Elucidation of molecular mechanisms involved in the immunomodulatory function of newly developed adipose tissue derived mesenchymal stem cells

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659443
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Nagoya University
• Principal Investigator: MATSUO Seiichi 名古屋大学, 医学系研究科, 教授 (70190410)
• Co-Investigator(Kenkyū-buntansha): MARUYAMA Shoichi 名古屋大学, 医学(系)研究科(研究院), 准教授 (10362253) ; AKIYAMA Shinichi 名古屋大学, 医学(系)研究科(研究院), 特任講師 (20500010) ; OZAKI Takenori 名古屋大学, 医学部附属病院, 病院助教 (10452195)
• Project Period (FY): 2011 – 2012
• Keywords: 幹細胞 / 再生医療 / 免疫抑制

Research Abstract

We have proven that low serum cultured adipose derived mesenchymal stem cells (LASC) suppress T cell proliferation and induce polarization of macrophages into immunomodulatory M2 type, and that these effects of LASC were much stronger than high serum cultured adipose derived mesenchymal stem cells (HASC) or bone marrow derived mesenchymal stem cells (BM-MSC). Inthis study, we studied the mechanisms involved in the immunosuppressive functionof LASC by comparing with HASC or BM-MSC. We found by neutralization experiment and stimulation experiment that LASC derived PGE2 and IL-6 are necessary for the polarization of M2 macrophages, and that PGE2 function via EP4 receptor.

Research Products

• [Journal Article] Distribution of hydrogen sulfide (H(2)S)-producing enzymes and the roles of the H(2)S donor sodium hydrosulfide in diabetic nephropathy (2013)
  • Author(s): Yamamoto J, Sato W, Kosugi T, Yamamoto T, Kimura T, Taniguchi S, Kojima H, Maruyama S, Imai E, Matsuo S, Yuzawa Y, Niki I
  • Journal Title: Clin Exp Nephrol Volume: 17(1) Pages: 32-40
  • Peer Reviewed
• [Journal Article] Transforming growth factor- β induces vascular endothelial growth factor-C expression leading to lymphangiogenesis in rat unilateral ureteral obstruction (2012)
  • Author(s): Suzuki Y, Ito Y, Mizuno M, Kinashi H, Sawai A, Noda Y, Mizuno T, Shimizu H, Fujita Y, Matsui K, Maruyama S, Imai E, Matsuo S, Takei Y
  • Journal Title: Kidney Int Volume: 81(9) Pages: 865-79
  • Peer Reviewed
• [Journal Article] (2012)
  • Author(s): Glomerular hyperfiltration in prediabetes and prehypertension. Okada R, Yasuda Y, Tsushita K, Wakai K, Hamajima N, Matsuo S
  • Journal Title: Nephrol Dial Transplant Volume: 27(5) Pages: 1821-5
  • Peer Reviewed
• [Journal Article] Atelocollagen-mediated systemic delivery prevents immunostimulatory adverse effects of siRNA in mammals (2012)
  • Author(s): Inaba S, Nagahara S, Makita N, Tarumi Y, Ishimoto T, Matsuo S, Kadomatsu K, Takei Y.
