Faculty Profiles - OGATA Aika

Performance of a biodegradable composite with hydroxyapatite as a scaffold in pulp tissue repair Reviewed Open Access

Motoki Okamoto, Sayako Matsumoto, Ayato Sugiyama, Kei Kanie, Masakatsu Watanabe, Hailing Huang, Manahil Ali, Yuki Ito, Jiro Miura, Yujiro Hirose, Koichiro Uto, Mitsuhiro Ebara, Ryuji Kato, Aika Yamawaki-Ogata, Yuji Narita, Shigetada Kawabata, Yusuke Takahashi, Mikako Hayashi

Polymers Vol. 12 ( 4 ) page： 937 - 937 2020.4

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Vital pulp therapy is an important endodontic treatment. Strategies using growth factors and biological molecules are effective in developing pulp capping materials based on wound healing by the dentin-pulp complex. Our group developed biodegradable viscoelastic polymer materials for tissue-engineered medical devices. The polymer contents help overcome the poor fracture toughness of hydroxyapatite (HAp)-facilitated osteogenic differentiation of pulp cells. However, the composition of this novel polymer remained unclear. This study evaluated a novel polymer composite, P(CL-co-DLLA) and HAp, as a direct pulp capping carrier for biological molecules. The biocompatibility of the novel polymer composite was evaluated by determining the cytotoxicity and proliferation of human dental stem cells in vitro. The novel polymer composite with BMP-2, which reportedly induced tertiary dentin, was tested as a direct pulp capping material in a rat model. Cytotoxicity and proliferation assays revealed that the biocompatibility of the novel polymer composite was similar to that of the control. The novel polymer composite with BMP-2-induced tertiary dentin, similar to hydraulic calcium-silicate cement, in the direct pulp capping model. The BMP-2 composite upregulated wound healing-related gene expression compared to the novel polymer composite alone. Therefore, we suggest that novel polymer composites could be effective carriers for pulp capping.

DOI： 10.3390/polym12040937

Hydrogen water alleviates obliterative airway disease in mice. Reviewed

Ozeki N, Yamawaki-Ogata A, Narita Y, Mii S, Ushida K, Ito M, Hirano SI, Kurokawa R, Ohno K, Usui A

General thoracic and cardiovascular surgery Vol. 68 ( 2 ) page： 158 - 163 2020.2

The oral administration of colchicine prevents the progression of aortic aneurysm Invited Reviewed

Okawa H., Yamawaki-Ogata A., Narita Y., Munakata H., Hashizume R., Usui A.

EUROPEAN HEART JOURNAL Vol. 40 page： 1882 - 1882 2019.10

Montelukast, a Cysteinyl Leukotriene Receptor 1 Antagonist, Induces M2 Macrophage Polarization and Inhibits Murine Aortic Aneurysm Formation. Invited Reviewed Open Access

Kawai Y, Narita Y, Yamawaki-Ogata A, Usui A, Komori K

BioMed research international Vol. 2019 page： 9104680 2019

The oral administration of clarithromycin prevents the progression and rupture of aortic aneurysm. Reviewed International journal Open Access

Uchida W, Narita Y, Yamawaki-Ogata A, Tokuda Y, Mutsuga M, Lee Fujimoto K, Abe T, Oshima H, Usui A

