Papers - HATTORI Hidemi
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Kishimoto S., Kishimoto S., Kishimoto S., Ishihara M., Mori Y., Mori Y., Takikawa M., Hattori H., Nakamura S., Sato T.
Journal of Tissue Engineering and Regenerative Medicine 7 ( 12 ) 955 - 964 2013.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Tissue Engineering and Regenerative Medicine
Fragmin/protamine nanoparticles (F/P NPs) can be stably coated onto plastic surfaces and used as a substratum for the absorption and controlled release of growth factors (GFs) secreted from human platelet-rich plasma (PRP). In this study, we investigated the capability of F/P NP-coated plates to act as a substratum for the proliferation of human adipose-derived stromal cells (ASCs) and bone marrow-derived mesenchymal stem cells (BMSCs) with GFs in PRP. Both cell types adhered well to the F/P NP-coated plates and grew optimally, with a doubling time of 30 and 32 h in low-concentration PRP (0.5%) medium supplemented with 5 ng/ml fibroblast growth factor-2 (FGF-2) on the F/P NP-coated plates. These cells maintained their multilineage potential for differentiation into adipocytes or osteoblasts. Furthermore, ASCs and BMSCs grew well in medium without PRP and FGF-2 on F/P NP-coated plates pretreated with PRP and FGF-2 in a concentration-dependent manner. Thus, F/P NP-coated plates are a useful substratum for the adherence and proliferation of ASCs and BMSCs in low-concentration PRP medium supplemented with FGF-2. No xenogeneic serum is required. © 2012 John Wiley & Sons, Ltd.
DOI： 10.1002/term.1488
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Nguyen V., Ishihara M., Mori Y., Nakamura S., Kishimoto S., Fujita M., Hattori H., Kanatani Y., Ono T., Miyahira Y., Matsui T.
Bio-Medical Materials and Engineering 23 ( 6 ) 473 - 483 2013.11
Language：English Publishing type：Research paper (scientific journal) Publisher：Bio-Medical Materials and Engineering
We previously reported a simple method for the preparation of size-controlled spherical silver nanoparticles (Ag NPs) generated by autoclaving a mixture of silver-containing glass powder and glucose. The particle size is regulated by the glucose concentration, with concentrations of 0.25, 1.0 and 4.0 wt% glucose providing small (3.48±1.83 nm in diameter), medium (6.53±1.78 nm) and large (12.9±2.5 nm) particles, respectively. In this study, Ag NP/chitosan composites were synthesized by mixing each of these three Ag NP suspensions with a 75% deacetylated (DAc) chitosan suspension (pH 5.0) at room temperature. The Ag NPs were homogeneously dispersed and stably embedded in the chitosan matrices. The Ag NP/chitosan composites were obtained as yellow or brown flocs. It was estimated that approximately 60, 120 and 360 μg of the small, medium and large Ag NPs, respectively, were maximally embedded in 1 mg of chitosan. The bactericidal and anti-fungal activities of the Ag NP/chitosan composites increased as the amount of Ag NPs in the chitosan matrix increased. Furthermore, smaller Ag NPs (per weight) in the chitosan composites provided higher bactericidal and anti-fungal activities. © 2013 - IOS Press and the authors.
DOI： 10.3233/BME-130772
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Nguyen V., Ishihara M., Nakamura S., Hattori H., Ono T., Miyahira Y., Matsui T.
Journal of Nanomaterials 2013 2013.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Nanomaterials
Silver nanoparticles (Ag NPs) were 5.17±1.9 nm in diameter, and four <5% deacetylated chitins (A, B, C, and D) differing in size of powder and surface structure properties were used in the study. Chitin/Ag NP composites were synthesized by mixing Ag NP suspensions with each chitin powder at room temperature for 30 min. The Ag NPs were homogenously dispersed and stably adsorbed onto the chitins A and B powders. The resulting chitin/Ag NP composites were brown; darker composites were obtained when larger amounts of Ag NPs were reacted with chitin. Approximately, 26 and 22 g of Ag NPs maximally adsorbed to 1 mg of chitins A and B, respectively, whereas only 2.5 and 1.5 g of Ag NPs maximally adsorbed to chitins C and D, respectively. As the bactericidal and antifungal activities of the chitin/Ag NP composites increased with increasing amounts of Ag NPs adsorbed to the chitin, the antimicrobial activity of chitins A and B/Ag NP composites was much higher than that of chitins C and D/Ag NP composites. These results suggest that the particle size and surface structure of the chitin powder critically influence both the adsorption and antimicrobial activity of Ag NPs. © 2013 Vinh Quang Nguyen et al.
