Organ Biology
Online ISSN : 2188-0204
Print ISSN : 1340-5152
ISSN-L : 1340-5152
23 巻, 2 号
選択された号の論文の24件中1~24を表示しています
  • 編集委員会
    2016 年 23 巻 2 号 p. 92-95
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
  • 近藤 丘
    2016 年 23 巻 2 号 p. 97-102
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Since Japanese first lung transplantation from donor after brain death (DBD) in 2000, where University Hospitals of Osaka University and we Tohoku University shared right and left lobes, I experienced 73 cases of DBD lung transplantation. Among them, I describe here seven memorable cases; first DBD lung transplantation, fatal infectious complication after transplantation, first case of pulmonary arterial hypertension, dense adhesion in case of lymphangioleiomatosis, replacement of pulmonary arterial trunk, first case after disastrous East Japan earthquake, and retransplantation. Although the annual number of operation was five to six, I could spend impressive last ten years in University life.
  • 伊藤 暢
    2016 年 23 巻 2 号 p. 103-110
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    The liver plays a central role in metabolism, detoxification and maintenance of systemic homeostasis and is well known for its highly remarkable regenerative capacity in response to various types of injury. Hepatocytes, the parenchymal cells in the organ, constitute a continuous epithelial lining together with biliary epithelial cells. While putative stem/progenitor cells that possess a bi-lineage differentiation potential to hepatocytes and biliary epithelial cells have long been postulated, there is still an ongoing debate regarding their presence and exact contribution to the regenerative process. In the meantime, much evidence has been accumulated showing an unprecedented level of phenotypic plasticity between hepatocytes and biliary epithelial cells, in that these differentiated cells can undergo bi-directional conversion under injury conditions. Here, I briefly introduce recent progress in the understanding of the cellular basis for liver regeneration in view of a lineage relationship between liver epithelial cells, as well as our own findings demonstrating a hitherto unrecognized structural plasticity of the biliary epithelial tissue that may play a fundamental role in liver regeneration.
  • 西塚 哲, 片桐 弘勝, 鈴木 悠地, 高原 武志, 新田 浩幸, 滝川 康裕, 佐々木 章
    2016 年 23 巻 2 号 p. 111-116
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    The mechanisms of liver regeneration remain unclear. Graft genotyping from living donor liver transplantation revealed the involvement of extrahepatic cells in liver regeneration. The transplantation of bone marrow-derived multilineage differentiating stress enduring (Muse) cells after physical partial hepatectomy in mice showed that Muse cells accumulated adjacent to the physically damaged lesion and subsequently differentiated into hepatocytes, cholangiocytes, and sinusoidal epithelial cells, suggesting that Muse cells can be of a candidate of extrahepatic cells involved in the liver regeneration. Muse cells can be effectively isolated as stage-specific embryonic antigen-3- (SSEA-3) positive from human bone marrow-derived mesenchymal stem cells, and demonstrated pluripotency that can differentiate the endodermal, ectodermal, and mesodermal cells. In contrast to other stem cell resources, Muse cells do not require gene transfection for the acquisition of the pluripotency and do not form tumors in vivo. These characteristics minimize ethical concerns in human cellular transplantation. Together with the characteristics of Muse cells, our results suggest that Muse cells may aid in liver tissue repair and regeneration after physical partial hepatectomy in humans.
  • 佐野 元昭
    2016 年 23 巻 2 号 p. 117-120
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Early application of therapeutic hypothermia, rapid achievement of target cooling temperature were key factors for improving survival and neurological outcomes. In the present situation, targeted Temperature Management (TTM) is applied to only a minority of post-cardiac arrest patients. We have been looking forward to seeing widely applicable therapeutic approaches. We previously demonstrated that both inhalation of 2% hydrogen gas and TTM (33°C), starting at the beginning of cardiopulmonary resuscitation and given for 2 hours after return of spontaneous circulation (ROSC), yielded comparable improvement in survival and neurological deficit after ROSC in a rat model of cardiac arrest. However, in a clinical setting, hypothermia is applied after ROSC. We have confirmed that the benefit of hydrogen inhalation is similar when begun after ROSC.
    We would like to emphases a salutary effect of hydrogen gas inhalation on the neurological outcome after cardiopulmonary resuscitation independently of TTM in rats. Inhalation hydrogen gas therapy, either alone or in the combined with TTM, could represent a promising strategy to improve brain resuscitation for post cardiac arrest patients in the near future.
