line that was deficient in the genes encoding MFG-E8 and Tim4. The null mutation of Tim4 impaired the ability of resident peritoneal macrophages, but not thioglycollate-elicited macrophages, to engulf apoptotic cells. Mice deficient in either MFG-E8 or Tim4 on the C57BL/6 background developed hardly any autoantibodies, but aged female mice deficient in both MFG-E8 and Tim4 developed autoantibodies in an age-dependent manner. Tumour necrosis factor (TNF) is known to protect against systemic lupus erythematosus-type autoimmunity, whereas type I IFN accelerates the disease. Indeed, the administration of an anti-TNF antibody or a reagent that stimulates the IFN- production [2,6,10,14-tetramethylpentadecane (TMPD; also known as pristane)] enhanced the production of autoantibodies in the MFG-E8- and Tim4-double-deficient mice. These results suggest that the double deficiency of Tim4 and MFG-E8, phosphatidylserine-binding proteins, can trigger autoimmunity and that TNF and type I IFN regulate reciprocally the development of autoimmune disease.
    OXFORD UNIV PRESS, Sep. 2012, INTERNATIONAL IMMUNOLOGY, 24(9) (9), 551 - 559, English
    [Refereed]
    Scientific journal

  • Rikinari Hanayama, Masanori Miyanishi, Hiroshi Yamaguchi, Jun Suzuki, Shigekazu Nagata
    John Wiley & Sons, Ltd, Dec. 2009, Cell Death (Wiley), 165 - 175
    [Invited]

  • Masanori Miyanishi, Kazutoshi Tada, Masato Koike, Yasuo Uchiyama, Toshio Kitamura, Shigekazu Nagata
    In programmed cell death, a large number of cells undergo apoptosis, and are engulfed by macrophages to avoid the release of noxious materials from the dying cells(1,2). In definitive erythropoiesis, nuclei are expelled from erythroid precursor cells and are engulfed by macrophages. Phosphatidylserine is exposed on the surface of apoptotic cells(3) and on the nuclei expelled from erythroid precursor cells(4); it works as an 'eat me' signal for phagocytes(5,6). Phosphatidylserine is also expressed on the surface of exosomes involved in intercellular signalling(7). Here we established a library of hamster monoclonal antibodies against mouse peritoneal macrophages, and found an antibody that strongly inhibited the phosphatidylserine-dependent engulfment of apoptotic cells. The antigen recognized by the antibody was identified by expression cloning as a type I transmembrane protein called Tim4 (T-cell immunoglobulin- and mucin-domain-containing molecule; also known as Timd4)(8). Tim4 was expressed in Mac1(+) cells in various mouse tissues, including spleen, lymph nodes and fetal liver. Tim4 bound apoptotic cells by recognizing phosphatidylserine via its immunoglobulin domain. The expression of Tim4 in fibroblasts enhanced their ability to engulf apoptotic cells. When the anti-Tim4 monoclonal antibody was administered into mice, the engulfment of apoptotic cells by thymic macrophages was significantly blocked, and the mice developed autoantibodies. Among the other Tim family members, Tim1, but neither Tim2 nor Tim3, specifically bound phosphatidylserine. Tim1- or Tim4-expressing Ba/F3 B cells were bound by exosomes via phosphatidylserine, and exosomes stimulated the interaction between Tim1 and Tim4. These results indicate that Tim4 and Tim1 are phosphatidylserine receptors for the engulfment of apoptotic cells, and may also be involved in intercellular signalling in which exosomes are involved.
    NATURE PUBLISHING GROUP, Nov. 2007, NATURE, 450(7168) (7168), 435 - 439, English
    [Refereed]
    Scientific journal