DOI： 10.1155/2013/467534
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Takase B., Hattori H., Tanaka Y., Uehata A., Nagata M., Ishihara M., Fujita M.
Journal of Cardiovascular Ultrasound 21 ( 3 ) 130 - 136 2013.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Cardiovascular Ultrasound
Background: Repeated application of whole-body periodic acceleration (WBPA) upregulates endothelial nitric oxide synthase and improves brachial artery endothelial function (BAEF) as assessed by measurement of flow-mediated vasodilatation (FMD). However, the acute effect of a single application of WBPA on BAEF has not been fully characterized. In addition, although a novel semi-automatic vessel chasing system (UNEXEF18G) has now been developed in Japan, the direct comparison of UNEXEF18G with a conventional method for FMD measures has not been conducted even if UNEXEF18G has already been utilized in a relatively large scale study. Methods: We have developed a novel semi-automatic vessel chasing system (UNEXEF18G) that can measure FMD on-line, identify time to peak vasodilatation (TPV), and determine the area under the vasodilatation curve (AUC). Thus, 45 min of WBPA was applied in 20 healthy volunteers (age, 34 ± 13 years), and BAEF was measured by UNEXEF18G before and after WBPA. Also, UNEXEF18G measured FMD was compared with those of a conventional FMD measurement method at rest in order to validate a novel UNEXEF18G measured FMD. Results: Single WBPA resulted in a significant increase in FMD (from 6.4 ± 3.4 to 10.7 ± 4.3%, p < 0.01), a significant decrease in TPV and a significant increase in AUC. In the validation study for UNEXEF18G, Bland and Altman analysis showed that UNEXEF18G measured FMD was almost identical to those of the conventional method at rest. Conclusion: These data suggest the usefulness of a new UNEXEF18G and that single application of WBPA results in acute improvement in BAEF in humans. © 2013 Korean Society of Echocardiography.
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Tsuda Y., Hattori H., Tanaka Y., Ishihara M., Kishimoto S., Kishimoto S., Amako M., Arino H., Nemoto K.
Journal of Tissue Engineering and Regenerative Medicine 7 ( 9 ) 720 - 728 2013.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Tissue Engineering and Regenerative Medicine
In the field of orthopaedic surgery, an orthopaedic surgeon sometimes requires to suppress excessive bone formation, such as ectopic bone formation, ossifying myositis and radio-ulnar synostosis, etc. Ultraviolet (UV) light irradiation of a photocrosslinkable chitosan (Az-CH-LA) generates an insoluble hydrogel within 30s. The purpose of this study was to evaluate the ability of the photocrosslinked chitosan hydrogel (PCH) to inhibit bone formation in an experimental model of bone defect. Rat calvarium and fibula were surgically injured and PCH was implanted into the resultant bone defects. The PCH implants significantly prevented bone formation in the bone defects during the 4 and 8week observation periods. In the PCH-treated defects, fibrous tissues infiltrated by inflammatory cells were formed by day 7, completely filling the bone defects. In addition to these findings, expression of osteocalcin and runt-related gene 2 (RUNX2) mRNA, both markers of bone formation, was lower in the PCH-treated defects than in the controls. In contrast, collagen type 1α2 and α-smooth muscle actin (α-SMA) mRNA levels were significantly higher in the PCH-treated defects after 1week. PCH stimulated the formation of fibrous tissue in bone defects while inhibiting bone formation. Thus, PCH might be a promising new therapeutic biomaterial for the prevention of bone formation in orthopaedic surgery. © 2012 John Wiley & Sons, Ltd.