Journal of vascular surgery Vol. 68 ( 6S ) page： 82S - 92S.e2 2018.12

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The pathogenesis of aortic aneurysm (AA) is associated with chronic inflammation in the aortic wall with increased levels of matrix metalloproteinases (MMPs). Clarithromycin (CAM) has been reported to suppresses MMP activity. In this study, we investigated whether CAM could prevent the formation and rupture of AA. METHODS: Male apolipoprotein E-deficient mice (28-30 weeks of age) were infused with angiotensin II for 28 days. CAM (100 mg/kg/d) or saline (as a control) was administered orally to the mice every day (CAM group, n = 13; control group, n = 13). After the administration period, the aortic diameter, elastin content, macrophage infiltration, MMP levels, and levels of inflammatory cytokines, including nuclear factor κB (NF-κB), were measured. RESULTS: The aortic diameter was significantly suppressed in the CAM group (P < .001). No rupture death was observed in the CAM group in contrast to five deaths (38%) in the control group (P < .01). CAM significantly suppressed the degradation of aortic elastin (56.3% vs 16.5%; P < .001) and decreased the infiltration of inflammatory macrophages (0.05 vs 0.16; P < .01). Compared with the controls, the enzymatic activity of MMP-2 and MMP-9 was significantly reduced in the CAM group (MMP-2, 0.15 vs 0.56 [P < .01]; MMP-9, 0.12 vs 0.60 [P < .01]), and the levels of interleukin 1β (346.6 vs 1066.0; P < .05), interleukin 6 (128.4 vs 346.2; P < .05), and phosphorylation of NF-κB were also decreased (0.3 vs 2.0; P < .01). CONCLUSIONS: CAM suppressed the progression and rupture of AA through the suppression of inflammatory macrophage infiltration, a reduction in MMP-2 and MMP-9 activity, and the inhibition of elastin degradation associated with the suppression of NF-κB phosphorylation.

DOI： 10.1016/j.jvs.2017.12.047

Isolation and characterisation of peripheral blood-derived feline mesenchymal stem cells Reviewed

The Possibility of Clarithromycin for the Treatment of Type B Aortic Dissection. Invited Reviewed

Uchida Wataru, Yamawaki-Ogata Aika, Hideki Ito, Sachie Tarazawa, Tokuda Yoshiyuki, Mutsuga Masato, Fujimoto Kazuro L., Yuji Narita, Usui Akihiko

CIRCULATION Vol. 138 page： . 2018.11

Evaluation of the Bactericidal and Fungicidal Activities of Poly([2-(methacryloyloxy)ethyl]trimethyl Ammonium Chloride)(Poly (METAC))-Based Materials. Invited Reviewed Open Access

Shiga T, Mori H, Uemura K, Moriuchi R, Dohra H, Yamawaki-Ogata A, Narita Y, Saito A, Kotsuchibashi Y

Polymers Vol. 10 ( 9 ) 2018.8

Effects of exosomes derived from the induced pluripotent stem cells on skin wound healing Invited Reviewed Open Access

Hitoshi Kobayashi, Katsumi Ebisawa, Miki Kambe, Takatoshi Kasai, Hidetaka Suga, Kae Nakamura, Yuji Narita, Aika Ogata, Yuzuru Kamei

Nagoya Journal of Medical Science Vol. 80 ( 2 ) page： 141 - 153 2018.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Nagoya University

Recently, the effects of stem cell supernatants or exosomes, such as skin wounds, have attracted attention. However, the effects of the induced pluripotent stem (iPS) cell-derived exosomes (iPS-Exos) have not been investigated in detail. Here, we investigated the effects of iPS-Exos on skin wound healing using an animal model. We isolated iPS-Exos from the iPS cell culture media. Control exosomes were isolated from unused iPS cell culture media (M-Exos). We first observed the morphologic characteristics of the isolated exosomes and examined the expression of surface antigens. The effects of these exosomes on the migratory response and proliferation of fibroblasts were analyzed as well. Additionally, using a diabetic ulcer model, the effects of iPS-Exos and M-Exos on skin wound healing were investigated. Transmission electron microscope analysis demonstrated that the size of iPS-Exos (120 ± 25 nm) was significantly larger than that of M-Exos (≤ 100 nm). Flow cytometry analyses showed that iPS-Exos were positive for CD9, CD63, and CD81, whereas they were negative for HLA-ABC and -DR expression. The migratory ability of fibroblasts cocultured with iPS-Exos was shown to be higher than that of the cells cocultured with M-Exos, as demonstrated using scratch assay. Skin wound healing model results showed that the administration of iPS-Exos results in a faster wound closure compared with that observed in the M-Exo group. In conclusion, the results obtained here indicate that iPS-Exos may promote the migration of fibroblasts in vitro and in vivo, suggesting the possibility of using iPS-Exos for the treatment of diabetic ulcer.