  • 陳 豊史, 近藤 健, 土屋 恭子, 伊達 洋至
    2016 年 23 巻 2 号 p. 121-125
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Severe donor shortage is one of the most critical issues in lung transplantation. To overcome this grave problem, it is essential to use the marginal donor lungs, which might be injured and are not appropriate for safe lung transplantation. Ex vivo lung perfusion (EVLP) was developed to evaluate such donor lungs objectively before lung transplantation. In Kyoto University, we also established EVLP in small and large animals to evaluate lung function and even to treat the injured lungs using EVLP. Unlike other organs, transalveolar administration (inhalation or nebulization) corresponds to a drug delivery route specific to the lung. Therefore, we considered the drug inhalation during EVLP to recondition and treat the injured donor lungs. In a small animal EVLP, isoflurane, ß2-adrenoreceptor agonist, and phosphodiesterase III inhibitor showed a protective effect against the pulmonary ischemia-reperfusion injury. Furthermore, we also found that ß2-adrenoreceptor agonist had a protective effect on the injured lungs in a large animal EVLP. In conclusion, we demonstrated that transalveolar drug administration was effective and useful for the treatment of the injured lungs during EVLP.
  • 伊藤 泰平, 剣持 敬, 會田 直弘, 大島 稔, 大野 慎一郎, 西川 徹, 鈴木 敦詞, 長谷川 みどり, 日下 守, 浅野 武秀, 星 ...
    2016 年 23 巻 2 号 p. 126-130
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Pancreatic graft thrombosis is the primary cause of non-immunologic graft loss, with an incidence ranging from 5% to 15%. Therefore, developing a screening test to detect graft thrombosis after pancreatic transplantation is important. We created a screening test to assess graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography (CEUS) with Sonazoid. A total of seven patients were examined using CEUS after undergoing pancreatic transplantation. All patients were observed to have a clear blood flow in the splenic vein in the pancreatic graft, while only one of the seven patients exhibited a blood flow in the horizontal portion of the splenic vein on Doppler ultrasonography performed immediately after pancreatic transplantation. CEUS with Sonazoid demonstrated the blood flow in the splenic vein and parenchyma of the pancreatic graft in detail, in spite of the slow and lateral blood flow in the splenic vein of the pancreatic graft immediately after transplantation.
    Evaluation of tissue blood flow in pancreatic graft using ΔTp(V-P) calculated by time intensity curve as shown by CEUS correlates with endocrine function of pancreatic graft 1 month after transplantation. These findings suggest that CEUS should become one of the novel and useful examination for pancreas transplantation.
  • 片桐 弘勝, 西塚 哲, 鈴木 悠地, 高原 武志, 新田 浩幸, 滝川 康裕, 佐々木 章
    2016 年 23 巻 2 号 p. 131-135
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Bone marrow mesenchymal stem cells (BM-MSCs) have been considered to be a potential cellular source for liver regeneration among extrahepatic cells. Genotyping of human living donor liver transplantation revealed that cells derived from recipients differentiated into multiple types of liver cells, suggesting that extrahepatic as well as pluripotent cells contributed to the liver regeneration. We chose to examine a unique type of stem cell in human BM-MSCs, the multilineage-differentiating stress-enduring (Muse) cells, as extrahepatic/BM-derived cells for liver regeneration because they demonstrate pluripotency during tissue repair. Both Muse and non-Muse fractions were isolated from human BM-MSCs and separately transplanted into SCID mice with partial hepatectomy. We found that transplanted Muse cells differentiated into cells positive for HepPar-1, CK7, Lyve-1, and CD68, and both albumin and antitrypsin of human origin adjacent to the damaged site. In contrast, the non-Muse cells did not show the same lineage of differentiation. These results suggest that a distinct type of extrahepatic cells, BM-Muse cells, exclusively contributes to the regeneration of various cell types of the liver. Thus, the application of BM-Muse cells could be an effective therapy.
  • 石田 伸樹, 石山 宏平, 平田 文宏, 佐伯 吉弘, 田中 友加, 大段 秀樹
    2016 年 23 巻 2 号 p. 136-140
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    In a mouse model, we have previously shown that liver natural killer (NK) cells play a pivotal role in islet graft loss during the early phase after intraportal islet transplantation. To modulate the activation of liver NK cells after islet transplantation, we focused on mesenchymal stem cells (MSCs), which have been reported to have immunosuppressive effects, and we studied the immunomodulatory effects of MSCs on liver NK cells. In this study, we have confirmed that MSCs suppress the activation of liver NK cells after intraportal islet transplantation.