DOI： 10.1002/term.1462
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出血性ショック心臓における致死性不整脈の機序に関する実験的検討―活動電位不均一性とConnexin43変化について Invited Reviewed
高瀬凡平, 東村悠子, 木村一生, 田中良弘, 服部秀美, 石原雅之.
Therapeutic Research 34 ( 8 ) 1060 - 6 2013.8
Language：Japanese Publishing type：Research paper (conference, symposium, etc.)
出血性ショックにより平均全身血圧が40mmHg以下に低下遷延すると，不可逆性心筋障害が発生し，いわゆる“出血性ショック心臓”といわれる致死性の病態を呈するとされている。しかし，致死性不整脈の発生機序に関する
検討は少ない。そこでわれわれは，実験的に検討した。
方法：SD rat （n＝32）に30％出血性ショック状態を作製し，非蘇生群，洗浄赤血球蘇生群，生理食塩水蘇生群，5％アルブミン蘇生群の4群間で心筋を摘出Tyrode液で灌流後Na channel感受性色素を用いたoptical mapping system
（OMP）で興奮伝播・活動電位持続時間不均一性（action potential duration dispersion ：APD dispersion），致死性催不整脈性を検討した。また，心筋組織のconnexin43 （Cx43）発現を免疫
組織染色にて検討した。
結果：蘇生群では，3群とも全例蘇生に成功した。しかし，生理食塩水群，5％アルブミン群では OMP で著明な左心室伝導遅延と burst pacingによる心室細動が全例で誘発されたのに対し，洗浄赤血球蘇生群では，伝導遅延・心室細動誘発ともに認められなかった。生理食塩水群，5％アルブミン群では著明にAPD dispersion値が増大したが，洗浄赤血球群では正常に保たれていた。connexin43発現は生理食塩水群，5％アルブミン群では異常が認められたものの，洗浄赤血球群では正常に保たれていた。
結語：出血性ショック心臓では，左心室伝導遅延とAPD dispersion増大およびconnexin43発現異常を惹起し，電気的不安定性から致死性不整脈が誘発されることが示唆された。洗浄赤血球治療はこれら指標の保持と予防効果を有した。 -
Sumi Y., Ishihara M., Kishimoto S., Kishimoto S., Takikawa M., Doumoto T., Azuma R., Nakamura S., Hattori H., Fujita M., Kiyosawa T.
Journal of Biomedical Materials Research - Part B Applied Biomaterials 101 B ( 5 ) 784 - 791 2013.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biomedical Materials Research - Part B Applied Biomaterials
Fragmin/protamine microparticles (F/P MPs) have been used as a cell carrier for adipose-derived stromal cells (IR-ASCs) in inbred male Fisher 344 rats, and for preservation and controlled-release of fibroblast growth factor (FGF)-2 and various cytokines in inbred rat plasma (IRP)-DMEM (Dulbecco's modified Eagle's medium) gel. In this study, we investigated the capability of an IRP-DMEM gel containing F/P MPs and/or FGF-2, as a three-dimensional (3D)-culture, to expand IR-ASCs. We found that IR-ASCs grow faster under 3D-culture conditions in low IRP (3%)-DMEM gel containing F/P MPs and FGF-2 without any animal serum than those under 2D-culture in low inbred rat serum (3%)-DMEM with F/P MPs and FGF-2. About 0.3 mL of IR-ASCs (about 4,000,000 cells mL-1) grown in IRP (6%)-DMEM gel containing F/P MPs and FGF-2 disappeared 8 days after subcutaneous injection in rats, suggesting that they are rapidly biodegradable. The number of large (diameter ≥200 μm or containing ≥100 erythrocytes), medium (diameter = 20-200 μm or containing 10-100 erythrocytes) and small (diameter ≤20 μm or containing 1-10 erythrocytes) capillaries after injection with IR-ASCs in an IRP-DMEM gel containing both F/P MPs and FGF-2, as well as the thickness of tissue granulation per microphotograph at the injected site, was significantly higher than those after injection with IR-ASCs in an IRP-DMEM gel containing either FGF-2 or F/P MPs. Thus, IRP-DMEM gel containing F/P MPs and FGF-2 are useful and safe IR-ASC carriers that facilitate cell proliferation, vascularization, and tissue granulation locally at injection sites. © 2013 Wiley Periodicals, Inc.
