著者

岸田 晶夫

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.25, no.1, pp.27-34, 2018 (Released:2018-03-14)

参考文献数

13

被引用文献数

1

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近年,脱細胞化組織は組織再生のための移植材料として広く応用されている.脱細胞化組織は,生体組織から細胞成分を除去した三次元構造を有する細胞外マトリックスであり,種々の脱細胞化技術によって得られる.この調製法の違いが,得られる脱細胞化組織の形態や構造,力学的特性,生物活性に強く影響している.臨床でも広く試みられている脱細胞化組織の同所性移植は,細胞が浸潤してECMを再構築し,最終的に元の組織を再生させる.一方で,脱細胞化組織を異所性に移植した場合は,移植部位に適した組織が構築される場合と脱細胞化組織の由来となった組織が異所性に再構築される場合とがある.本稿では,脱細胞化生体組織の作成法,現在の状況および今後の動向について解説した.

著者

福嶌 五月 宮川 繁 澤 芳樹

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.23, no.2, pp.180-185, 2016 (Released:2016-08-31)

参考文献数

13

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Regenerative therapy by cell transplantation is the promising treatment for advanced cardiac failure. Therapeutic mechanisms underlying this treatment has been shown to be the paracrine effects, in which the transplanted cells induced a sustained upregulation of a variety of cytokines, predominantly proangiogenic cytokines, in the damaged cardiac tissue to enhance the native regenerative capacity and thus to yield the therapeutic effects. Considering the limitation in cell transplantation therapy, a “shelf-stored” drug, in any, which induce up-regulation of proangiogenic cytokines in the cardiac tissue, would be an ideal solution for widespread application of cardiac regeneration therapy. ONO-1301, which is a synthetic prostacyclin agonist with thromboxane A2 synthase inhibitory activity, has been shown to act as a multiple-cytokine inducer by ligating IP receptor expressed in the endothelial cells, vascular smooth muscle cells or fibroblasts. In addition, ONO-1301 is chemically stable compared to commercialized prostagrandin agonists, such as illoprost or beraprost, and therefore be promised as the drug for chronic pathologies. We developed polymerized form of ONO-1301, YS-1402, as a slow-releasing drug for treating advanced cardiac failure, In this review, we document pharmacological activity of ONO-1301/YS-1402, results of preclinical studies and protocol of following first-in-human investigator initiated clinical study.

著者

井上 悠輔

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.24, no.2, pp.135-141, 2017 (Released:2017-08-31)

参考文献数

10

被引用文献数

1

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Main points of ISSCR (The International Society for Stem Cell Research)’s amended guidelines of 2016 were summarized. The guidelines are presented as a single document based on the preceding two ISSCR guidelines, with a preamble that articulates core ethical principles for guiding both basic and clinical stem cell research: the integrity of the research enterprise, the primacy of patient welfare, respect for research subjects, transparency, and social justice. As they concern irreproducible results and the incomplete reporting of findings from preclinical studies, they strongly require rigorous demonstration of preclinical evidence and rigorous peer review of clinical trial protocols and study reporting.

著者

深井 原 藤堂 省

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.18, no.1, pp.92-98, 2011-06-10 (Released:2014-11-26)

参考文献数

19

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Heavy water, deuterium oxide(D2O), is a stable isotope compound of H2O, causing stabilization of actin and tubulin. D2O inhibits cytosolic calcium overload via plasma membrane channel and ER. D2O stimulates ATP production by augmenting glucose uptake, activities of glycolysis, TCAcylcle, and oxidative phosphorylation in certain experimental models. Further, D2O inhibits organ swelling and damage during cold preservation. Although precise mechanism remains unclear, these properties are considered suitable for the organ preservation. Here we reviewed the possible cytoprotective actions of D2O from the biophysical, biochemical, and clinical viewpoints to enlighten the new insight of organ preservation.