  • Tsukasa Baba, Masatoshi Kariya, Toshihiro Higuchi, Masaki Mandai, Noriomi Matsumura, Eiji Kondoh, Masanori Miyanishi, Ken Fukuhara, Kenji Takakura, Shingo Fujii
    Objective. Neuropilin-1 (NRP-1) is a receptor for both semaphorin and vascular endothelial growth factor and is up-regulated in a variety of human cancers. While there are some reports of NRP-1 expression in ovarian neoplasm, those results differ in pattern of its expression and its role in ovarian cancer is still unclear. We sought to investigate the expression pattern and role of NRP-1 in ovarian cancer. Methods. NRP-1 expression was analyzed with eighty-seven ovarian tissue samples by immunohistochemistry and four ovarian cell lines by quantitative RT-PCR and Western blotting. To detect its molecular role in ovarian cancer, WST-1 assay, invasion assay and soft agar assay were performed with or without NRP-1 suppression by the introduction of short hairpin RNAs. Results. NRP-1 expression was found to be enhanced in ovarian cancer compared with ovarian surface epithelium (OSE), benign adenoma and tumors of low malignant potential. In vitro, NRP-1 expression was augmented threefold during malignant transformation of OSE cells with oncogene ras, suggesting an association between NRP-1 and oncogenesis. Suppression of NRP-1 reduced cell proliferation in a dense state, indicating that persistently high expression of NRP-1 in ovarian cancer enhances proliferation through evasion of contact inhibition. Suppression of NRP-1 also decreased cell growth in soft agar and invasion to the extracellular matrix in vitro. Conclusions. These results suggest that NRP-1 is not only associated with oncogenesis, but also with ovarian cancer malignancy, and this molecule is a targeting candidate for the treatment of ovarian malignancies. (c) 2007 Elsevier Inc. All rights reserved.
    ACADEMIC PRESS INC ELSEVIER SCIENCE, Jun. 2007, GYNECOLOGIC ONCOLOGY, 105(3) (3), 703 - 711, English
    [Refereed]
    Scientific journal

  • Immortalized ovarian surface epithelial cells acquire tumorigenicity by acrogranin gene overexpression
    Masanori Miyanishi, Masaki Mandai, Noriomi Matsumura, Ken Yamaguchi, Junzo Hamanishi, Toshihiro Higuchi, Kenji Takakura, Shingo Fujii
    Malignant transformation is caused by multi-step genetic mutations, and growth factors are believed to play important roles in developing and maintaining malignant phenotype. However, there is no direct evidence that a specific growth factor contributes to malignant transformation of phenotypically normal cells. In order to assess the function of Acrogranin (also known as granulin epithelial precursor; GEP) in ovarian carcinogenesis, ovarian surface epithelial (OSE) cells, which are supposed to be the origin of primary ovarian epithelial cancer, were transfected with combined genes of hTERT, SV40 LT, and Acrogranin. Introduction of hTERT and SV40 LT was sufficient for immortalizing OSE cells but not enough for tumor formation in nude mice. In contrast, transfection and overexpression of Acrogranin in immortalized OSE cells showed augmented clonogenicity in soft agar and obvious tumorigenicity in nude mice. This is the first study showing evidence that a specific growth factor plays a direct role in malignant transformation in ovarian cancer development.
    PROFESSOR D A SPANDIDOS, Feb. 2007, ONCOLOGY REPORTS, 17(2) (2), 329 - 333, English
    [Refereed]
    Scientific journal

