2013 Fiscal Year Research-status Report
抗体結合型バイオナノカプセルを応用した炎症白血球特異的新規腎障害治療法の開発
Project/Area Number |
25670408
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Research Institution | Nagoya University |
Principal Investigator |
松尾 清一 名古屋大学, 医学(系)研究科(研究院), 教授 (70190410)
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Co-Investigator(Kenkyū-buntansha) |
坪井 直毅 名古屋大学, 医学部附属病院, 講師 (50566958)
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Keywords | マクロファージ / バイオナノカプセル / 腎虚血再還流障害 / ドラッグデリバリー |
Research Abstract |
慢性腎炎や糖尿病性腎症など主な慢性腎臓病(CKD)の発症・進展過程に共通する最も重要な機序に炎症があげられるが、従来の全身的免疫抑制療法では効果に限界があり、また重篤な副作用は極めて深刻な治療中断規定因子となっている。今回の研究ではバイオナノカプセル(BNC)を応用したドラッグデリバリーシステム(DDS)により、CKDにおいて腎組織障害の中心的役割を担う好中球・マクロファージ(Mφ)を選択的かつ炎症部位特異的に機能抑制することで、抗炎症・免疫抑制効果と副作用の軽減を両立させた革新的な治療法開発を目指した。 本年度の申請者の研究実績として、 1.Cy3蛍光標識BNC-αIgG作成とin vitro局在解析:Cy3標識したZZ-tag提示型BNCに、モノクローナル抗CD62E抗体あるいは抗CD11b抗体を結合させ作成した。マウス血管内皮細胞株(MBEC4)、マクロファージ細胞株(RAW264.7)にCy3で蛍光標識したBNC-αCD62EmIgG、BNC-αCD11bmIgGをそれぞれ添加し、BNCの局在を共焦点レーザー顕微鏡で確認した。 2.全身投与BNC-αIgGのin vivo追跡:蛍光標識した抗E-selectinあるいは抗CD11b抗体接合BNCをマウスに経静脈投与したところIRI作成腎皮髄境界部優位なCy3陽性細胞を認めたが、非虚血腎には所見をみなかった。また肝臓・脾臓、及び心臓の一部にBNCの取り込みを認めたが、肺には認めなかった。
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
本研究では当初提案した好中球特異的ヒト化FcγRトランスジェニックマウス(hFcγRTgマウス)の入手が遅れたため、まずは野生型C57BL/6マウスを用い、好中球、マクロファージ特異的なCD11b、あるいは内皮細胞に特異的なCD62Eに対する抗体をBNCに結合させたバイオナノカプセルをそれぞれ作成した。実験1.において両バイオナノカプセルのマクロファージ細胞株、内皮細胞株への取り込みが有意に認められ、実験2.でBNCの集積が虚血腎間質に認められ、マクロファージや内皮細胞特異的にBNCがdeliveryされた可能性があることが示唆された。また、実験3.においてBNCに結合したCD62E抗体やCD11b抗体そのものによる虚血再還流モデルの腎機能障害軽減は認めず、リポソーム内に含有させた薬剤の効果を比較できると判断した。しかしながら、実験4.において、GFPプラスミド封入リポソーム-BNCをIn vivo及びIn vitroで投与した際にはGFPの発現を認めなかった。またIn vivoにおいても、実験2.の結果と異なり、リポソーム封入Cy3標識BNCの虚血腎への集積所見が認められなかったため、リポソーム封入によりBNCのサイズが変化し到達効率が低下した可能性を示唆する結果となった。
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Strategy for Future Research Activity |
次年度は、治療薬剤非封入下でのBNC-αIgG腎毒性と治療効果の判定、疾患治療遺伝子封入BNC-αIgGを作成し、in vitro, in vivoで細胞あるいは組織での発現確認を行う予定である。また糸球体腎炎を惹起するマウス抗基底膜抗体を昨今当研究室独自に作成したため、虚血再還流障害以外の腎障害に対してもBNCの到達効率を評価したいと考えている。
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[Journal Article] Geriatric nutritional risk index accurately predicts cardiovascular mortality in incident hemodialysis patients.2014
Author(s)
Takahashi H, Ito Y, Ishii H, Aoyama T, Kamoi D, Kasuga H, Yasuda K, Maruyama S, Matsuo S, Murohara T, Yuzawa Y.
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Journal Title
J Cardiol
Volume: 64(1)
Pages: 32-6
DOI
Peer Reviewed
-
[Journal Article] Rat adipose tissue-derived stem cells attenuate peritoneal injuries in rat zymosan-induced peritonitis accompanied by complement activation.2014
Author(s)
Kim H, Mizuno M, Furuhashi K, Katsuno T, Ozaki T, Yasuda K, Tsuboi N, Sato W, Suzuki Y, Matsuo S, Ito Y, Maruyama S.