DOI： 10.18999/nagjms.80.2.141

Clarithromycinの大動脈瘤発生抑制効果の作用機序の解明 Invited Reviewed

内田亘, 成田裕司, 緒方藍歌, 伊藤英樹, 山名孝治, 寺澤幸枝, 徳田順之, 六鹿雅登, 藤本和朗, 阿部知伸, 大島英揮, 碓氷章彦

日本心臓血管外科学会学術総会抄録集 Vol. 47回 page： 850 - 850 2017.2

Keiichi Sato, Aika Yamawaki-Ogata, Isamu Kanemoto, Akihiko Usui, Yuji Narita

VETERINARY JOURNAL Vol. 216 page： 183 - 8 2016.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

The aim of this study was to isolate mesenchymal stem cells (MSCs) from feline peripheral blood (fPB-MSCs) and to characterise the cells' in vitro properties. The mononuclear cell fractions were isolated from venous blood of cats by density gradient centrifugation and cultured on plastic dishes under various culture conditions to isolate MSCs. When these cells were cultured with 5% autologous plasma (AP) and 10% foetal bovine serum (FBS), adherent spindle shaped fibroblast-like cells (fPB-MSCs) were obtained from 15/22 (68%) cats. These cells were isolated only from medium containing both AP and FBS. The morphology of these MSCs was similar to those isolated from other species and from other feline tissues. fPB-MSCs expanded steadily up to 5-6 passages, but had increased population doubling time during passaging and almost all cells stopped proliferation at passages 7-9. These cells expressed CD44 and CD90, and were mostly negative for major histocompatibility class II and CD4. The cells could be induced to differentiate into adipogenic, osteogenic and chondrogenic cell lineages. These findings indicate that fPB-MSCs can be generated but appear to require specific culture conditions. (C) 2016 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tvjl.2016.08.009

大動脈瘤に対する幹細胞療法効果のメカニズムに関して Invited Reviewed

成田裕司, 緒方藍歌, 小坂井基史, 藤本和朗, 六鹿雅登, 阿部知伸, 大島英揮, 碓氷章彦

日本心臓血管外科学会学術総会抄録集 Vol. 46回 page： OP10 - 2 2016.2

Exosomes Obtained from Mesenchymal Stem Cells as a Novel Therapeutic Tool for Aortic Aneurysm Invited Reviewed

A. Yamawaki-ogata, M. Kosakai, A. Usui, Y. Narita

TISSUE ENGINEERING PART A Vol. 21 page： S211 - S212 2015.9

Skin-Derived Precursor Cells Promote Wound Healing in Diabetic Mice Reviewed

Hideyoshi Sato, Katsumi Ebisawa, Keisuke Takanari, Shunjiro Yagi, Kazuhiro Toriyama, Aika Yamawaki-Ogata, Yuzuru Kamei

ANNALS OF PLASTIC SURGERY Vol. 74 ( 1 ) page： 114 - 20 2015.1

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Background: Impaired wound healing as one of the complications arising from diabetes mellitus is a serious clinical issue. Recently, various cell therapies have been reported for promotion of wound healing. Skin-derived precursor cells (SKPs) are multipotent adult stem cells with the tendency to differentiate into neurons. We investigated the potency of promoting diabetic wound healing by the application of SKPs.
Methods: Skin-derived precursor cells isolated from diabetic murine skin were cultured in sphere formation medium. At passage 2, they were suspended in phosphate-buffered saline (PBS), and applied topically to full-thickness excisional cutaneous wounds in diabetic mice. Application of PBS served as controls (n = 21 for each group; n = 42 total).
Time to closure and percentage closure were calculated by morphometry. Wounds were harvested at 10 and 28 days and then processed, sectioned, and stained (CD31, alpha-smooth muscle actin, and neurofilament heavy chain) to quantify vascularity and neurofilaments.
Results: Wounds treated with SKPs demonstrated a significantly decreased time to closure (18.63 days) compared with PBS-control wounds (21.72 days, P > 0.01), and a significant improvement in percentage closure at 7, 10, 14, and 18 days compared with PBS-control wounds (P > 0.01). Histological analysis showed that the Capillary Score (the number of vessels/mm(2)) was significantly higher in SKP-treated wounds at day 10 but not at day 28. Nerve Density (the number of neurofilaments/mm(2)) had increased significantly in SKP-treated wounds at day 28 compared with control group. Some applied SKPs were stained by neurofilament heavy chain, which demonstrates that SKPs directly differentiated into neurons.
Conclusions: Skin-derived precursor cells promoted diabetic wound healings through vasculogenesis at the early stage of wound healing. Skin-derived precursor cells are a possible therapeutic tool for diabetic impaired wound healing.