著者

西郷 健一 中岡 博史 早野 崇秀 Phuong Thanh NGUYEN 青山 博道 圷 尚武 北村 博司 丸山 通広 井ノ上 逸朗

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.30, no.1, pp.007-014, 2023 (Released:2023-02-21)

参考文献数

22

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Acute or chronic graft rejection is the primary threat to transplant recipients. The golden standard for rejection diagnosis is invasive biopsy. Measurement of donor derived cell free DNA (ddcfDNA) in the blood have been described as a non-invasive biomarker for organ transplantations. To develop a diagnostic system to detect graft injury before diagnosis by biopsy, we established capture-based sequencing procedure on extracted cf DNA which targets 1000 selected single nucleotide polymorphism sites. The ddcfDNA percentages were highly elevated on the first days after transplantation, but ddcfDNA percentages were decreased gradually within 7-14 days in stable patients with no sign of rejection. In 80% of cases having rejection episodes and all cases having biopsy proven rejection, ddcfDNA levels showed greater expressive signals on days of rejection episode. Additionally, we found evidences showing that ddcfDNA level sensitively corresponded with immunosuppressant dosages which were administered on recipients. This non-invasive method enables us close follow up the graft injury and prevent graft rejection.

著者

才田 大輔

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.29, no.2, pp.72-83, 2022 (Released:2022-08-08)

参考文献数

22

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我々は蛋白質構造解析に特化したアニーリング方式の量子コンピューターを検討している. この手法では, 蛋白質の折り畳みに寄与する生物化学的な作用を数理モデルに取り入れ, 量子ビット回路に直接実装する. 共に最小エネルギー状態に帰着するという観点で, 蛋白質の折り畳みと量子アニーリングのメカニズムは親和性が高いと考えている. 疾病の原因究明に踏み込むことができるような量子コンピューターの実現を目指している.

著者

山田 直也 唐澤 直義 高橋 将文

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.29, no.2, pp.128-132, 2022 (Released:2022-08-08)

参考文献数

21

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Ferroptosis is known to be implicated in various liver diseases; however, the liver-specific regulatory mechanism of ferroptosis is not fully understood. We identified 7-dehydrocholesterol reductase (DHCR7) as a novel regulator of ferroptosis in hepatocytes. DHCR7 inhibition suppressed ferroptosis in Huh-7 cells. The DHCR7 inhibition increased the accumulation of intracellular 7-dehydrocholesterol (7-DHC), a substrate for DHCR7, and extrinsic 7-DHC supplementation suppressed ferroptosis. We assessed that oxidation of 7-DHC compensatory prevents cellular membrane lipid peroxidation related to ferroptosis. DHCR7 inhibitor also suppressed ferroptosis in murine primary hepatocytes and hepatic ischemia-reperfusion injury in mice. These findings suggest that targeting DHCR7 is a potential therapeutic strategy for ferroptosis-related liver disease.

著者

福嶌 教偉 藤田 知之 小川 真由子 北村 惣一郎

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.24, no.1, pp.29-36, 2017 (Released:2017-03-31)

参考文献数

12

被引用文献数

1

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After the world first use of fresh aortic valve homografts transplanted into the descending thoracic aorta was reported in 1956, preservation methods have been investigated and the cryopreservation technique is currently used worldwide. In early 1990s, the cryopreservation technique for homograft was introduced to Japan and the local heart valve bank was established in Nara. Although organ procurement has been regulated by The Organ Transplantation Act (brain-dead donors since 1997, donors after cardiac death since 1979), there has been no law or governmental procurement network (except for cornea) in Japan. Since the late 1980s, some university hospitals have developed original banks. Finally, in 2001 guidelines for tissue procurement were established by The Japanese Society of Tissue Transplantation and Japan Tissue Transplant Network (JTTN) to coordinate tissue harvesting. Five tissue banks were joined to the tissue transplant network (skin in one, heart valves in two, and bone in two). In 2016, homograft implantation surgery was finally covered by insurance and the number of these surgery will increased in near future.