DOI： 10.1002/jbm.b.32882
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血管内皮機能指標の疾患別測定値変動に関する検討 : 心臓リハビリテーション効果判定に関して. Invited Reviewed
高瀬凡平, 永田雅良, 服部秀美, 石原雅之.
心臓リハビリテーション 18 ( 2 ) 231 - 5 2013.6
Language：Japanese Publishing type：Research paper (scientific journal)
[目的] 上腕動脈血管内皮機能検査(Flow-mediated vasodilatation: FMD)は動脈硬化指標として広く用いられている. しかし, FMD測定値に及ぼす因子は多岐にわたるので, 疾患別測定値変動幅を検討する. [方法] 冠動脈危険因子を有する健常者(HV; n=10), 高血圧例(HT; n=34)および冠動脈疾患例(CAD: n=35)に約3年間で少なくとも4回以上のFMD測定を施行し, その変動値につき検討を加えた. この間, 個々のFMD測定は通常のガイドラインに準拠し, FMD測定専用機(UNEXEF)で測定したものの, 期間中の治療内容は主治医の判断により変更可とした. 変動程度は個々の症例の測定値の標準偏差(SD)を求め, 3群間でそのSDの平均±標準偏差を算出して評価した. [結果] 安静時上腕動脈の血管径変動値には3群間で有意差は認められなかった. しかし, FMDはHV群に有意に変動が大きいことが認められた(HV vs HT, CAD; 2.4±1.1 vs 1.4±1.0, 1.0±0.9%, p<0.05). [結論] 上腕動脈血管内皮機能は動脈硬化疾患の進展・予後を規定する検査法として今後ますます重視される項目である. したがって, 上腕動脈血管内皮機能検査法で得られるFMD値の改善基準を, 代表的検査対象である, 健常者例, 高血圧症例, 冠動脈疾患症例で示した. 今後の心臓リハビリテーションなどのinterventionがFMD値に及ぼす影響を検討するうえで有用と考え報告した.
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Development of a Novel Emergency Hemostatic Kit for Severe Hemorrhage Reviewed
Hattori H., Amano Y., Nogami Y., Kawakami M., Yura H., Ishihara M.
Artificial Organs 37 ( 5 ) 475 - 481 2013.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Artificial Organs
Photocrosslinkable chitosan (Az-CH-LA) contains lactose moieties and photoreactive azide groups, and its viscous solution forms an insoluble hydrogel on exposure to UV irradiation. We previously developed an emergency hemostatic kit using the Az-CH-LA solution, calcium alginate, and a UV irradiation apparatus. However, a suitable UV irradiation apparatus is required to effectively convert the Az-CH-LA solution into a hydrogel, and power supply to use the UV irradiation apparatus may not always be available in a disaster area or battlefield. To address this problem, we produced a portable, battery-powered UV irradiation apparatus constituting a novel hemostatic kit for severe hemorrhage. When the hemostatic kit using the UV irradiation apparatus was examined using a rat model of severe hemorrhage, the survival rate increased up to 73%. Hematological values as markers of hemorrhage did not change significantly over the first 3 days. In this study, we describe the characteristics of a portable UV irradiation apparatus and its use in an emergency hemostatic kit prepared using Az-CH-LA and calcium alginate for severe hemorrhage. © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
DOI： 10.1111/aor.12004
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Nguyen V., Ishihara M., Mori Y., Nakamura S., Kishimoto S., Hattori H., Fujita M., Kanatani Y., Ono T., Miyahira Y., Matsui T.