  • N Matsumura, M Mandai, M Miyanishi, K Fukuhara, T Baba, T Higuchi, M Kariya, K Takakura, S Fujii
    To identify potential oncogenes that contribute to the development of uterine leiomyosarcoma, we conducted a cDNA microarray analysis between normal uterine smooth muscle and uterine leiomyosarcoma. We found that acrogranin (also named PCDGF or progranulin) is overexpressed in uterine leiomyosarcoma. With immunohistochemical staining of 12 leiomyosarcoma cases, we verified acrogranin expression in tumor cells. Furthermore, the intensity of acrogranin expression correlated with high histologic grade and poor prognosis. To directly analyze the oncogenic properties of acrogranin, we established an immortalized uterine smooth muscle cell line by transfection of human telomerase reverse transcriptase into primary culture. This cell line retained the original characteristics of uterine smooth muscle cells, including spindle-shaped extension as well as expression of vimentin, estrogen receptor a, progesterone receptor, and a smooth muscle actin. Transfection of acrogranin into the immortalized uterine smooth muscle cells resulted in colony formation in soft agar, but the diameter of the colonies did not exceed 100 mu m. Transfection of both acrogranin and SV40 early region (SV40ER) into the immortalized uterine smooth muscle cells resulted in an increased number of colonies and increased colony size in soft agar versus transfection of SV40ER alone. We show that only immortalized uterine smooth muscle cells expressing both acrogranin and SV40ER are capable of tumor formation in nude mice. Thus, acrogranin is overexpressed in uterine leiomyosarcoma cells, particularly in high-grade cases, and forced expression of acrogranin in immortalized uterine smooth muscle cells contributes to malignant transformation, which suggest that acrogranin plays an important role in the pathogenesis of uterine leiomyosarcoma.
    AMER ASSOC CANCER RESEARCH, Mar. 2006, CLINICAL CANCER RESEARCH, 12(5) (5), 1402 - 1411, English
    [Refereed]
    Scientific journal

■ MISC
  • 多層性解析によるヒト造血幹細胞単離法の最適化
    宮西正憲, 宮西正憲, 長坂明臣, 酒巻太郎, 西克幸, 塚本成幸, 定岡恵, 山本暢之, 井上翔太郎, MY An Le
    2024, 日本再生医療学会総会(Web), 23rd

  • AI技術を用いたMDS患者骨髄細胞の解析
    増田健太, 中西加代子, 岩崎惇, 諫田淳也, 宮塚功, 宮西正憲, 高折晃史
    2024, 日本検査血液学会雑誌, 25

  • Refractory Evans syndrome after allo-HSCT in a patient with chronic granulomatous disease
    植村優, 長谷川大一郎, 真鍋修司, 田中祐介, 西尾周朗, 堀川翔伍, 秋定直宏, 兵頭さやか, 神前愛子, 斎藤敦郎, 岸本健治, 石田敏章, 森健, 井上翔太郎, 宮西正憲, 小阪嘉之
    2024, 日本造血・免疫細胞療法学会総会プログラム・抄録集, 46th

  • 深層学習を用いたコロニー形成ユニット(CFU)アッセイの自動化
    中田光隆, TASAVAT Trisitichoke, 岡芳樹, 伊藤誉子, 稲垣翼, 陳静, 中原菜摘, 平木友理, 野田修志, 宮西正憲, 宮西正憲, 竹谷誠
    2023, 日本再生医療学会総会(Web), 22nd

  • 多様性が求められる未来のARTについて 産婦人科出身造血幹細胞研究者が想造する未来医療
    宮西 正憲
    (一社)日本IVF学会, Sep. 2022, 日本IVF学会誌, 25(2) (2), 42 - 42, Japanese

  • 小児悪性脳腫瘍の発症・進行メカニズムに関連した単球・マクロファージ系血細胞の多様性に関する基礎的研究
    長谷川 大一郎, 田村 彰広, 宮西 正憲, 小阪 嘉之
    (一社)兵庫県医師会, Mar. 2022, 兵庫県医師会医学雑誌, 64(2) (2), 35 - 35, Japanese

  • 診断時単球絶対数とリンパ球絶対数の乗算低値は神経芽腫の予後不良に相関する(Low multiplication value of monocyte and lymphocyte count may be associated with poor prognosis in neuroblastoma)
    田村 彰広, 井上 翔太郎, 森 健, 中村 さやか, 齋藤 敦郎, 神前 愛子, 石田 敏章, 長谷川 大一郎, 小阪 嘉之, 宮西 正憲
    (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 230 - 230, English