著者

安藤 由典

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.24, no.1, pp.7-12, 2017 (Released:2017-03-31)

参考文献数

30

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Allogeneic islets are transplanted to many type 1 diabetic patients in the world in recent years. But that situation is limited by the short supply of donner islets, and the recipients must continuously use immunosuppressive agents which may have deleterious effects on the islets. In order to resolve these problems, we can use the bioartificial pancreas (BAP) which can separate xenogeneic or allogeneic cells from the immune system cells of the recipients. So many basic reseach and animal examinations about various types of BAP have being examined to this date. Recently, clinical trials have started on several BAP. The purpose of this review is to show the current status of clinical trials about the BAP.

著者

種市 尋宙

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.26, no.2, pp.113-119, 2019 (Released:2019-09-26)

参考文献数

8

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2010年7月にわが国における臓器移植法が改正されたが, いまだに深刻な課題が存在しており, 引き続き活動をしていくことが重要である. 本稿では, 小児臓器提供における問題と終末期医療について詳述する. 海外渡航, ドナー不足, 虐待評価, 未熟な終末期医療などが具体的な問題点として存在し, いずれも解決されなくてはいけない. そのためには, まずわれわれが問題と対峙し, 議論を深めていく必要がある.

著者

松村 外志張

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.28, no.2, pp.94-112, 2021

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<p>臓器移植などの医療目的や基礎研究ならび産業利用のための人体臓器, 組織, 細胞(以下ヒトモノ)の重要性は急速に高まり, かつ実験技術の飛躍的な進歩はヒトモノが有する生命性を拡大し新たな問題を生み出している. わが国においても, 臓器移植法の改正等, 部分的な取組みはなされてはいるものの, 全体としてみるとき, 自給体制の整備が遅れ, 移植治療の機会の逸失や研究資源を海外からの恵与に依存する状態が続いている. このことがヒトモノという概念を顧慮する機会を逸し, 社会的な整備の遅れを招いていると考えられる. 筆者はこれまでヒトの培養細胞を用いて基礎研究や産業応用を行って来た中で, 出発素材となるヒトの臓器·組織の供給面の検討なくして研究開発は完結しないとの強い信念を抱いてきた. 本稿では, ヒトモノとは何か, そして社会の中でのヒトモノの位置付けを論じた上で, ヒトモノにまつわる問題の解決を目指して, 法規の背景をなす倫理原則をあらためて検討した. 過去の非倫理的な人体実験に対する反省に端を発し, その結晶ともいえるベルモント報告書の倫理原則3ヶ条, すなわちヒトへの敬意原則, 仁恵原則, 正義の原則を尊重することを基本とする. ここで新たに, 敬意原則に「ヒトモノへの敬意」を含め, 正義原則に「ヒトモノの取扱い目的による差別をしない」ことを含める. さらに, ヒトモノを生物多様性に関する国際条約の対象として保護ならびに監視することを第4原則に, そしてヒトモノに対する所有権を認めず, 社会的な求めに応じて加えた加工による付加価値を除き, 授受に利益を付加しない無償性原則を第5原則として付け加えた. これら5ケ条の倫理原則を担保するためには, 必ずしも新たな法規の制定を必要としない部分もあると考えられるが, 制定が不可避な部分もあると考えヒトモノ基本法私案として, いくつかの考えられる方策とともに提案した. ヒトモノ基本法の制定は, わが国におけるヒトモノ取扱いの先進性を世界に宣言し, 今後時間を掛けて現行法規の調整を順次進めることによって, 国内問題を解決に導くとともに, 国際的な協力の輪に入る機会につながるものと期待する.</p>

著者

水野 満 関矢 一郎

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.26, no.2, pp.153-161, 2019 (Released:2019-09-26)

参考文献数

23

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The wonderful discoveries in basic research are leading to practical use as “Cellular and Tissue-based Products” in Japan. However, in order to safely deliver living cells to the clinical field of medicine, development of transport and preservation technology is essential. In this review, we introduce approved products as an example, show what kind of preservation method is adopted, and report on the verification results of the preservation method of the products currently under development.