  • 矢吹 皓, 渡邉 龍秋, 菊地 正史, 野津田 泰嗣, 新井川 弘道, 松田 安史, 野田 雅史, 桜田 晃, 星川 康, 船橋 淳一, 岡 ...
    2016 年 23 巻 2 号 p. 141-144
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Mycophenolate mofetil (MMF) has been used as a standard immunosuppressive agent after lung transplantation. MMF is rapidly metabolized to active constituent, mycophenolic acid (MPA), after intake. Gastrointestinal side- effects and leukocytopenia are common adverse effects of MMF. Although, therapeutic drug monitoring (TDM) for calcineurin inhibitors is widely used, the role of TDM for MPA is unclear in lung transplantation. We investigated the correlation among the blood concentration of MPA, the dosage of MMF and the number of leukocyte in lung transplant recipients. The correlation coefficient between the blood concentration of MPA and the dosage of MMF was not significant, so MMF might require TDM. On the other hand, neither the correlation coefficients between the number of leukocyte and the blood concentration of MPA nor the correlation coefficients between the number of leukocyte and the dosage of MMF were not significant. Further investigation is necessary to find the meanings of TDM for MPA after lung transplantation.
  • 岩本 整, 今野 理, 木原 優, 横山 卓剛, 小澤 陽介, 中村 有紀, 河地 茂行, 竹内 祐紀
    2016 年 23 巻 2 号 p. 145-149
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    There are few papers on high risk cytomegalovirus (CMV) donor-positive /recipient-negative (D+/ R-) and ABO-incompatible kidney recipients. A retrospective study was performed in CMV high risk for ABO-incompatible kidney recipients at our center. We analyzed effectiveness of prophylactic therapy using valganciclovir (VGCV) for 3 months after transplantation for the cases described above.
    We evaluated 11 CMV high risk kidney transplant cases between February 2010 and September 2015. The subjects were divided into two groups which are ABO-compatible group (ABO-C, n=5) and ABO incompatible group (ABO-I, n=6). The incidence of CMV infection which required treatment, timing of change from seronegative to seropositive were compared. CMV antibody status was follow up until the end of the first year of posttransplantation.
    Our immunosuppressive regimen for ABO-I cases was a combination of calcineurin inhibitors (tacrolimus/cyclosporine), methylprednisolone, mycophenolate mofetil, basiliximab (POD 0 and POD 4), and Rituximab which is given 14 days before transplantaion. Three patients (60%) developed CMV infection in ABO-C group., Four patients (66.7%) developed CMV infection in ABO-I group. Three patients (60%) acquired CMV serepositive in ABO-C group. Those Three patients acquired seropositive after CMV infection. Four patients (66.7%) acquired CMV serepositive in ABO-I group. On the other hand, two patients acquired seropositive even without CMV infection in ABO-I group.
    Our study supports the benefit of the prophylactic therapy in CMV high risk and ABO-I recipients who was administered anti-CD 20 antibody.
  • 本間 真人
    2016 年 23 巻 2 号 p. 150-153
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Ministry of health, labour and welfare of Japan is promoting the use of generic drugs in the DPC (diagnosis procedure combination) hospitals including medical institutions dealing with organ transplantation. Immunosuppressive agents of which blood concentration monitoring is recommended to optimize the individual dose in the transplant recipients are also required to substitute from original bland to generic one, even though their pharmacokinetics are not equal. In this paper, author describes several issues for generic substitution for immunosuppressive agents in the pharmacokinetic points of view. The ESOT (Europian Society Organ Transplantation) guideline for the generic substitution of immunosuppressive agents is also presented to discuss the proper use of the generic drugs for transplant recipients in Japan.
