Japanese Journal of Transplantation
Online ISSN : 2188-0034
Print ISSN : 0578-7947
ISSN-L : 0578-7947
Volume 52, Issue 1
Displaying 1-14 of 14 articles from this issue
  • Kenji OSAFUNE
    2017 Volume 52 Issue 1 Pages 001-006
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    The directed differentiation of human-induced pluripotent stem cells (hiPSCs) into clinically useful cell types has been vigorously examined. Transplantation methods and therapeutic potentials of hiPSC-derived cells have also been evaluated using animal disease models. Episomal vectors were successfully used to generate iPSCs without the use of viral vectors, which may cause cancer by damaging the genome. An iPSC stock derived from voluntary HLA homozygous donors is being prepared for use in regenerative therapy. These efforts have led to the start of clinical trials for the transplantation of hiPSC-derived retinal cells in Japan. Further research on reconstruction methods for functional tissues and organs from hiPSCs would resolve the problem of donor shortage in organ transplantation as well as accelerate regenerative medicine.

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  • Hitomi NISHINAKAMURA, Takeshi ITOH, Shohta KODAMA
    2017 Volume 52 Issue 1 Pages 007-012
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    Pancreatic islet regeneration is a major highly competitive research field in regenerative medicine. One reason why the field is so competitive is that the target cells, the pancreatic islet cells that secrete insulin, are easy to experimentally evaluate for a sophisticated model of transplantation.
    Induced pluripotent stem (iPS) cells are strong candidates for pancreatic islet cell regeneration. However, the theoretically regenerated islets induced from type 1 diabetes patients may have persisting unsolved pathogenesis such as autoimmune reactivity. As for present clinical options, the severe "type 1 diabetic" patients, whose levels of endocrine insulin, which induces life-threatening hypoglycemia, are negative, have few choices for replacement therapies.
    Pancreatic organ and islet transplantations are final options for these T1D patients. Islet transplantations have never been covered by medical insurance in Japan, but pancreatic organ transplantation have. Basically, islet transplantation is a cell therapy that could expand applications to such methods as porcine xenografts. To solve the problem of a shortage of donors, the usage for porcine islets is an extremely attractive challenge. Furthermore, bioartificial islets consisting of porcine islets with encapsulation would arise as an additional option for clinical transplantation. Lastly, as one approach to chronic pancreatitis, islet autotransplantations have been carried out in Japan without coverage by medical insurance. Because alcohol-induced patients are dominant in Japan, the backgrounds of patients suffering with pancreatitis here are entirely different from other countries.

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  • Kei MATSUMOTO, Takashi YOKOO
    2017 Volume 52 Issue 1 Pages 013-019
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    We previously established that mesenchymal stem cells (MSCs) differentiate into functional kidney cells capable of urine and erythropoietin production, indicating that they may be used for kidney regeneration. Recently, we demonstrated the construction of urine excretion pathways in rats and pigs. Rat metanephroi or metanephroi with bladders (developed from cloacas) were transplanted into host rats. Histopathological analysis showed that tubular lumina dilation and interstitial fibrosis were reduced in kidneys developed from cloacal transplants compared with metanephroi transplantation. The host animal's ureter was then connected to the cloacal-developed bladder, a technique we call the "stepwise peristaltic ureter" (SWPU) system. The application of this system avoided hydronephrosis and permitted the cloacas to differentiate well, with cloacal urine being excreted persistently through the recipient ureter. The methods developed here further the research necessary to generate a transplantable kidney.
    On the other hand, one group showed that CRISPR-Cas9 multiplexability can be as high as 62, demonstrating the possibility that porcine endogenous retroviruses (PERVs) can be inactivated for clinical application in porcine-to-human xenotransplantation. Another group showed that treatment with the wearable artificial kidney (WAK) was well tolerated and resulted in effective uremic solute clearance and maintenance of electrolyte and fluid homeostasis.
    Either xenotransplantation, wearable artificial kidney, or our regenerative method might change dialysis technology and kidney regeneration therapy.

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  • Shigeru MIYAGAWA
    2017 Volume 52 Issue 1 Pages 020-023
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    Despite recent progress in the treatment of heart failure, it remains a life-threatening disorder worldwide, and its mortality is quite poor. In this situation, left ventricular assist device (LVAD) implantation and heart transplantation are gold standard therapy for severe heart failure despite some drawbacks, such as infection, in LVAD and donor shortage in heart transplantation. To overcome these problems in heart failure therapy, regenerative therapy using autologous cells, tissue implantation, or new drugs were introduced to the clinical situation. In this section, we want to present recent basic or clinical work in cell sheet technology with myoblasts or induced pluripotent stem (iPS) cells and discuss new treatment strategy for heart failure, including regenerative therapy and heart transplantation.