  • Journal Title: Mol Ther Volume: 20(2) Pages: 356-66
  • Peer Reviewed
• [Journal Article] Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy (2012)
  • Author(s): Hirayama A, Nakashima E, Sugimoto M, Akiyama S, Sato W, Maruyama S, Matsuo S, Tomita M, Yuzawa Y, Soga T
  • Journal Title: Anal Bioanal Chem Volume: 404(10) Pages: 3101-9
  • Peer Reviewed
• [Journal Article] Combined Values of Serum Albumin, C-Reactive Protein and Body Mass Index at Dialysis Initiation Accurately Predicts Long-Term Mortality (2012)
  • Author(s): Takahashi R, Ito Y, Takahashi H, Ishii H, Kasuga H, Mizuno M, Suzuki Y, Yuzawa Y, Maruyama S, Murohara T, Imai E, Matsuo S
  • Journal Title: Am J Nephrol Volume: 36(2) Pages: 136-43
  • Peer Reviewed
• [Journal Article] Autologous cell therapy for cisplatin-induced acute kidney injury by using non-expanded adipose tissue-derived cells (2012)
  • Author(s): Yasuda K, Ozaki T, Saka Y, Yamamoto T, Gotoh M, Ito Y, Yuzawa Y, Matsuo s, Maruyama S
  • Journal Title: Cytotherapy Volume: 14(9) Pages: 1089-100
  • Peer Reviewed
• [Journal Article] Complete remission within 2 years predicts a good prognosis after methylprednisolone pulse therapy in patients with IgA nephropathy (2012)
  • Author(s): Tatematsu M, Yasuda Y, Morita Y, Sakamoto I, Kurata K, Naruse T, Yamamoto R, Tsuboi N, Sato W, Imai E, Matsuo s, Maruyama S
  • Journal Title: Clin Exp Nephrol Volume: 16(6) Pages: 883-91
  • Peer Reviewed
• [Journal Article] ANCA-associated systemic vasculitis in Japan: clinical features and prognostic changes (2012)
  • Author(s): Yamagata K, Usui J, Saito C, Yamaguchi N, Hirayama K, Mase K, Kobayashi M, Koyama A, Sugiyama H, Nitta K, Wada T, Muso E, Arimura Y, Makino H, Matsuo s
  • Journal Title: Clin Exp Nephrol Volume: 16(4) Pages: 580-8
  • Peer Reviewed
• [Journal Article] Atrial natriuretic peptide ameliorates peritoneal fibrosis in rat peritonitis model (2012)
  • Author(s): Kato H, Mizuno T, Mizuno M, Sawai A, Suzuki Y, Kinashi H, Nagura F, Maruyama S, Noda Y, Yamada K, Matsuo s, Ito Y
  • Journal Title: Nephrol Dial Transplant Volume: 27(2) Pages: 526-36
• [Journal Article] Adipose-derived stromal cells cultured in a low-serum medium, but not bone marrow-derived stromal cells, impede xenoantibody production (2011)
  • Author(s): Saka Y, Furuhashi K, Katsuno T, Kim H, Ozaki T, Iwasaki K, Haneda M, Sato W, Tsuboi N, Ito Y, Matsuo s, Kobayashi T, Maruyama S
  • Journal Title: Xenotransplantation Volume: 18(3) Pages: 196-208
  • Peer Reviewed
• [Journal Article] Specific collaboration between rat membrane complement regulators Crry and CD59 protects peritoneum from damage by autologous complement activation (2011)
  • Author(s): Mizuno T, Mizuno M, Morgan BP, Noda Y, Yamada K, Okada N, Yuzawa Y, Matsuo s, Ito Y
  • Journal Title: Nephrol Dial Transplant Volume: 26(6) Pages: 1821-30
  • Peer Reviewed
• [Journal Article] Management of anemia in chronic kidney disease patients: baseline findings from Chronic Kidney Disease Japan Cohort Study (2011)
  • Author(s): Akizawa T, Makino H, Matsuo s, Watanabe T, Imai E, Nitta K, Ohashi Y, Hishida A
  • Journal Title: Clin Exp Nephrol Volume: 15(2) Pages: 248-57
  • Peer Reviewed
• [Journal Article] Basigin/CD147 promotes renal fibrosis after unilateral ureteral obstruction (2011)
  • Author(s): Kato N, Kosugi T, Sato W, Ishimoto T, Kojima H, Sato Y, Sakamoto K, Maruyama S, Yuzawa Y, Matsuo s