  • 田原 裕之, 井手 健太郎, 大段 秀樹
    2016 年 23 巻 2 号 p. 154-157
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Xenotransplantation using pig donors provides a potential solution to the shortage of donors in organ transplantation. Hyperacute rejection has been overcome by generating of GalT knockout pigs. However, it had been proven that delayed xenograft rejection (DXR) including deposition of antibodies against non-Gal antigens and acute vascular rejection with macrophage infiltration caused in GalT knockout pig to non-human primate organ transplantation model. In our department we have continued to analyse a mechanism of DXR. CD47-signal regulatory protein (SIRP) α inhibitory signaling is implicated in negative regulation of phagocytosis by macrophages. The rejection of porcine cells caused by human macrophages due to incompatibility of CD47 between pig and human. We have previously proven that this genetic induction of human CD47 on porcine cells led to preventing phagocytosis by human macrophages in vivo and in vitro model. On the other hand, we investigated xenogeneic antibody-mediated rejection against the non-Gal antigens which included N-Glycolylneuraminic acid epitopes (NeuGc) on porcine cells using CMAH-/- mice which were completely deficient in NeuGc. It was shown that CMAH-/- mice having NeuGc antibodies rejected the NeuGc-expressing syngeneic islets. It has beed reported that human CD47 transgenic pigs and GalT/CMAH double knouckout pigs were recently produced. If DXR will be overcome, xenotransplantation might be acceptable for clinical application in near future.
  • 岩崎 研太, 小林 孝彰
    2016 年 23 巻 2 号 p. 158-161
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Accommodation has been termed as a condition without graft rejection even in the presence of anti-donor antibody, and which has been observed in xenotransplantation as well as ABO-incompatible organ transplantation. Depleting of antibody that would cause rejection of a graft could be always considered to acquire the resistant of a graft to immune-mediated injury. However, since removing all of antigen from graft cells is an unrealistic, to understand the accommodation is the important topic in organ transplantation. To investigate the mechanism how accommodation being achieved, xenotransplantation might offer a useful and incisive models. This review focus the histological finding of accommodation research in xenotransplantation field, and emphasize recent advances and important questions on HLA/ABO-incompatible transplantation.
  • 五十嵐 康宏, 猪村 梢, 柏山 浩, 猪村 武弘, 後藤 めぐみ, 稲垣 明子, 末田 輝子, 笠井 憲雪, 小野 文子, 後藤 昌史
    2016 年 23 巻 2 号 p. 162-163
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Development of the treatment for type I diabetes is an important and urgent mission. Large animal experimental models that mimic human pathology are necessary to estimate the effectiveness and safeness of the treatment under preclinical investigation phase. We report here our experience of clinical-grade streptozotocin-induced diabetes of cynomolgus monkey.
  • 陳 豊史, 本山 秀樹, 土屋 恭子, 高萩 亮宏, 齊藤 正男, 田中 里奈, 宮本 英, 大畑 恵資, 高橋 守, 近藤 健, 青山 晃 ...
    2016 年 23 巻 2 号 p. 164-167
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    To overcome the severe donor shortage in lung transplantation, it is crucial to use the marginal donor lungs and lungs from cardiac-death donors, which are supposed to be actually or potentially damaged. To utilize these damaged donor lungs safely, it is important to evaluate such donor lungs objectively before lung transplantation. Recently, ex vivo lung perfusion (EVLP) was developed and has been introduced internationally. Several clinical trials are also ongoing in Europe and North America. In this situation, we also established EVLP in small and large animals. Then, we have investigated the quality of donor lungs using EVLP and tried to treat the donor lungs during EVLP before lung transplantation. We also established several injured lung models and performed various experiments using EVLP, proving that damaged donor lungs could be treated with several drugs using EVLP. Furthermore, we investigated the detection of the regional lung damage using thermography. Herein, we demonstrated our findings and discussed the future of EVLP.
  • 尾崎 倫孝, 芳賀 早苗
    2016 年 23 巻 2 号 p. 168-172
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    We have been investigating the mechanism of liver regeneration and injury for liver surgery and transplantation. We firstly studied, in normal liver, the central role of IL-6/Jak/STAT3 in post-PH mitotic response and protective mechanism from hepatocyte injury, and the essential role of PDK1/Akt in post-PH cell growth in case where mitotic response is impaired. In fatty liver, reduced expression of p62/SQSTM1 plays a crucial role in post-hepatectomy acute injury and delayed regeneration with enhanced oxidative stress- and death signal-mediated injury. Reduced expression of p62/SQSTM1 lead to FasL/Fas overexpression and suppressed antioxidant genes through Nrf-2 inactivation, which along with the hypo-responsiveness of Akt, caused post-hepatectomy necrotic/apoptotic liver injury and delayed regeneration. Our study importantly suggests the potential role of p62/SQSTM1 in protecting the liver from all kinds of injury, providing pro-survival property to hepatocytes/liver. Here, we report the pivotal roles of p62/SQSTM1 as a key player for cell/organ preservation, and the potential application for liver preservation and transplantation.