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  • Toshiyuki ADACHI, Susumu EGUCHI
    2017 Volume 52 Issue 1 Pages 024-030
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    Of the 40,000 people in Japan with liver disease, such as hepatocellular carcinoma and viral cirrhosis , 10,000 die annually because of severe liver failure. Although the only fundamental treatment of severe liver failure is liver transplantation, due to a lack of donors, only less than thirty percent of patients receive a donated liver. Recently, regenerative medicine is attracting attention as a new method to cope with a shortage of donors. Regenerative medicine of the liver related to vascular network construction and liver organization has been studied through various approaches, such as stem cell research, cell sheet engineering, and extra-cellular matrix (ECM). The stage of clinical application is now approaching.

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  • Hironobu WADA, Yuichi SAKAIRI, Ichiro YOSHINO
    2017 Volume 52 Issue 1 Pages 031-037
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    Human lungs are generally not believed to repair or regenerate, and regenerative medicine in the field of respiratory organs, especially lungs, is far behind in comparison with those of other organs. Regenerative medicine is defined as medicine that replaces or regenerates human cells, tissue, or organs to restore or establish normal functions. On the other hand, lung transplantation is a last resort for patients suffering from end-stage lung diseases, and more than 4,000 cases have been performed worldwide. However, the number of patients on the waiting list largely exceeds the number of available transplantable lungs because of a severe short supply of organ donors. Lung regenerative medicine may be a solution for the serious issue to restore injured lungs or to supply transplantable functional lungs. We herein describe lung restoration, lung growth, and lung regeneration, which are related to lung transplantation.

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Original Article
  • Kengo ASAMI, Akiko INAGAKI, Takehiro IMURA, Satoshi SEKIGUCHI, Keisei ...
    2017 Volume 52 Issue 1 Pages 038-050
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    【Objective】Recent studies suggest that decreasing oxidative stress is crucial to achieve successful islet transplantation. Thioredoxin-1 (TRX), a multifunctional redox-active protein, has been reported to suppress oxidative stress. Furthermore, it also has anti-inflammatory and antiapoptotic effects. In this study, we investigated the effects of TRX on early graft loss after islet transplantation.
    【Methods】Intraportal islet transplantation was performed for two groups of streptozotocin-induced diabetic mice: a control group and a TRX group. Moreover, TRX-transgenic (Tg) mice were alternately used as islet donors or recipients.
    【Results】The changes in blood glucose levels were significantly lower in the TRX group compared with the TRX-Tg donor and control groups (p<0.01). Glucose tolerance and the residual graft mass were considerably better in the TRX group. TRX significantly suppressed the serum levels of interleukin-1β (p<0.05), though neither antiapoptotic nor antichemotactic effects were observed. Notably, no increase in the 8-hydroxy-2'‐deoxyguanosine level was observed after islet infusion, regardless of TRX administration.
    【Conclusions】The present study demonstrates that an overexpression of TRX on the islet grafts is in sufficient to improve engraftment. In contrast, TRX administration to recipients exerts protective effects on transplanted islet grafts by suppressing the serum levels of interleukin-1β. However, TRX alone appears to be also insufficient to completely prevent early graft loss after islet transplantation. We therefore propose that a combination of TRX and other anti-inflammatory treatments represents a promising regimen for improving the efficacy of islet transplantation.

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  • Miyuki FURUSAWA, Hideki ISHIDA, Masayoshi OKUMI, Tomokazu SHIMIZU, Kaz ...
    2017 Volume 52 Issue 1 Pages 051-059
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    【Objective】Chronic antibody-mediated rejection (CAMR) is among the most important factors that affect the outcome of kidney allograft. de novo donor-specific anti-HLA antibodies (DSA) have been reported to be related to CAMR.
    However, it remains still unclear about the relationship between the characteristics of de novo DSA and CAMR.The aims of the present study were to (1) clarify the de novo incidence rate and (2) investigate the relationship between the characteristics of de novo DSA and CAMR in kidney transplant recipients
    【Methods】One hundred and forty-five patients who had undergone kidney transplantation from 2000 to 2015 were screened for HLA antibodies. They were detected by using Luminex single antigen beads (One Lambda Inc.) with LABScan 100.
    【Results】DSA after kidney transplantation were detected in 54 patients (37%), and de novo DSAs were demonstrated in 47 patients of these 54 (87%).
    In 47 patients with de novo DSA, 40 (85%) were found to have HLA-DQ DSA. Of these 40 patients, 32 (80%) were diagnosed with biopsy-proven acute AMR or CAMR 6 months or later posttransplant and 4 (12.5%) lost their kidney allografts.
    【Conclusion】De novo HLA-DQ DSA were detected more frequently compared with HLA-class I or -DR DSA in kidney transplant recipients with CAMR. Screening for HLA-DQ DSA after kidney transplantation seems favorable to obtain better long-term outcomes of kidney allografts.