  • Journal Title: Kadomatsu K. Am J Pathol Volume: 178(2) Pages: 572-9
  • Peer Reviewed
• [Journal Article] Analysis of glial cell line-derived neurotrophic factor-inducible zinc finger protein 1 expression in human diseased kidney (2011)
  • Author(s): Saito S, Murakumo Y, Tsuzuki T, Dambara A, Kato T, Enomoto A, Asai N, Maruyama S, Matsuo s, Takahashi M
  • Journal Title: Hum Pathol Volume: 42(6) Pages: 848-58
  • Peer Reviewed
• [Journal Article] Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin (2011)
  • Author(s): Kato K, Kosugi T, Sato W, Arata-Kawai H, Ozaki T, Tsuboi N, Ito I, Tawada H, Yuzawa Y, Matsuo s, Kadomatsu K, Maruyama S
  • Journal Title: Clin Exp Nephrol Volume: 15(3) Pages: 346-54
  • Peer Reviewed
• [Journal Article]
  • Author(s): Low serum cultured adipose tissue-derived stromal cells ameliorate acute kidney injury in rats. Katsuno T, Ozaki T, Saka Y, Furuhashi K, Kim H, Yasuda K, Yamamoto T, Sato W, Tsuboi N, Mizuno M, Ito Y, Imai E, Matsuo S, Maruyama S
  • Journal Title: Cell Transplant
  • Peer Reviewed
• [Presentation] Low Serum Cultured Adipose-Derived Mesenchymal Stromal Cells Ameliorate Rat Model with Zymosan Induced Severe Peritonitis (2012)
  • Author(s): Hangsoo Kim, Masashi Mizuno, Kazuhiro Furuhashi, Takayuki Katsuno, Takenori Ozaki, Kaoru Yasuda, Waichi Sato, Naotake Tsuboi, Yasuhiko Ito, Enyu Imai, Shoichi M aruyama Seiichi Matsuo
  • Organizer: 45rd Annual Meeting of The American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2012-11-03
• [Presentation] Lack of Basigin Exacerbates Lupus Nephritis in Experimental Lupus Model (2012)
  • Author(s): Kayaho Maeda, Tomoki Kosugi, Waichi Sato, Hiroshi Kojima, Yuka Sato, Hiroshi Nagaya, Mayuko Maeda, Tomohiro Masuda, Shoichi Maruyama Seiichi Matsuo
  • Organizer: 45rd Annual Meeting of The American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2012-11-02
• [Presentation] Serum Starved Adipose-Derived Stromal Cells Ameliorate Rat Crescentic Glomerulonephritis by Promoting the Generation of M2 Immunoregulatory Macrophages (2012)
  • Author(s): Kazuhiro Furuhashi, , Naotake Tsuboi, Hangsoo Kim, Takayuki Katsuno, Waichi Sato, Enyu Imai, PhD, Seiichi Matsuo Shoichi Maruyama
  • Organizer: 45rd Annual Meeting of The American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2012-11-02
• [Presentation] POTENTIAL OF ADIPOSE-DERIVED STEM CELLS FROM HUMAN/RAT/MOUSE AS A NEW TOOL FOR THE TREATMENT OF SYSTEMIC SCLEROSIS (2012)
  • Author(s): Maruyama Shoichi, Shimizu, Asuka, Furuhashi, Kazuhiro, Ozaki Takenori, Kim, Hang Su, Abe, Tomoko, Katsuno, Takayuki, Tsuboi, Naotake, Matsuo seiichi
  • Organizer: International Society for Stem Cell Research 10th Annual Meeting
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-13
• [Presentation] ナノチューブを介したオルガネラ交換-幹細胞治療の新たなメカニズム (2012)
  • Author(s): 安田香、丸山彰一、佐藤和一、坪井直毅、伊藤恭彦、今井圓裕、松尾清一
  • Organizer: 第55回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-01
• [Presentation] Mac-1 Deficiency Protects Mouse from Pulmonary Hemorrhage, Whereas Exacerbates Glomerulonephritis in Experimental Model of Systemic Lupus Erythematosus (2012)
  • Author(s): Shi Yiqin, Naotake Tsuboi, Kazuhiro Furuhashi, Asuka Shimizu, Hansu Kimu, Tanya Mayadas, Shoichi M aruyama Seiichi Matsuo
  • Organizer: The Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012(AP-VAS)