  • ヒト造血幹細胞機能維持細胞増幅培養液の開発
    森田 寛之, 塚本 成幸, 宮西 正憲, 竹谷 誠
    (一社)日本組織培養学会, Aug. 2021, 組織培養研究, 39(1) (1), 93 - 93, Japanese

  • Establishment of a Predictive Model for GRFS after Allo-HSCT using Ensemble Learning
    岩崎惇, 岩崎惇, 諫田淳也, 諫田淳也, 新井康之, 新井康之, 近藤忠一, 近藤忠一, 石川隆之, 石川隆之, 上田恭典, 上田恭典, 今田和典, 今田和典, 赤坂尚司, 赤坂尚司, 米澤昭仁, 米澤昭仁, 野吾和宏, 野吾和宏, 直川匡晴, 直川匡晴, 安齋尚之, 安齋尚之, 森口寿徳, 森口寿徳, 北野俊行, 北野俊行, 伊藤満, 伊藤満, 有馬靖佳, 有馬靖佳, 竹岡友晴, 竹岡友晴, 渡邊光正, 渡邊光正, 平田大二, 平田大二, 浅越康助, 浅越康助, 宮西正憲, 宮塚功, AN Le My, 高折晃史, 高折晃史
    2021, 日本造血細胞移植学会総会プログラム・抄録集, 43rd

  • Development of proliferation and maintenance medium for human hematopoietic stem cells
    森田寛之, 塚本成幸, 宮西正憲, 竹谷誠
    2021, 組織培養研究(Web), 39(1) (1)

  • The cell fate of HSCs is regulated flexibly by hematopoietic stress
    酒巻太郎, 西克幸, 西克幸, 定岡恵, 藤井桃, 宮西正憲
    2021, 日本血液学会学術集会抄録(Web), 83rd

  • Alteration of the short/long-term hematopoietic stem cell ratio causes lineage-biased hematopoiesis
    西克幸, 西克幸, 酒巻太郎, 酒巻太郎, KAO Kevin, 定岡恵, 藤井桃, 高折晃史, 宮西正憲
    2021, 日本血液学会学術集会抄録(Web), 83rd

  • Nanoimprint lithographyと完全溶融式射出成形機を用いた新しい成形加工技術の開発
    高橋泰輔, 高橋泰輔, 土田新, 新宅博文, 宮西正憲, 須藤詩乃, 田口瑠南, 海邊政哉, 安田玲子, 黒澤修, 小此木孝仁, 西村文仁
    2021, 化学とマイクロ・ナノシステム学会研究会講演要旨集(CD-ROM), 44th

  • 希少細胞集団をターゲットにした高感度ChIP-Seq解析法の開発
    宮西正憲
    2020, ライフサイエンス振興財団助成成果報告書, 2019

  • C/EBPβ依存的非古典的単球の制御による新規小児がん治療法開発
    田村 彰広, 宮西 正憲
    [東京] : 小児医学研究振興財団, 2020, 公益財団法人小児医学研究振興財団研究報告書, 12 - 14, Japanese

  • 酒巻 太郎, 宮西 正憲
    造血幹細胞は自己複製能と多分化能を有する血液幹細胞と定義され,造血幹細胞移植成否の鍵を握る。過去60年にわたる造血幹細胞移植医療および幹細胞生物学における解析手法,技術の進歩とともに造血システムの理解は格段に深まってきた。しかし,造血幹細胞の本質である自己複製能や多分化能の分子メカニズムに関しては,ほとんど解明されていない。その理由の一つとして,骨髄内にわずかに含まれる造血幹細胞,中でも生涯にわたり自己複製能を有する長期造血幹細胞の同定,純化がこれまで成し遂げられなかったことが挙げられる。特に移植医療の現場においては,移植後長期にわたり造血能が維持されることは極めて重要であり,この細胞分画が臨床的にも科学的にも重要であることが理解できる。本稿では,造血幹細胞の同定,純化の歴史を紹介しつつ,特に長期造血幹細胞に関する臨床的,科学的意義,および最新の研究成果について述べたい。(著者抄録)
    (一社)日本血液学会-東京事務局, Sep. 2019, 臨床血液, 60(9) (9), 1056 - 1062, Japanese