Journal of Nanomaterials 2013 2013.4
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Nanomaterials
A simple method for the preparation of size-controlled spherical silver nanoparticles (Ag NPs) was reported for their generation by autoclaving a mixture of silver-containing glass powder and glucose. The particle size is regulated by the glucose concentration, with concentrations of 0.25, 1.0, and 4.0 wt% glucose providing small (3.48 ± 1.83 nm in diameter), medium (6.53 ± 1.78 nm), and large (12.9 ± 2.5 nm) particles, respectively. In this study, Ag NP/chitin composites were synthesized by mixing each of these three Ag NP suspensions with a <5% deacetylated (DAc) chitin powder (pH 7.0) at room temperature. The Ag NPs were homogenously dispersed and stably adsorbed onto the chitin. The Ag NP/chitin composites were obtained as yellow or brown powders. Approximately 5, 15, and 20 g of the small, medium, and large Ag NPs, respectively, were estimated to maximally adsorb onto 1 mg of chitin. The bactericidal and antifungal activities of the Ag NP/chitin composites increased as the amount of Ag NPs in the chitin increased. Furthermore, smaller Ag NPs (per weight) in the chitin composites provided higher bactericidal and anti-fungal activities. © 2013 Vinh Quang Nguyen et al.
DOI： 10.1155/2013/693486
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Fujita M., Horio T., Kishimoto S., Kishimoto S., Nakamura S., Takikawa M., Nakayama T., Yamamoto Y., Shimizu M., Hattori H., Tachibana S., Ishihara M.
Journal of Biomedical Materials Research - Part B Applied Biomaterials 101 B ( 1 ) 36 - 42 2013.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biomedical Materials Research - Part B Applied Biomaterials
The purpose of the study was to evaluate the effects of isogenous platelet-rich plasma (PRP)-containing fragmin/protamine microparticles (F/P MPs) as a delivery system for proteins in PRP on growth of endothelial and smooth muscle cells (SMCs) in vitro and as an alternative treatment for peripheral arterial disease (PAD) and critical limb ischemia. Frozen and thawed PRP contains high concentrations of growth factors that are adsorbed by F/P MPs. Human aorta endothelial cells (AECs) and SMCs were grown in a medium with PRP. Addition of F/P MPs significantly enhanced the proliferative effects of PRP on AECs and SMCs at 37°C for >10 days. Intramuscular administration of phosphate-buffered saline (PBS; 2 mL, control), F/P MPs (12 mg in 2 mL PBS), PRP (2 mL), or PRP (2 mL) containing F/P MPs (12 mg) was then performed in a rabbit model of hindlimb ischemia prepared by resection of the left femoral artery. Blood flow and pressure were measured on days 0, 14, and 28, and angiography to assess arteriogenesis was performed on day 28. PRP-containing F/P MPs strongly induced functional collateral vessels in the rabbit model of hindlimb ischemia, indicating possible use of these microparticles in therapy for PAD. © 2012 Wiley Periodicals, Inc.
DOI： 10.1002/jbm.b.32808
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Pitavastatin subacutely improves endothelial function and reduces inflammatory cytokines and chemokines in patients with hypercholesterolaemia. Reviewed
Takase B, Hattori H, Tanaka Y, Nagata M, Ishihara M
Heart Asia 5 ( 1 ) 204 - 9 2013
Language：English Publishing type：Research paper (scientific journal)
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画像診断と体表面微小電位 心臓MRI法、体表心臓微小電位および非侵襲的心電図予後指標に関する検討 Invited Reviewed
高瀬凡平, 永田雅良, 浜部晃, 上畑 昭美, 服部秀美, 田中良弘, 石原雅之, 栗田明.
心臓 45 ( Suppl. 1 ) 23 - 7 2013
Language：Japanese Publishing type：Research paper (conference, symposium, etc.)
心筋壊死診断に心臓MRI法の遅延造影（delayed enhancement；DE）が有用であり，DEと心筋梗塞（MI）後の予後の関連が報告されているものの，致死性不整脈発生の非侵襲的心電図予測指標との比較検討は少ない．そこで，DEと体表微小心臓電位（LP）やQT dispersion（QTD）と関係および予後予測につき検討した．
陳旧性心筋梗塞症84例（69± 9 歳）に心臓MRI法とLP，QTDを施行した．心臓MRI法は1.5T GE社製Sigma CV/iにてgadlinium投与造影下に左心室短軸 6 断面を撮像した．心筋の壊死形態をmassive（ 1 点）からpatchy（ 3 点）までscore化し（patchy sore；PS），LP陽性およびQTDの結果と比較した．症例を平均35±17カ月追跡調査し心事故との関連を調べた．
LP陽性例22例とLP陰性例62例が認められ，壊死の形態を示すPSはLP陽性例で陰性例に比べ高値を示した（2.3±0.5 vs 1.4±0.6，p＜0.05）．壊死範囲を反映するDE断面数とQTDは相関した．追跡期間中 9 例の心事故が認められDE断面数とQTDが心事故予測に有用であった．
結語：心臓MRI法で求めたDEの形態はLPと相関したものの，予後予測には壊死範囲を示すDE指標やQTDがより有用である可能性が示唆された． -
Nogami Y., Takase B., Kinoshita M., Shono S., Kaneda S., Tanaka Y., Kishimoto S., Hattori H., Ishihara M.