  • Place of Presentation: 東京コンファレンスセンター
  • Year and Date: 2012-03-29
• [Presentation] Low Serum Cultured Adipose-derived Mesenchymal Stem Cells Ameliorate Crescentic Glomerulonephritis by Functional Polarization of Macrophages into Immunoregulatory M2 Phenotype (2012)
  • Author(s): Kazuhiro Furuhashi, Naotake Tsuboi, Asuka Shimizu, Hangsoo Kim, Takayuki Katsuno, Yousuke Saka, Takenori Ozaki, Waichi Sato, Enyu Imai, Seiichi Matsuo,Shoichi Maruyama
  • Organizer: The Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012(AP-VAS)
  • Place of Presentation: 東京コンファレンスセンター
  • Year and Date: 2012-03-29
• [Presentation] Low Serum Cultured Adipose Derived Stem Cells Ameliorate Zymosan Induced Severe Rat Peritonitis Model (2011)
  • Author(s): Hangsoo Kim, Masashi Mizuno,Kazuhiro Furuhashi, Takayuki Katsuno, Kaoru Yasuda, Takenori Ozaki, Waichi Sato, Naotake Tsuboi, Yasuhiko Ito, Enyu Imai, Shoichi M aruyama Seiichi Matsuo
  • Organizer: 44rd Annual Meeting of The American Society of Nephrology
  • Place of Presentation: Philadelphia, PA
  • Year and Date: 2011-11-11
• [Presentation] Association of Adipokines with Cardiovascular Mortality in Patients on Hemodialysis (2011)
  • Author(s): Shoichi Maruyama, Kaoru Yasuda, Hirotake Kasuga, Yoshinari Yasuda, Tomoki Kosugi, Waichi Sato, Naotake Tsuboi, Yasuhiko Ito, Enyu Imai, Seiichi Matsuo
  • Organizer: 44rd Annual Meeting of The American Society of Nephrology
  • Place of Presentation: Philadelphia, PA
  • Year and Date: 2011-11-10
• [Presentation] Low Serum Cultured Adipose-Derived Mesenchymal Stem Cells, but Not Bone-Marrow Derived Mesenchymal Stem Cells, Ameliorate Rat Crescentic Glomerulonephritis by Functional Polarization of Macrophages into Immunoregulatory Phenotype (2011)
  • Author(s): Kazuhiro Furuhashi, Naotake Tsuboi, PhD, Hangsoo Kim, Takayuki Katsuno,Takenori Ozaki, Waichi Sato, Enyu Imai, Seiichi Mats u o , S hoichi Maruyama
  • Organizer: 44rd Annual Meeting of The American Society of Nephrology
  • Place of Presentation: Philadelphia, PA
  • Year and Date: 2011-11-10
• [Presentation] 脂肪由来間葉系幹細胞を用いた壊死性半月体形成腎炎への新たな治療法の確立～骨髄由来間葉系細胞にはなく塩脂肪由来幹細胞がもつ Macrophage への unique chaqracter～ (2011)
  • Author(s): 古橋和拡 清水明日香 阿部智子 金恒秀 勝野敬之 尾崎武徳 佐藤和一 坪井直毅 丸山彰一 松尾清一
  • Organizer: 第三回 腎疾患と高血圧研究会
  • Place of Presentation: 大阪
  • Year and Date: 2011-06-27
• [Presentation] 脂肪由来間葉系幹細胞を用いた難治性腎疾患への新たな治療戦略 (2011)
  • Author(s): 古橋 和拡、清水 明日香、阿部 智子、金 恒秀、勝野 敬之、尾崎 武徳、佐藤 和一、坪井 直毅、今井 圓裕、丸山 彰一、松尾 清一
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-06-17
• [Presentation] 脂肪細胞由来幹細胞は腎臓をどう守るのか (2011)
  • Author(s): 丸山 彰一、古橋 和拡、勝野 敬之、尾崎 武徳、坪井 直毅、松尾 清一
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-06-15
• [Presentation] 脂肪由来間葉系幹細胞(ASC)を用いた難治性腎疾患・自己免疫疾患に対する新たな治療戦略 (2011)
  • Author(s): 古橋和拡 清水明日香 阿部智子 金恒秀 勝野敬之 尾崎武徳 ,坪井直毅 丸山彰一 松尾清一
  • Organizer: 再生医療学会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-01
• [Patent(Industrial Property Rights)] 糖尿病性腎症鑑別用マーカー及びその用途 (2012)
  • Inventor(s): 丸山彰一、湯澤由紀夫、松尾清一、佐藤和一、尾崎武徳、秋山真一、曽我朋義、平山明由
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Number: 2012-128588
  • Filing Date: 2012-09-14
• [Patent(Industrial Property Rights)] 脂肪組織由来多分化能幹細胞を含有する細胞製剤 (2006)
  • Inventor(s): 尾崎武徳、安田香、丸山彰一、山本徳則、後藤百万、松尾清一、北川泰雄
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Number: 2008-528826
  • Filing Date: 2006-08-23