2013 Fiscal Year Research-status Report
Project/Area Number |
25461216
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Research Institution | Nagoya University |
Principal Investigator |
丸山 彰一 名古屋大学, 医学(系)研究科(研究院), 准教授 (10362253)
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Co-Investigator(Kenkyū-buntansha) |
秋山 真一 名古屋大学, 医学(系)研究科(研究院), 特任講師 (20500010)
坪井 直毅 名古屋大学, 医学部附属病院, 講師 (50566958)
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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Project Period (FY) |
2013-04-01 – 2016-03-31
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Keywords | 間葉系幹細胞 / 脂肪 / 低血清 / mTOR |
Research Abstract |
申請者らは脂肪由来間葉系幹細胞(ASC)に着目し血清培養法を開発した。これまでに低血清培養脂肪由来間葉系幹細胞(LASC)が骨髄由来間葉系幹細胞と比較して、強い再生促進作用と免疫抑制作用を有することを見出し、その効果を各種動物実験で実証してきた。しかし、その作用機序には依然不明な点が多い。細胞治療を普及させるためには、動物由来物質の排除つまり無血清培養の開発が必要である。本研究課題は、1.飢餓状態で亢進するオートファジーとLASC の免疫抑制作用との関連を明らかにすること、2.LASC と免疫細胞との間の情報伝達機構を明らかにすること、そしてその知見に基づき3.高機能を維持したASC の無血清培養法を開発することを目的とした。 まず、オートファジー(自食作用)に着目して検討を行った。オートファジーは飢餓状態で亢進する現象で、細胞内浄化作用・老化抑制などに作用する。LASCではHASCと比較してオートファジーが亢進していることを確認した。 続いて、LASCのオートファジーをさらに亢進させる方法を模索した。低血糖培養液使用、あるいはmTOR阻害薬であるラパマイシンを用いてLASCに刺激を与えたが、オートファジーは有意に変化しなかった。さらに、HGFをはじめとする成長因子も変化しなかった。 そこで、低血清培養の後に無血清培養を行ったところ、HGFの分泌が亢進していた。免疫抑制能に関しては、現在こうして得られたLASCを中心に、従来のLASC、HASCとの比較を進めている。さらに、その違いにおける分子機序を明らかにするために、蛋白アレイを用いた網羅的解析も進めている。
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Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
ラパマイシンにより、高機能化LASCが作成させるという仮説を持って、本研究を開始したが、当初予想された結果は得られず、そのことを確認するための実験に多くの時間を要した。
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Strategy for Future Research Activity |
ラパマイシン刺激はあきらめ、LASCを一旦無血清にして培養する新しい手法の検討を進める。高機能化LASCが得られたら、成長因子分泌能や免疫抑制能について、従来のLASCやHASCあるいは骨髄由来MSCと比較する予定である。
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Research Products
(67 results)
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[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] 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.
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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.
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Journal Title
Am J Kidney Dis.
Volume: 61(2)
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.
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Journal Title
J Am Soc Nephrol
Volume: 24(4)
Pages: 587-603
DOI
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] TGF-β1 Promotes Lymphangiogenesis during Peritoneal Fibrosis.2013
Author(s)
Kinashi H, Ito Y, Mizuno M, Suzuki Y, Terabayashi T, Nagura F, Hattori R, Matsukawa Y, Mizuno T, Noda Y, Nishimura H, Nishio R, Maruyama S, Imai E, Matsuo S, Takei Y.
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Journal Title
J Am Soc Nephrol
Volume: 24(10)
Pages: 1627-42
DOI
Peer Reviewed
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[Journal Article] Geriatric nutritional risk index accurately predicts cardiovascular mortality in incident hemodialysis patients.2013
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: S0914-5087(13)
Pages: 00352-3
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(東京都港区)
Year and Date
20140514-20140517
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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] 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] CD147 Ameliorates Lupus Nephritis through the Regulation of Helper T Cell 17 Differentiation.2013
Author(s)
Kayaho Maeda, MD, Tomoki Kosugi, MD, PhD, Waichi Sato, MD, PhD, Hiroshi Kojima, MD, Yuka Sato, MD, Mayuko Maeda, MD, 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] 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)
Hiroshi Kojima, MD, Tomoki Kosugi, MD, PhD, Mayuko Maeda, MD, Kayaho Maeda, MD, Yuka Sato, MD, Hiroki Hayashi, MD, Waichi Sato, MD, PhD, 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] Resistance to Immunosuppressive Therapy in Patients with Primary Nephrotic Syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS)2013
Author(s)
Ryohei Yamamoto, MD, PhD, Shoichi Maruyama, MD, Hitoshi Yokoyama, MD, PhD, Seiichi Matsuo, MD, Enyu Imai, MD, PhD
Organizer
Kidney Week 2013
Place of Presentation
Atlanta(USA)
Year and Date
20131105-20131110
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[Presentation] Serum-starved adipose-derived stromal cells ameliorate rat crescentic glomerulonephritis by promoting immunoregulatory macrophages.2013
Author(s)
Kazuhiro Furuhashi, Naotake Tsuboi, Asuka Shimizu, Yiqin Shi, Hangsoo Kim, Takayuki Katsuno, Yosuke Saka, Takenori Ozaki, Waichi Sato, Enyu Imai, Seiichi Matsuo, Shoichi Maruyama
Organizer
ISSCR(International Society for Stem Cell Research) 11th Annual Meeting
Place of Presentation
Boston(USA)
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] DESMOPRESSIN IS EFFECTIVE IN PREVENTING OVERCORRECTION OF HYPONATREMIA.2013
Author(s)
Takaya Ozeki, Hideaki Shimizu, Akihiro Ryuge, Yukako Ooyama, Takahiro Imaizumi, Rui Kawato, Takuya Hamada, Atsushi Nomura, Tatsuhito Tomino, Yoshiro Fujita, Shoichi Maruyama.
Organizer
The World Congress of Nephrology 2013
Place of Presentation
香港(中国)
Year and Date
20130531-20130604
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