• 대한이식학회지
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• 제28권3호
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• pp.160-164
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• 2014

Background: In solid organ transplantation patients, complications of cholelithiasis may run a fulminant course, resulting in high morbidity and mortality under immunosuppression and may even result in rejection. Here, we reviewed medical records of 66 patients in order to determine the outcome of management approach for asymptomatic gallstones in renal transplantation patients. Methods: We retrospectively reviewed clinical courses of 66 cases of renal transplantation performed between 2000 and 2012 at Kosin University Gospel Hospital. Results: Among 66 cases, eight had gallstones before transplantation. Three of these cases had undergone previous cholecystectomy for symptomatic gallstones, one had a simultaneous laparoscopic cholecystectomy and renal transplantation, and four were observed by regular abdominal ultrasonography. One patient was found to have cholangitis, and endoscopic retrograde biliary drainage was performed, resulting in alleviation of symptoms. Among 58 cases without preoperative gallstones, three developed gallstones after transplantation. One patient had cholecystitis, and the symptoms subsided after conservative treatment. Conclusions: For patients with asymptomatic gallstones who are awaiting renal transplantation, expectant management should be considered.

• IMMUNE NETWORK
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• 제4권1호
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• pp.1-6
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• 2004

Transplantation would be the only way to cure the end-stage organ failure involving heart, lung, liver, kidney and pancreas. The replacement of the parts of the body damaged to lose its function or lost to trauma must be a dream of human-being. Human history is replete with chimeras, from sphinxes to mermaids, making one wonder if the ancients might actually have dreamed of what now is called 'xenotransplantation'. In the 20th century, the transplantation of organs and tissues to cure disease has become a clinical reality. The development in the fields of surgical techniques, physiology and immunology attributed to the successful transplantation in human. In the center of the successful transplantation lies the progress in understanding the cellular and molecular biology of immune system which led to the development of immunosuppressive drugs and the invention of the concept of immunological tolerance. The mandatory side effects of immunosuppressive drugs including infection and cancer forced us to search alternative approaches along with the development of new immunosuppressive agents. Among the alternative approaches, the induction of a state of immunologic tolerance would be the most promising and the most generic applicability as a future therapy. Recent reports documenting long-term graft survival without immunosuppression suggest that tolerance-based therapies may become a clinical reality. Last year, we saw the epoch making success of overcoming hyperacute rejection in porcine to primate xenotransplantation which will lead porcine to human xenotransplantation to clinical reality. In this review, I dare to summarize the development of transplantation immunology from the perspective of history.

• BMB Reports
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• 제45권1호
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• pp.51-56
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• 2012

The purpose of this study was to determine the effects of duration and timing of glucocorticoid treatment on the expansion and differentiation of porcine neonatal pancreas cell clusters (NPCCs) into ${\beta}$-cells. After transplantation of NPCCs, the ductal cyst area and ${\beta}$-cell mass in the grafts both showed positive and negative correlations with duration of dexamethasone (Dx) treatment. Pdx-1 and HNF-3${\beta}$ gene expression was significantly downregulated following Dx treatment, whereas PGC-1${\alpha}$ expression increased. Pancreatic duct cell apoptosis significantly increased following Dx treatment, whereas proliferation did not change. Altogether, transdifferentiation of porcine NPCCs into ${\beta}$-cells was influenced by the duration of Dx treatment, which might have been due to the suppression of key pancreatic transcription factors. PGC-1${\alpha}$ plays an important role in the expansion and transdifferentiation of porcine NPCCs, and the initial 2 weeks following transplantation of porcine NPCCs is a critical period in determining the final ${\beta}$-cell mass in grafts.