  • 造血幹細胞のホーミングおよび分化におけるB4Galt1の役割
    山下莉映子, 山下莉映子, 成瀬智恵, 杉原一司, 金成香奈子, 高垣聡一郎, 宮西正憲, 岡昌吾, 浅野雅秀
    2019, 日本実験動物学会総会講演要旨集(Web), 66th

  • P1-118 上皮性卵巣癌におけるtrophininの発現意義(Group 16 卵巣腫瘍I,一般演題,講演要旨,第58回日本産科婦人科学会学術講演会)
    馬場,長, 刈谷,方俊, 宮西,正憲, 山田,重人, 松村,謙臣, 鈴木,彩子, 八木,治彦, 福原,健, 万代,昌紀, 樋口,壽宏, 高倉,賢二, 藤井,信吾
    日本産科婦人科学会, 01 Feb. 2006, 日本産科婦人科學會雜誌, 58(2) (2), 410, Japanese

  • 上皮性卵巣癌におけるtrophininの発現意義
    馬場 長, 刈谷 方俊, 宮西 正憲, 山田 重人, 松村 謙臣, 鈴木 彩子, 八木 治彦, 福原 健, 万代 昌紀, 樋口 壽宏, 高倉 賢二, 藤井 信吾
    (公社)日本産科婦人科学会, Feb. 2006, 日本産科婦人科学会雑誌, 58(2) (2), 410 - 410, Japanese

  • リンパ球と共培養することで, 細胞障害性T細胞の活性を高めるフィーダー細胞の作成(悪性腫瘍全般I, 第57回日本産科婦人科学会学術講演会)
    宮西,正憲, 松村,謙臣, 万代,昌紀, 馬場,長, 近藤,英治, 門間,千佳, 堀内,由佳, 福原,健, 樋口,壽宏, 刈谷,方俊, 高倉,賢二, 藤井,信吾
    日本産科婦人科学会, 01 Feb. 2005, 日本産科婦人科學會雜誌, 57(2) (2), 469, Japanese

  • hTERTとSV40LT抗原によって不死化した卵巣表層上皮細胞はAcrograninの遺伝子導入によって足場非依存性増殖が促進される
    万代 昌紀, 松村 謙臣, 宮西 正憲, 近藤 英治, 山田 重人, 志馬 裕明, 金森 崇修, 福原 健, 樋口 壽宏, 刈谷 方俊, 高倉 賢二, 藤井 信吾
    (公社)日本産科婦人科学会, Feb. 2005, 日本産科婦人科学会雑誌, 57(2) (2), 454 - 454, Japanese

  • 子宮平滑筋肉腫におけるAcrogranin過剰発現と組織学的悪性度との相関
    樋口 壽宏, 松村 謙臣, 万代 昌紀, 宮西 正憲, 馬場 長, 山田 重人, 堀内 由佳, 門間 千佳, 福原 健, 刈谷 方俊, 高倉 賢二, 藤井 信吾
    (公社)日本産科婦人科学会, Feb. 2005, 日本産科婦人科学会雑誌, 57(2) (2), 610 - 610, Japanese

  • 細胞障害性T細胞を効率的に活性化する樹状細胞を作成するためのFLT3 Ligand発現フィーダー細胞の作成
    松村 謙臣, 万代 昌紀, 宮西 正憲, 佐藤 寛, 山田 重人, 堀内 由佳, 金森 崇修, 福原 健, 樋口 壽宏, 刈谷 方俊, 高倉 賢二, 藤井 信吾
    (公社)日本産科婦人科学会, Feb. 2005, 日本産科婦人科学会雑誌, 57(2) (2), 469 - 469, Japanese