Shock 38 ( 2 ) 159 - 164 2012.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Shock
The use of liposome-encapsulated hemoglobin (LHb), which is a cellular Hb, has been demonstrated to be beneficial in the treatment of hypohemoglobinemic shock. As a molecule of appropriate size (220 nm) that can carry oxygen, LHb may ameliorate cardiac dysfunction during lethal hemodilation. The purpose of this study was to determine the efficacy of LHb transfusion in relieving cardiovascular dysfunction in a rat model of lethal progressive hemodilution. Over the course of 150 min, rats were subjected to blood withdrawal (0.2 mL/min) and simultaneously transfused with LHb, washed rat red blood cells, or 5% albumin. Temporal changes in cardiac function, heart-type fatty acid-binding protein levels, plasma levels of catecholamines, heart rate variability, and hypoxia-inducible factor 1α expression were measured during lethal progressive hemodilution. More than 80% of the rats transfused with either LHb or washed rat red blood cells survived for 8 days. Liposome-encapsulated hemoglobin transfusion suppressed hypoxia-inducible factor 1α expression in the heart, maintained low levels of heart-type fatty acid-binding protein, and attenuated sympathetic nerve activity as reflected by changes in heart rate variability and plasma levels of epinephrine and norepinephrine. The results indicate that LHb attenuates cardiac dysfunction and sympathetic overactivity during lethal hemorrhage. © 2012 by the Shock Society.
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Importance of Platypnea Orthodeoxia in the Differential Diagnosis of Dyspnea Invited
Takase B, Tanaka Y, Hattori H, Ishihara M.
Internal Medicine 51 ( 13 ) 1651 - 2 2012.7
Language：English Publishing type：Research paper (other academic)
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Kumano I., Ishihara M., Nakamura S., Kishimoto S., Fujita M., Hattori H., Horio T., Tanaka Y., Hase K., Maehara T.
Gastrointestinal Endoscopy 75 ( 4 ) 841 - 848 2012.4
Language：English Publishing type：Research paper (scientific journal) Publisher：Gastrointestinal Endoscopy
Background: Hypertonic saline solution (HS) as a submucosal fluid cushion (SFC) for endoscopic submucosal dissection (ESD) has several disadvantages, including a short effect duration and increased risk of bleeding and perforation. Photocrosslinkable chitosan hydrogel in DMEM/F12 medium (PCH) can be converted into an insoluble hydrogel by UV irradiation for 30 seconds. Objective: To evaluate the feasibility, usefulness, and safety of PCH as an SFC for ESD of esophagi, compared with HS and sodium hyaluronate (SH). Design: Survival animal study. Settings: Research laboratory study of 24 pig models in vivo. Interventions: Twenty-four pigs were used in the 2 steps: First, ESD of the esophagus was performed with PCH, SH, or HS (each n = 6) as an SFC, and the effects of these agents on wound healing were examined endoscopically and histologically. Second, in vivo degradation of PCH (n = 3) and HS (n = 3) was examined in independent pig esophagi. Main Outcome Measurements: Outcome measurements included feasibility and safety of PCH-assisted ESD of esophagus, gross and histologic evidence of the treated esophagus, biodegradation of injected PCH, and clinical tolerance by the animals. Result: PCH injection led to a longer-lasting elevation with clearer margins compared with SH and HS, thus enabling precise ESD along the margins of the elevated mucosa without complications such as bleeding and perforation. The aspects of wound repair after PCH-assisted ESD were similar to those of SH- and HS-assisted ESDs. Biodegradation of PCH was confirmed to be almost completed within 8 weeks on the basis of endoscopic and histologic observations. Limitations: In vivo animal model study. Conclusion: PCH permits more reliable ESD of the esophagus without complications than do SH and HS. Furthermore, the applied PCH appeared to be completely biodegraded within 8 weeks. Thus, PCH is a promising agent as an SFC in ESD of the esophagus. © 2012 American Society for Gastrointestinal Endoscopy.