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Case Report
  • Masafumi OHIRA, Ryoichi GOTO, Yasuyuki KOSHIZUKA, Toshiya KAMIYAMA, Ke ...
    2017 Volume 52 Issue 1 Pages 060-066
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    We report a 20-year-old man with congenital hepatic fibrosis (CHF) involved with autosomal recessive polycystic kidney disease (ARPKD). He was diagnosed as having ARPKD on the basis of renal dysfunction at the age of three. When he was 16, computed tomography (CT) revealed hepatomegaly and intrahepatic bile duct dilatation consistent with CHF. As his liver function gradually worsened, he was introduced to our liver transplant unit at 19 years old. He was registered for a transplant candidate on the national waiting list of deceased-donor liver transplantation (DDLT). Gradual exacerbations in liver and renal functions were then observed. When 20 years old, he received DDLT. The technique of the venous `jump-graft' from the superior mesenteric vein was applied because of a severely narrowed portal vein. Moreover, a veno-venous bypass was used to avoid renal venous congestion during the anhepatic phase. We successfully managed to preserve the renal function during the peri-transplant period by combination therapy with rapamycin and tacrolimus minimization. Although some reports of living-donor liver transplantation for ARPKD had been made, to our knowledge this is the first case of DDLT for an adult ARPKD in Japan.

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  • Takeo TOGO, Yasushi HOSHIKAWA, Hideki MITOMO, Tatsuaki WATANABE, Hirot ...
    2017 Volume 52 Issue 1 Pages 067-072
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    Although tacrolimus is widely used as an immunosuppressive drug after lung transplantations, there have been few reports on adverse cardiovascular events after lung transplantation. A 36-year-old female underwent a right single-lung transplantation for idiopathic interstitial pneumonia. Intravenous administration of cyclosporine was started just after the transplantation, and it was switched to oral tacrolimus on day 4. On day 10, she suffered from acute rejection and was treated with a dose of tacrolimus and an administration of methylprednisolone for 2 days. On day 12, after the ingestion of tacrolimus, she had chest pain, dyspnea and syncope. Electrocardiography showed ST elevation in the chest leads from V3 to V5 and troponin T rose to 0.114 ng/ml. Coronary angiography showed no stenosis, but it demonstrated a spastic change of coronary arteries after coronary injection of acetylcholine. The tacrolimus concentration on the day of the attack was 11.9 ng/ml, and 15.4 ng/ml and 19.6 ng/ml on the following 2 days, respectively, despite dose reduction: therefore it was suggested that tacrolimus was the factor of the angina attack. Since the next day, she has undergone mechanical ventilation to treat pulmonary edema caused by heart failure for 4 days. She has experienced no angina attacks thereafter and has been quite well for 2 years since the lung transplantation. In summary, we report a patient who suffered from vasospastic angina possibly caused by tacrolimus 10 days after lung transplantation. We should fully consider vasospastic angina a tacrolimus the side effect.

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  • Seiichi KAWABATA, Seisuke SAKAMOTO, Masaki HONDA, Koshi UCHIDA, Keita ...
    2017 Volume 52 Issue 1 Pages 073-080
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    The patient was an 18-year-old woman complaining of persistent epigastralgia. She had undergone an isolated intestinal transplantation at the age of 12 for pseudo-Hirschsprung's disease. Endoscopy through the stoma revealed diffuse involvement of the distal part of the graft intestine, which had ulcerations associated with inflammation and edema, pathologically accompanied with signs of both rejection and viral infection. Though she was treated with bolus steroid for acute cellular rejection, a part of the ulceration did not improve, and the most distal part of the graft became stenotic. So she underwent partial resection of that part, and the symptoms improved. Partial resection of a graft stenosis part after a small bowel transplant can salvage a graft.

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  • Kiyotaka HOSODA, Yuichi MASUDA, Makoto KOYAMA, Yasunari OHNO, Atsuyosh ...
    2017 Volume 52 Issue 1 Pages 081-086
    Published: March 10, 2017
    Released on J-STAGE: April 04, 2017
    JOURNAL FREE ACCESS

    Liver cirrhosis resulting from the recurrence of hepatitis in patients with hepatitis C virus (HCV) is the major cause of graft loss after liver transplantation (LT). The effectiveness of treatment by direct-acting antiviral agents (DAAs) against HCV has been reported in LT patients. We report our experiences of anti-HCV therapy using DAAs in long-term HCV recipients. Five patients treated with DAAs were included in this study. Two patients were treated with pegylated-interferon (peg-IFN), ribavirin (RBV), and simeprevir (SMV), and three were with daclatasvir (DCV) and asunaprevir (ASV). All five had been previously treated with interferon (IFN) or peg-IFN with RBV after LT. Four of them discontinued antiviral therapy because of heart failure, retinal detachment, cellulitis, or diabetes mellitus. HCV reappearance was experienced after in the remaining patient who continued the therapy. In all patients, the levels of serum HCV-ribo nucleic acid were decreased to the under-detection level within 15 weeks; sustained virological response 24 weeks after treatment (SVR24) was then achieved. HCV could be eradicated with DAAs therapy even in long-term LT patients with failed IFN.

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