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Journal Title
Cytotherapy.
Volume: 16(3)
Pages: 357-68
DOI
Peer Reviewed
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[Journal Article] Japan Renal Biopsy Registry and Japan Kidney Disease Registry: Committee Report for 2009 and 2010.2013
Author(s)
Sugiyama H, Yokoyama H, Sato H, Saito T, Kohda Y, Nishi S, Tsuruya K, Kiyomoto H, Iida H, Sasaki T, Higuchi M, Hattori M, Oka K, Kagami S, Kawamura T, Takeda T, Hataya H, Fukasawa Y, Fukatsu A, Morozumi K, Yoshikawa N, Shimizu A, Kitamura H, Yuzawa Y, Matsuo S, Kiyohara Y, Joh K, Nagata M, Taguchi T, Makino H
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Journal Title
Clin Exp Nephrol.
Volume: 17(2)
Pages: 155-73
DOI
Peer Reviewed
-
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[Journal Article] Deficiency of growth factor midkine exacerbates necrotizing glomerular injuries in progressive glomerulonephritis.2013
Author(s)
Kojima H, Kosugi T, Sato W, Sato Y, Maeda K, Kato N, Kato K, Inaba S, Ishimoto T, Tsuboi N, Matsuo S, Maruyama S, Yuzawa Y, Kadomatsu K.
-
Journal Title
Am J Pathol
Volume: 182(2)
Pages: 410-9
DOI
Peer Reviewed
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[Journal Article] Association of cardiac valvular calcifications and C-reactive protein with cardiovascular mortality in incident hemodialysis patients: a Japanese cohort study.2013
Author(s)
Takahashi H, Ishii H, Aoyama T, Kamoi D, Kasuga H, Ito Y, Yasuda K, Tanaka M, Yoshikawa D, Maruyama S, Matsuo S, Murohara T, Yuzawa Y.
-
Journal Title
Am J Kidney Dis
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Pages: 254-61
DOI
Peer Reviewed
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[Journal Article] Serum-Starved Adipose-Derived Stromal Cells Ameliorate Crescentic GN by Promoting Immunoregulatory Macrophages.2013
Author(s)
Furuhashi K, Tsuboi N, Shimizu A, Katsuno T, Kim H, Saka Y, Ozaki T, Sado Y, Imai E, Matsuo S, Maruyama S.
-
Journal Title
J Am Soc Nephrol.
Volume: 24(4)
Pages: 587-603
DOI
Peer Reviewed
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[Journal Article] Overestimation of the risk of progression to end-stage renal disease in the poor prognosis' group according to the 2002 Japanese histological classification for immunoglobulin A nephropathy.2013
Author(s)
Miyazaki Y, Kawamura T, Joh K, Okonogi H, Koike K, Utsunomiya Y, Ogura M, Matsushima M, Yoshimura M, Horikoshi S, Suzuki Y, Furusu A, Yasuda T, Shirai S, Shibata T, Endoh M, Hattori M, Akioka Y, Katafuti R, Hashiguchi A, Kimura K, Matsuo S, Tomino Y.
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Journal Title
Clin Exp Nephrol.
Volume: Epub
Pages: Epub
Peer Reviewed
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[Journal Article] Anti-C5a complementary peptide ameliorates acute peritoneal injuries induced by neutralization of Crry and CD59.2013
Author(s)
Mizuno T, Mizuno M, Imai M, Suzuki Y, Kushida M, Noda Y, Maruyama S, Okada H, Okada N, Matsuo S, Ito Y.
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Journal Title
Am J Physiol Renal Physiol.
Volume: 305(11)
Pages: F1603-16
DOI
Peer Reviewed
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[Journal Article] Significance of combined cyclosporine-prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial.2013
Author(s)
Saito T, Iwano M, Matsumoto K, Mitarai T, Yokoyama H, Yorioka N, Nishi S, Yoshimura A, Sato H, Ogahara S, Shuto H, Kataoka Y, Ueda S, Koyama A, Maruyama S, Nangaku M, Imai E, Matsuo S, Tomino Y; The Refractory Nephrotic Syndrome Study Group.
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Journal Title
Clin Exp Nephrol.
Volume: Epub
Pages: Epub
Peer Reviewed
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[Journal Article] CD147/basigin reflects renal dysfunction in patients with acute kidney injury.2013
Author(s)
Nagaya H, Kosugi T, Maeda-Hori M, Maeda K, Sato Y, Kojima H, Hayashi H, Kato N, Ishimoto T, Sato W, Yuzawa Y, Matsuo S, Kadomatsu K, Maruyama S.