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肺全摘手術術後の右心室負荷による催不整脈性に関する検討. Invited Reviewed
高瀬凡平, 東村悠子, 田中良弘, 服部秀美, 石原雅之, 濱部晃, 永井智雄.
Therapeutic Research 33 ( 11 ) 1616 - 21 2012
Language：Japanese Publishing type：Research paper (conference, symposium, etc.)
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Kishimoto S., Ishihara M., Kanatani Y., Nambu M., Takikawa M., Sumi Y., Nakamura S., Mori Y., Hattori H., Tanaka Y., Sato T.
Journal of Tissue Engineering 2 ( 1 ) 1 - 8 2011.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Tissue Engineering
Low-molecular-weight heparin/protamine microparticles (LH/P MPs) serve as carriers for controlled release of heparin-binding cytokines. LH/P MPs were stably coated onto plastic surfaces by drying. The purpose of this study is to evaluate a culture method for selective expansion of CD34+ cells using LH/P MPs as cytokine-binding matrix. Ficoll-purified mouse bone marrow cells (mouse FP-BMCs) containing CD34+ cells were cultured on LH/P MP-coated plates in the presence of stem cell factor (SCF), thrombopoietin (Tpo), and Flt-3 ligand (Flt-3) in hematopoietic progenitor growth medium (HPGM) supplemented with 4% heat-inactivated fetal bovine serum (FBS). After 8 days of culture, the total cell count increased 4.6-fold, and flow cytometry analyses revealed that 23.8% of the initial cells and 57.4% of the expanded cells were CD34 positive. Therefore, CD34+ cells were estimated to have increased 11.0-fold. In contrast, cultured CD34+ cells on uncoated tissue culture plates increased 5.8-fold in an identical medium. © The Author(s) 2011.
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キトサンの止血機序の解明 Reviewed
山崎敬子, 吉本怜子, 服部秀美, 田中良弘, 石原雅之.
防衛衛生 58 ( 11 ) 221 - 9 2011.11
Language：Japanese Publishing type：Research paper (scientific journal)
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Kumano I., Kishimoto S., Nakamura S., Hattori H., Tanaka Y., Nakata M., Sato T., Fujita M., Maehara T., Ishihara M.
Cellular and Molecular Bioengineering 4 ( 3 ) 476 - 483 2011.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Cellular and Molecular Bioengineering
Mixing a low-molecular-weight heparin (e.g., fragmin) with protamine results in the formation of waterinsoluble fragmin/protamine microparticles (F/P MPs) approximately 0.5-3 lm in diameter. In this study, we investigated the ability of F/P MPs to improve the viability of Lewis lung (3LL) cancer cells, B16 (B16) melanoma cells, and a human hepatoma (Huh7) cell line in a suspension culture, and the ability of F/P MPs to enhance tumor take rate and growth in vivo. F/P MPs rapidly bound to the surface of the cells. The interaction of the cells with F/P MPs induced formations of the tumor cell/F/P MP aggregates and maintained the viability of those cells in suspension for at least 3 days. The addition of F/P MPs with FGF-2 significantly enhanced the growth rate of the cells in a fetal bovine serum (FBS)-free medium. The tumor cell/F/P MP aggregates, which were subcutaneously injected into the backs of mice, significantly stimulated the formation and growth of subcutaneous tumors consisting of 3LL, B16, and Huh7 cells. Furthermore, the tumors produced by injection of 7.5 9 105 Huh7 into nude mice did grow only with F/P MPs. Thus F/P MPs can utilize as cell carrier for tumor cell transplantation. © 2011 Biomedical Engineering Society.