DOI： 10.1097/SAP.0000000000000342

大動脈瘤に対する幹細胞療法投与法による大動脈瘤進展抑制効果の違い Invited Reviewed

成田裕司, 緒方藍歌, 符顕明, 荒木善盛, 阿部知伸, 大島英揮, 碓氷章彦

日本心臓血管外科学会雑誌 Vol. 43 ( Suppl. ) page： 263 - 263 2014.1

Intravenous administration of mesenchymal stem cells prevents angiotensin II-induced aortic aneurysm formation in apolipoprotein E-deficient mouse Reviewed Open Access

Xian-ming Fu, Aika Yamawaki-Ogata, Hideki Oshima, Yuichi Ueda, Akihiko Usui, Yuji Narita

JOURNAL OF TRANSLATIONAL MEDICINE Vol. 11 ( 1 ) page： 175 2013.7

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: Mesenchymal stem cells (MSCs) are known to be capable of suppressing inflammatory responses. We previously reported that intra-abdominal implantation of bone marrow-derived MSCs (BM-MSCs) sheet by laparotomy attenuated angiotensin II (AngII)-induced aortic aneurysm (AA) growth in apolipoprotein E-deficient (apoE(-/-)) mice through anti-inflammation effects. However, cell delivery by laparotomy is invasive; we here demonstrated the effects of multiple intravenous administrations of BM-MSCs on AngII-induced AA formation.
Methods: BM-MSCs were isolated from femurs and tibiae of male apoE(-/-) mice. Experimental AA was induced by AngII infusion for 28 days in apoE(-/-) mice. Mice received weekly intravenous administration of BM-MSCs (n=12) or saline (n=10). After 4 weeks, AA formation incidence, aortic diameter, macrophage accumulation, matrix metalloproteinase (MMP)' activity, elastin content, and cytokines were evaluated.
Results: AngII induced AA formation in 100% of the mice in the saline group and 50% in the BM-MSCs treatment group (P < 0.05). A significant decrease of aortic diameter was observed in the BM-MSCs treatment group at ascending and infrarenal levels, which was associated with decreased macrophage infiltration and suppressed activities of MMP-2 and MMP-9 in aortic tissues, as well as a preservation of elastin content of aortic tissues. In addition, interleukin (IL)-1 beta, IL-6, and monocyte chemotactic protein-1 significantly decreased while insulin-like growth factor-1 and tissue inhibitor of metalloproteinases-2 increased in the aortic tissues of BM-MSCs treatment group.
Conclusions: Multiple intravenous administrations of BM-MSCs attenuated the development of AngII-induced AA in apoE(-/-) mice and may become a promising alternative therapeutic strategy for AA progression.

DOI： 10.1186/1479-5876-11-175

Prevention of arterial graft spasm in rats using a vasodilator-eluting biodegradable nano-scaled fibre Reviewed Open Access

Kei Yagami, Aika Yamawaki-Ogata, Makoto Satake, Hiroaki Kaneko, Hideki Oshima, Akihiko Usui, Yuichi Ueda, Yuji Narita

Interactive Cardiovascular and Thoracic Surgery Vol. 17 ( 1 ) page： 16 - 22 2013.7