著者

高橋 公太

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.18, no.1, pp.11-32, 2011-01-10 (Released:2013-11-26)

参考文献数

27

被引用文献数

1

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It has now been over 20 years since we performed our first ABO-incompatible kidney transplantation(ABO-IKTx)in Japan. During that time about 1700 ABO-IKT have been performed. Since 2001 the success rate for these kidney transplants has been 96% for 1-year graft survival and 91% for 5-year graft survival, similar to results for ABO-compatible KTx. This dramatic improvement in results means that this transplantation procedure has become accepted for curative therapy in end-stage renal failure. Today ABO-IKTx accounts for 30% of all living KTx performed in Japan.In the 100 years since Karl Landsteiner discovered human ABO blood groups, the common wisdom has been that organ transplantation between incompatible blood groups would result immediately in hyperacute rejection and graft loss. However, this concept turned out to be a completely unsupported assumption. We provided epidemiological proof that hyperacute rejection was not caused by the ABO histo-blood group antigens(ABO HBGAS).We have reported elsewhere our two new ground-breaking findings regarding ABO-IKTx. We are confident that these findings will overturn the conventional wisdom about ABO-IKTx, and will mark a fundamental change in treatment strategies.The first finding involves ABO HBGAS, which are classed as carbohydrate antigens.Conventionally, emphasis has been placed on the saccharide chains only, and related phenomena have been interpreted accordingly. However, the saccharide chains in ABO histo-blood group antigens are present in the form of glycoproteins, and the binding proteins are termed " carrier proteins ". By employing proteomic analysis, we discovered that these binding proteins differ between the ABO HBGAS on the erythrocytic surface and those on the vascular endothelial cell surface. These new facts make it necessary to divide the ABO HBGAS into two broad categories.The antigens on the erythrocyte surface are ABO blood group antigens, while the antigens on the vascular endothelial cell surface are ABO histo group antigens.The lymphocytes probably do not identify the saccharides and binding proteins separately, but instead recognize them as part of a whole, and then proceed to form antibodies that have a high affinity for that whole. In other words, the recipient's anti-A/anti-B natural antibodies are primarily anti-ABO blood group antibodies, which do not have much affinity for the ABO histo group antigens on the vascular endothelial cell surface in the transplant organ. This is the main reason that hyperacute rejection is not induced by ABO incompatibility. The second finding relates to the known fact that ABO-incompatibility associated acute antibody-mediated rejection is caused by anti-A/anti-B antibodies. Conventionally it had been believed that this rejection response was caused by natural antibodies present in the recipient. However, if we consider the first theory, it becomes clear that the antibodies eliciting acute antibody-mediated rejection could not be produced without transplantation of the donor organ. That is to say, the recipient lymphocytes must be sensitized to the ABO histo group antigens on the vascular endothelial cells, resulting in the new production of anti-A/anti-B de novo antibodies. We have proven this fact indirectly elsewhere.After considering the new findings described above, we have established pretransplant desensitization therapy as the cornerstone of our transplantation treatment strategy.

著者

白木 公康

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.28, no.1, pp.9-17, 2021 (Released:2021-02-10)

参考文献数

21

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The characteristics of COVID-19 infection consist of the characteristics of both influenza caused by infection-induced cytokines and varicella caused by cell-mediated immunity to the virus. An indicator of the therapeutic efficacy of anti-herpetic drugs in herpes zoster is the cessation of new lesions rather than the improvement of inflammation. Inflammation due to cell-mediated immunity reaches its peak 3 days after antigen contact in lacquer dermatitis. Therefore, the inflammation due to cell-mediated immunity in herpes zoster worsens for 3-5 days due to the persistent presence of the virus even after the start of antiviral treatment. It is a characteristic of COVID-19 pneumonia that Avigan (favipiravir) treatment is effective but that the inflammation of COVID-19 pneumonia continues to worsen for 3-5 days even after Avigan treatment.