  • 平野 剛, 永野 忠義, 宮西 正憲, 榊原 敦子, 高橋 秀元, 岡垣 篤彦, 伴 千秋
    上皮性卵巣癌167例のうち,リンパ節郭清を107例に施行した.pT3症例でも65例中25例に施行し,その48%にリンパ節転移を認めた.FIGO進行期別の5年生存率は,III期では38%と不良であった.pT1症例とpT3症例を比較するとN1,N0,Nxで有意差はなかったが,pT1症例は5年を越えるとN1症例に死亡が増え,殆どが多発リンパ節転移例であった.pT3症例のうちM1を除く62例では,初回手術がoptimal手術となったのは17例で,再手術を含めると32例であった.suboptimal手術に終わった明細胞癌は化学療法に抵抗し,再手術例はなかった.手術完遂度別の5年生存率は,optimal手術例が42%,suboptimal手術例が26%と差があったが,長期追跡では予後の差はなかった.なおpT3症例において,リンパ節転移の有無で5年生存率を検討したが,有意差は認めず,化学療法の種類でも有意差はなかった
    「産婦人科の進歩」編集室, Aug. 2004, 産婦人科の進歩, 56(3) (3), 332 - 335, Japanese

  • 下垂体腺腫により惹起された両側多嚢胞性卵巣腫瘤の1例
    今岡 いずみ, 和田 昭彦, 松尾 導昌, 宮西 正憲, 吉田 益美, 欅 篤, 鍋島 祥男
    バイエル薬品(株), Apr. 2004, 日独医報, 49(1) (1), 147 - 147, Japanese

  • 腹水細胞診陽性の子宮体癌をいかに取り扱うか
    高橋 秀元, 永野 忠義, 宮西 正憲, 榊原 敦子, 平野 剛, 岡垣 篤彦, 伴 千秋
    「産婦人科の進歩」編集室, Apr. 2004, 産婦人科の進歩, 56(2) (2), 237 - 237, Japanese

  • 4年間の経過観察後に手術に至った子宮平滑筋肉腫の1例
    永野 忠義, 宮西 正憲, 榊原 敦子, 高橋 秀元, 平野 剛, 岡垣 篤彦, 伴 千秋, 真能 正幸, 高田 賀章
    「産婦人科の進歩」編集室, Apr. 2004, 産婦人科の進歩, 56(2) (2), 259 - 259, Japanese

  • 宮西 正憲
    (公社)日本産科婦人科学会, Feb. 2004, 日本産科婦人科学会雑誌, 56(2) (2), 575 - 575, Japanese

  • 宮西 正憲, 荒川 奈央子, 榊原 敦子, 高橋 秀元, 平野 剛, 岡垣 篤彦, 永野 忠義, 伴 千秋, 鈴木 暸
    「産婦人科の進歩」編集室, Nov. 2003, 産婦人科の進歩, 55(4) (4), 499 - 499, Japanese

  • 難治性卵巣癌に対する取り組み リンパ節転移症例を中心に
    平野 剛, 永野 忠義, 荒川 奈央子, 宮西 正憲, 榊原 敦子, 高橋 秀元, 岡垣 篤彦, 伴 千秋, 鈴木 暸
    「産婦人科の進歩」編集室, Nov. 2003, 産婦人科の進歩, 55(4) (4), 526 - 526, Japanese

  • 子宮体部類内膜腺癌術後早期に腹腔内に漿液性腺癌を発症した症例
    荒川 奈央子, 永野 忠義, 宮西 正憲, 榊原 敦子, 高橋 秀元, 平野 剛, 伴 千秋, 鈴木 暸, 河原 邦光, 倉田 明彦
    (公社)日本婦人科腫瘍学会, Jun. 2003, 日本婦人科腫瘍学会雑誌, 21(3) (3), 238 - 238, Japanese