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Journal Title
Clin Exp Nephrol.
Volume: Epub
Pages: Epub
Peer Reviewed
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[Journal Article] Long-Term Effects of Spironolactone in Peritoneal Dialysis Patients.2013
Author(s)
Ito Y, Mizuno M, Suzuki Y, Tamai H, Hiramatsu T, Ohashi H, Ito I, Kasuga H, Horie M, Maruyama S, Yuzawa Y, Matsubara T, Matsuo S; on behalf of the Nagoya Spiro Study Group.
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Journal Title
J Am Soc Nephrol.
Volume: Epub
Pages: Epub
Peer Reviewed
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[Presentation] Spironolactone improving intrarenal renin-angiotensin system activation in type 2diabetic nephropathy patients with overt albuminuria.2014
Author(s)
Sawako Kato, Shoichi Maruyama, Hirofumi Makino, Jun Wada, Takashi Uzu, Hisazumi Araki, Daisuke Koya, Keizo Kanasaki, Akira Nishiyama, Hiroyuki Kobori, Enyu Imai, Masahiko Ando, Yutaka Oiso, Seiichi Matsuo
Organizer
The 14th Asian Pacific Congress of Nephrology
Place of Presentation
SHINAGAWA PRINCE HOTEL(東京港区区)
Year and Date
20140514-20140517
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[Presentation] Lower Serum Albumin Level Is Associated with Higher Fractional Excretion of Creatinine.2013
Author(s)
Masaru Horio, MD, Enyu Imai, MD, PhD, Yoshinari Yasuda, MD, PhD, Tsuyoshi Watanabe, MD, Seiichi Matsuo, MD
Organizer
Kidney Week 2013
Place of Presentation
Atlanta,USA
Year and Date
20131105-20131110
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[Presentation] Spironolactone Prevents Cardiac Hypertrophy in Peritoneal Dialysis Patients without Significant Adverse Effects.2013
Author(s)
Yasuhiko Ito, MD, PhD, Masashi Mizuno, MD, PhD, Yasuhiro Suzuki, MD, Hirotake Kasuga, MD, PhD, Shoichi Maruyama, MD, Yukio Yuzawa, MD, Seiichi Matsuo, MD
Organizer
Kidney Week 2013
Place of Presentation
Atlanta,USA
Year and Date
20131105-20131110
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[Presentation] The Nationwide Retrospective Cohort Study in IgA Nephropathy in Japan.2013
Author(s)
Takashi Yasuda, MD, PhD, Yoshinari Yasuda, MD, PhD, Sachiko Ohde, Osamu Takahashi, MD, PhD, Tetsuya Kawamura, MD, PhD, Seiichi Matsuo, MD
Organizer
Kidney Week 2013
Place of Presentation
Atlanta,USA
Year and Date
20131105-20131110
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[Presentation] Adverse Events Associated with Immunosuppressive Therapy and Tonsillectomy in IgAN: The Nationwide Retrospective Cohort Study in IgAN in Japan.2013
Author(s)
Yoshinari Yasuda, MD, PhD, Takashi Yasuda, MD, PhD, Sachiko Ohde, Osamu Takahashi, MD, PhD, Tetsuya Kawamura, MD, PhD, Seiichi Matsuo, MD
Organizer
Kidney Week 2013
Place of Presentation
Atlanta,USA
Year and Date
20131105-20131110
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[Presentation] Neutrophil/Lymphocyte Ratio as a Predictor of Cardiovascular Events in Japanese Patients Starting Renal Replacement Therapy.2013
Author(s)
Sawako Kato, MD, PhD, Bengt Lindholm, MD, PhD, Yukio Yuzawa, MD, Seiichi Matsuo, MD, Shoichi Maruyama, MD
Organizer
Kidney Week 2013
Place of Presentation
Atlanta,USA
Year and Date
20131105-20131110
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[Presentation] Mac-1 Deficiency Protects Mouse from Pulmonary Hemorrhage, whereas Exacerbates Glomerulonephritis in Experimental Model of Systemic Lupus Erythematosus.2013
Author(s)
Yiqin Shi, Naotake Tsuboi, MD, PhD, Kazuhiro Furuhashi, MD, PhD, Shoichi Maruyama, MD, Seiichi Matsuo, MD
Organizer
Kidney Week 2013
Place of Presentation
Atlanta,USA
Year and Date
20131105-20131110
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[Presentation] Glycosylated Protein CD147 Reflects Renal Dysfunction in Patients with Acute Tubular Necrosis.2013
Author(s)
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Organizer
Kidney Week 2013
Place of Presentation
Atlanta,USA
Year and Date
20131105-20131110
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[Presentation] C-Reactive Protein Mediates the Association between Low Socioeconomic Status and Pulse Pressure in Japanese CKD Cohort (CKD-JAC).2013