著者

小原 弘道

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.28, no.2, pp.157-158, 2021 (Released:2021-07-29)

参考文献数

1

著者

小林 英司

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.22, no.2, pp.251-252, 2015-07-10 (Released:2016-04-01)

著者

川村 知裕 桃實 徹 舟木 壮一郎 別所 俊哉 新谷 康 井上 匡美 南 正人 中尾 篤典 奥村 明之進

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.22, no.2, pp.117-120, 2015-07-10 (Released:2016-04-01)

参考文献数

8

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Because hydrogen provides potent antioxidative eff ects against acute lung injury, we hypothesized that treatment of organ donors with hydrogen during mechanical ventilation would reduce graft injury after lung transplant. Orthotopic left lung transplants were performed using an allogeneic rat model. Donors were exposed to mechanical ventilation with 98% oxygen plus 2% nitrogen or 2% hydrogen for 3 hours prior to harvest and the lung grafts underwent 4 hours of cold storage. The combination of mechanical ventilation and cold ischemia resulted in marked deterioration of gas exchange when the donors were ventilated with nitrogen, which was accompanied by upregulation of proinfl ammatory cytokines. These lung injuries were significantly attenuated by ventilation with hydrogen. Hydrogen induced heme oxygenase (HO)-1 in the grafts prior to implantation, which may contribute to protective eff ects aff orded by hydrogen. Hydrogen inhalation during ventilation prior to organ procurement eff ectively protected lung grafts from ischemia/reperfusion injury.

著者

小林 英司

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.26, no.1, pp.68-69, 2019 (Released:2019-03-29)

著者

杉山 健太郎 磯貝 和也 坂爪 重明 外山 聡 佐藤 博 齋藤 和英 中川 由紀 田﨑 正行 高橋 公太 平野 俊彦

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.18, no.1, pp.47-51, 2011-06-10 (Released:2014-11-26)

参考文献数

10

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Renal transplant recipients are administered immunosuppressive therapy to prevent acute rejection. In particular, new immunosuppressive agents have helped to improve the allograft survival rate and reduce the rate of rejection in renal transplant recipients. The optimal dose of calcineurin inhibitors is determined by therapeutic drug monitoring. However, the pharmacological efficacy of cyclosporine and tacrolimus should be estimated using both pharmacokinetics and pharmacodynamic parameters. We therefore employed the lymphocyte immunosuppressant sensitivity test(LIST) with the 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide(MTT)assay procedure to evaluate renal transplant recipients. The LIST with the MTT assay procedure can predict the pharmacological efficacy of immunosuppressive drugs using peripheral blood mononuclear cellsMoreover, renal transplant recipients must be correctly treated with immunosuppressive agents and another medicines. Therefore, the pharmacist must provide instructions for all medications to maintain adherence in renal transplantation. Therefore, transplantation therapy must be based on the pharmaceutical care given by pharmacists.

著者

和田 恭一

出版者

一般社団法人 日本臓器保存生物医学会

雑誌

Organ Biology (ISSN:13405152)

巻号頁・発行日

vol.24, no.1, pp.13-19, 2017 (Released:2017-03-31)

参考文献数

11

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One year-mortality of end-stage heart failure is about 50%, which is comparable to those of terminal cancers. Recently, new curriculum for specialists of clinical pharmacology for chemotherapy of cancer has been released. Likewise, we need to create specialized clinical pharmacists for the management of end-stage heart failure.These pharmacists will be called as “Transplant Pharmacist”. In this article, we will outline our effort as the special team for the management of the patients waiting for heart transplant and the post-heart transplant patients. Transplant pharmacists will play a pivotal role in this team activity. Prevention of thromboembolism in the patients with left ventricular assist device (LVAD) needs close therapeutic drug monitoring (TDM) and rapid feedback of data on warfarin. In addition to these actions, successful management of warfarin requires that the transplant pharmacists effectively counsel and educate these patients with LVAD. TDM of antibiotic drugs is also essential for treatment of infection with LVAD. On the other hand, immunosuppressant like cyclosporine, tacrolimus, mycophenolate mofetil and evelolimus have critical influence on graft rejection as well as susceptibility to infection. Transplant pharmacists should evaluate effective the plasma concentration of those drugs through Parmacokinetics/Pharmacodynamics (PK/PD). Immunosuppressant adherence is also a critical issue to heart transplant recipient. Therefore, constant counseling and educating to these patients from transplant pharmacists are necessary.Transplant pharmacists skilled at PK/PD and TDM of cardiovascular, antibiotic and immunosuppressive drugs would be key talents in highly-sophisticated medicine in the future.