  • 深井 原, 島田 慎吾, 小林 希, 石川 隆壽, 梅本 浩平, 大谷 晋太郎, 山下 健一郎, 嶋村 剛, 武冨 紹信
    2016 年 23 巻 2 号 p. 173-179
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Cellular survival and death during cold storage and hypothermic perfusion are regulated by intracellular signal, however, precise mechanisms remain elusive. Although the effector proteins of cellular fate work actually during 6 to 24 hours after rewarming and reoxygenation, the triggering events have already been regulated during organ procurement, transportation, and implantation before reperfusion. In this review, we summarize some potential mechanisms of regulating intracellular signals, mainly focused on the energy production and post-translational regulation under hypothermic conditions.
    A chaperon protein, 14-3-3ζ, regulates over 200 of the protein activity by covering the phosphorylation site within a 14-3-3 binding motif. Sirtuins also regulates many proteins directly and indirectly relates to the cell survival and death under some difficult conditions including cold and/or hypoxic insults. Sirtuins regulate many mitochondrial proteins primarily by deacetylation instead of ATP consuming processes. Further, sirtuins and 14-3-3s interact each other and sharing some target proteins, especially relating energy production and mitochondrial functions. Although these facts have been reported in ectotherms, hibernators, to human, little is known about its role in organ preservation, perfusion, and transplantation. Here, we reviewed its potential significance for the future research in the field of organ repair.
  • 福嶌 五月, 宮川 繁, 澤 芳樹
    2016 年 23 巻 2 号 p. 180-185
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    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.
  • 穴澤 貴行, 岡島 英明, 岩永 康裕, 増井 俊彦, 伊藤 達雄, 多田 誠一郎, 山根 佳, 高折 恭一, 海道 利実, 上本 伸二
    2016 年 23 巻 2 号 p. 186-188
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Pancreatic islet transplantation is a minimally invasive therapy for type1 diabetes mellitus patients with severe hypoglycemic unawareness despite adequate insulin therapy. Result of recent clinical trials had revealed that short-term results were promising, however, function of the transplanted islets had been decreased over time. In Japan, a phase II clinical trial with type 1 diabetic patients for islet transplantation to evaluate the T cell-depleting antibody induction and TNF inhibition protocol is under investigation. Islet transplantation was conducted under the Act on the Safety of Regenerative Medicine, which went into effect in November 2014. The introduction of the regenerative medicine approach is expected to accelerate the development of cell transplantation to treat diabetes. In this review, we outline a current status of islet transplantation and the future prospects.
  • 坂本 典久, 猿田 克年
    2016 年 23 巻 2 号 p. 189-192
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
    Regenerative medical products are of increasing interest for repair or replacement of damaged or destroyed tissues, making the path for more patients with incurable diseases to be treated effectively. Expediting the development and facilitating the access to regenerative medicine, it is important to keep the balance between efficient provision of innovative therapies and appropriate steps to ensure safety and efficacy. While many countries have various regulatory frameworks for clinical trials and medical treatments, the Act on the Safety of Regenerative Medicine and the Revised Pharmaceutical Affairs Law (PMD Act, i.e., the Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, Regenerative Medical Products, Quasi-Drugs and Cosmetics) have been put into effect simultaneously in Japan since November 2014. The PMD Act defines “regenerative medical products” (including gene therapeutics and cellular products) discretely from pharmaceuticals and medical devices, enabling to give conditional and time-limited marketing authorization to those products. The Pharmaceutical Affairs Consultation on R&D Strategy at PMDA makes both sponsors and regulators to secure scientific sound discussion in order to accelerate the development of regenerative medical products with timely provision of safety and effectiveness.
  • 福嶌 五月, 宮川 繁, 澤 芳樹
    2016 年 23 巻 2 号 p. 193-195
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
  • Molecular Biology of the Cell(細胞の分子生物学)
    野口 洋文
    2016 年 23 巻 2 号 p. 196-197
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
  • 奥見 奥見
    2016 年 23 巻 2 号 p. 203
    発行日: 2016年
    公開日: 2016/08/31
    ジャーナル フリー
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