Author(s)
Naohiko Fujii, MD, PhD, Takayuki Hamano, MD, PhD, Yoshitaka Isaka, MD, PhD, Tsuyoshi Watanabe, MD, Kosaku Nitta, MD, PhD, Tadao Akizawa, MD, Seiichi Matsuo, MD, Enyu Imai, MD, PhD, Hirofumi Makino, MD, PhD
Organizer
Kidney Week 2013
Place of Presentation
Atlanta,USA
Year and Date
20131105-20131110
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[Presentation] Resistance to Immunosuppressive Therapy in Patients with Primary Nephrotic Syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS)2013
Author(s)
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Organizer
Kidney Week 2013
Place of Presentation
Atlanta,USA
Year and Date
20131105-20131110
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[Presentation] Regional Differences in Chronic Kidney Disease Prevalence in Japan: A Japanese Nationwide Health-Check Study.2013
Author(s)
Yoshinari Yasuda, MD, PhD, Kiyoshi Shibata, PhD, Kunitoshi Iseki, MD, Toshiki Moriyama, MD, PhD, Kunihiro Yamagata, MD, PhD, Kazuhiko Tsuruya, MD, PhD, Hideaki Yoshida, MD, PhD, Shouichi Fujimoto, MD, Koichi Asahi, MD, PhD, Tsuyoshi Watanabe, MD, Seiichi Matsuo, MD
Organizer
Kidney Week 2013
Place of Presentation
Atlanta,USA
Year and Date
20131105-20131110
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[Presentation] The continuous erythropoietin receptor activator (C.E.R.A.) maintains renal anemia safely at extended administration intervals in CAPD patients.2013
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Organizer
6th International Society for Peritoneal Dialysis - Asia Pacific Chapter Meeting, ISPD-APCM
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Year and Date
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[Presentation] Serum-starved adipose-derived stromal cells ameliorate rat crescentic glomerulonephritis by promoting immunoregulatory macrophages.2013
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Organizer
ISSCR(International Society for Stem Cell Research) 11th Annual Meeting
Place of Presentation
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Year and Date
20130612-20130615
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[Presentation] BENEFICIAL EFFECT OF CONTINUOUS ERYTHROPOIETIN RECEPTOR ACTIVATOR (C.E.R.A.) IN CAPD PATIENTS.2013
Author(s)
Yasuhiro Suzuki, Yasuhiko Ito, Masashi Mizuno, Hideki Hiramatsu, Hiroshi Kinashi, Humiko Nagura, Takeshi Terabayashi, Yumi Sei, Takako Tomita, Shoichi Maruyama, Seiichi Matsuo.
Organizer
The World Congress of Nephrology 2013
Place of Presentation
香港(中国)
Year and Date
20130531-20130604
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[Presentation] LOW SERUM CULTURED ADIPOSE-DERIVED MESENCHIMAL STROMAL CELLS AMERIORATE RAT MODEL WITH UNILATERAL URETERAL OBSTRUCTION.2013
Author(s)
Tomoko Abe, Asuka Horinouchi, Hangsoo Kim, Kazuhiro Huruhashi, Shinichi Aiyama, Takayuki Katsuno, Kaoru Yasuda, Takinori Ozaki, Naotake Tsuboi, Seiichi Matsuo, Shouichi Maruyama.
Organizer
The World Congress of Nephrology 2013
Place of Presentation
香港(中国)
Year and Date
20130531-20130604
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[Presentation] THE SERUM BETA 2-MICROGLOBULIN LEVEL PREDICTS PATIENT SURVIVAL IN ASSOCIATION WITH THE RESIDUAL RENAL FUNCTION IN JAPANESE PATIENTS ON PERITONEAL DIALYSIS: A PROSPECTIVE MULTICENTER COHORT STUDY (PDR-CS) .2013
Author(s)
Hitoshi Sugiyama, Yasuhiko Ito, Kazuhiko Tsuruya, Hisako Yoshida, Hiroki Maruyama,Shin Goto, Tomoya Nishino, Masaaki Nakayama, Hidetomo Nakamoto, Hiroshi Morinaga, Seiichi Matsuo,Hirofumi Makino.
Organizer
The World Congress of Nephrology 2013
Place of Presentation
香港(中国)
Year and Date
20130531-20130604
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[Presentation] THE LOWER SOCIOECONOMIC STATUS DOES NOT REPRESENT THE WORSE PHOSPHATE STATUS IN JAPAN, UNLIKE IN THE UNITED STATES.2013
Author(s)
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Organizer
The World Congress of Nephrology 2013
Place of Presentation
香港(中国)
Year and Date
20130531-20130604
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