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVESArterial graft spasm occasionally causes circulatory collapse immediately following coronary artery bypass graft. The aim of this study is to evaluate the efficacy of our developed materials, which were composed of milrinone (phosphodiesterase III inhibitor) or diltiazem (calcium-channel blocker), with nano-scaled fibre made of biodegradable polymer to prevent arterial spasm.METHODSMilrinone- or diltiazem-releasing biodegradable nano-scaled fibres were fabricated by an electrospinning procedure. In vivo milrinone- or diltiazem-releasing tests were performed to confirm the sustained release of the drugs. An in vivo arterial spasm model was established by subcutaneous injection of noradrenalin around the rat femoral artery. Rats were randomly divided into four groups as follows: those that received 5 mg of milrinone-releasing biodegradable nano-scaled fibre (group M, n = 14)
5 mg of diltiazem-releasing biodegradable nano-scaled fibre (group D, n = 12)
or those that received fibre without drugs (as a control
group C, n = 14) implanted into the rat femoral artery. In the fourth group, sham operation was performed (group S, n = 10). One day after the implantation, noradrenalin was injected in all groups. The femoral arterial blood flow was measured continuously before and after noradrenalin injection. The maximum blood flow before noradrenalin injection and minimum blood flow after noradrenalin injection were measured.RESULTSIn vivo drug-releasing test revealed that milrinone-releasing biodegradable nano-scaled fibre released 78% of milrinone and diltiazem-releasing biodegradable nano-scaled fibre released 50% diltiazem on the first day. The ratios of rat femoral artery blood flow after/before noradrenalin injection in groups M (0.74 ± 0.16) and D (0.72 ± 0.05) were significantly higher than those of groups C (0.54 ± 0.09) and S (0.55 ± 0.16) (P &lt
0.05).CONCLUSIONNoradrenalin-induced rat femoral artery spasm was inhibited by the implantation of milrinone-releasing biodegradable nano-scaled fibre or diltiazem-releasing biodegradable nano-scaled fibre. These results suggested that our materials might be effective for the prevention of arterial graft spasm after coronary artery bypass graft. © 2013 The Author. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

DOI： 10.1093/icvts/ivt092

Long-term results of tissue-engineered small-caliber vascular grafts in a rat carotid arterial replacement model Reviewed

KUWABARA Fumiaki, NARITA Yuji, YAMAWAKI OGATA Aika, SATAKE Makoto, KANEKO Hiroaki, OSHIMA Hideki, USUI Akihiko, UEDA Yuichi

Vol. 15 ( 4 ) page： 399 - 405 2012.12

Long-term results of tissue-engineered small-caliber vascular grafts in a rat carotid arterial replacement model Reviewed

Fumiaki Kuwabara, Yuji Narita, Aika Yamawaki-Ogata, Makoto Satake, Hiroaki Kaneko, Hideki Oshima, Akihiko Usui, Yuichi Ueda

JOURNAL OF ARTIFICIAL ORGANS Vol. 15 ( 4 ) page： 399 - 405 2012.12

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

The concept of tissue engineered small-caliber vascular grafts (TE-SCVGs) is theoretically ideal. In this study, we evaluated the long-term (more than 1 year) course of TE-SCVGs using a rat carotid arterial replacement model. We fabricated a TE-SCVG scaffold (0.7 mm in diameter) with electrospun nano-scale fibers. Poly-epsilon-caprolactone was used as a biodegradable polymer. These artificial vessels were then used in carotid arterial replacement performed on Sprague-Dawley rats. The implanted grafts were removed at an early phase (1, 2, 6 weeks), middle phase (12, 24 weeks), and late phase (48, 72 weeks) after implantation. Twenty-nine patent grafts from among the 40 implanted grafts (patency 72.5 %) could be evaluated. No aneurysm formation was observed during the follow-up period. Endothelial cells positive for immunostaining with von Willebrand factor were found to be already attached to the inner surface of the TE-SCVGs in the early phase. The percentage of smooth muscle cell specific marker (a-smooth muscle actin and calponin with fluorescent immunostaining) positive cells, which seemed to be mesenchymal cells in the graft wall, increased with time, while, in contrast, the scaffold material decreased. Even after 72 weeks, however, although the scaffold material had degraded, it had not disappeared completely. These results show that the novel TE-SCVGs we developed were still functioning in the rat carotid arterial circulation after more than 1 year. However, further investigations will be required with regard to regeneration of the SMC layer and the complete degradation of graft materials.

DOI： 10.1007/s10047-012-0652-6