  • 宮西 正憲, 中村 郁, 野口 明子, 南野 英隆, 林 道治, 吉田 益美
    「産婦人科の進歩」編集室, Nov. 2002, 産婦人科の進歩, 54(6) (6), 518 - 518, Japanese

  • 野口 明子, 中村 郁, 宮西 正憲, 南野 英隆, 林 道治, 吉田 益美
    「産婦人科の進歩」編集室, Nov. 2002, 産婦人科の進歩, 54(6) (6), 527 - 527, Japanese

  • 中村 郁, 宮西 正憲, 野口 明子, 南野 英隆, 林 道治, 吉田 益美
    「産婦人科の進歩」編集室, Nov. 2002, 産婦人科の進歩, 54(6) (6), 536 - 536, Japanese

  • 宮西 正憲, 中村 郁, 野口 明子, 南野 英隆, 林 道治, 吉田 益美, 今岡 いずみ, 小橋 陽一郎
    「産婦人科の進歩」編集室, May 2002, 産婦人科の進歩, 54(3) (3), 268 - 268, Japanese

  • 下垂体腺腫による高プロラクチン血症がhyperreactio luteinalis-like patternを惹起したと考えられる両側多発性卵巣嚢腫の1例
    宮西正憲, 今岡いずみ, 中村郁, 野口明子, 南野英隆, 林道治, 吉田益美, 和田昭彦, 松尾導昌
    2002, Abstracts. Annual Symposium. Japanese Society for the Advancement of Women’s Imaging, 3rd (Web)

  • 吉田 益美, 宮西 正憲, 野口 明子, 森田 康史, 南野 英隆, 林 道治, 中村 道三, 今岡 いずみ, 弓場 吉哲
    「産婦人科の進歩」編集室, Nov. 2001, 産婦人科の進歩, 53(6) (6), 560 - 560, Japanese

  • 住友 理浩, 樋口 壽宏, 加藤 倫隆, 宮西 正憲, 吉岡 弓子, 万代 昌紀, 北 正人, 刈谷 方俊, 藤井 信吾
    「産婦人科の進歩」編集室, May 2000, 産婦人科の進歩, 52(3) (3), 600 - 600, Japanese

  • 宮西 正憲, 樋口 壽宏, 万代 昌紀, 姜 賢淑, 野口 明子, 住友 理浩, 刈谷 方俊, 藤井 信吾, 中本 裕士
    「産婦人科の進歩」編集室, Nov. 1999, 産婦人科の進歩, 51(6) (6), 641 - 641, Japanese

■ Research Themes
  • 宮西 正憲
    科学技術振興機構, 戦略的な研究開発の推進 創発的研究支援事業, 神戸大学, 2023 - 2029, Principal investigator
    造血幹細胞を用いた細胞・再生医療は、白血病などの悪性の血液疾患以外にも、遺伝子改変技術等を組み合わせることで、将来的には様々な難治性疾患を根治しうることが期待されています。その一方で、造血幹細胞が生体内にごく僅かしか存在せず細胞の調整そのものが容易でないことが、これら夢の技術開発の大きな障害となっています。そこで本研究では、これらの医療技術開発に革新をもたらす体外細胞増幅技術の開発を目指します。

  • 造血系恒常性の維持から破綻に至るメカニズムの解明
    宮西 正憲
    日本学術振興会, 科学研究費助成事業, 基盤研究(B), 神戸大学, 01 Apr. 2025 - 31 Mar. 2028

  • Elucidation of the mechanism of rituximab-induced long-term remission in childhood nephrotic syndrome
    飯島 一誠, 堀之内 智子, 野津 寛大, 宮西 正憲
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2023 - 31 Mar. 2026

  • Elucidation of the mechanism of rituximab-induced long-term remission in childhood nephrotic syndrome
    飯島 一誠, 堀之内 智子, 野津 寛大, 宮西 正憲
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2023 - 31 Mar. 2026

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