• BMB Reports
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• 제54권7호
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• pp.356-367
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• 2021

Cell-based therapy is a promising approach in the field of regenerative medicine. As cells are formed into spheroids, their survival, functions, and engraftment in the transplanted site are significantly improved compared to single cell transplantation. To improve the therapeutic effect of cell spheroids even further, various biomaterials (e.g., nano- or microparticles, fibers, and hydrogels) have been developed for spheroid engineering. These biomaterials not only can control the overall spheroid formation (e.g., size, shape, aggregation speed, and degree of compaction), but also can regulate cell-to-cell and cell-to-matrix interactions in spheroids. Therefore, cell spheroids in synergy with biomaterials have recently emerged for cell-based regenerative therapy. Biomaterials-assisted spheroid engineering has been extensively studied for regeneration of bone or/and cartilage defects, critical limb ischemia, and myocardial infarction. Furthermore, it has been expanded to pancreas islets and hair follicle transplantation. This paper comprehensively reviews biomaterials-assisted spheroid engineering for regenerative therapy.

• BMB Reports
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• 제52권9호
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• pp.554-559
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• 2019

Despite reports suggesting that tissue-resident natural killer (trNK) cells cause ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has not been determined. This study hypothesized that the depletion of trNK cells may ameliorate renal fibrosis by affecting transglutaminase 2/syndecan-4 interactions. Aristolochic acid nephropathy (AAN) was induced in C57BL/6 mice as an experimental model of kidney fibrosis. The mice were treated with anti-asialo GM1 (ASGM1) or anti-NK1.1 antibodies to deplete NK cells. Although both ASGM1 and NK1.1 antibodies suppressed renal $NKp46^+DX5^+$ NK cells, renal $NKp46^+DX5^-$ cells were resistant to suppression by ASGM1 or NK1.1 antibodies during the development of tubulointerstitial fibrosis in the AAN-induced mouse model. Western blot analysis showed that both antibodies increased the expression of fibronectin, transglutaminase 2, and syndecan-4. These findings indicate that trNK cells played an exacerbating role in tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in the AAN-induced mouse model.

• Applied Microscopy
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• 제37권4호
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• pp.249-258
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• 2007

이자섬은 이자를 구성하는 외분비조직에 둘러싸여 존재하는 내분비세포의 집단으로, 이자섬에서 분비되는 인슐린은 $\beta$세포에서 분비되는 호르몬이며, 세포질의 리보좀에서 합성되고 골지체를 경유하여 세포질로 방출되는 기작을 가지고 있다. 충분한 양의 이자섬 이식은 인슐린 의존형 당뇨병인 제1형 당뇨병에서 정상혈당을 회복시키고, 당뇨 합병증을 방지할 수 있는 치료방법으로 사용되고 있다. 하지만 당뇨병 환자에게 이식을 위한 이자섬의 양에 비해 공여자로부터 증여된 이자섬의 양은 제한적이다. 이러한 문제점은 이자섬의 증식으로 연구되고 있으나, 배양된 이자섬이 정상 조직내의 이자섬과 형태적 기능적으로 동일한 것인지에 관한 연구는 미비하였다. 따라서 본 연구에서는 분리된 이자섬과 배양된 이자섬을 구성하는 세포들의 내부구조의 변화를 주사전자현미경, 투과전자현미경을 이용하여 세포의 미세구조를 확인하고, 인슐린 항체를 이용한 $\beta$세포 내의 인슐린 분포양상을 확인하여 다음과 같은 결과를 얻었다. 분리된 이자섬의 $\beta$세포는 일반적인 핵 미토콘드리아, 세포질세망 그리고 인슐린 과립이 분포하고, 배양된 이자섬 $\beta$세포의 경우 분리된 이자섬에 비하여 일반적인 핵의 모습과 부피가 증가한 세포질과 미토콘드리아, 세포질세망 그리고 골지체의 발달이 이루어지는 것으로 관찰되었다. 인슐린 과립의 경우 분리된 이자섬에 비해 감소하며, 세포막 주위에 분포하는 것으로 관찰되었다. 배양된 이자섬에서 관찰되는 인슐린 과립 분포의 변화, 세포질세망의 증가, 골지체의 발달은 배양된 이자섬 $\beta$세포의 인슐린 생성 분비 기능의 향상과 부피의 증가가 이루어지기 위한 세포 내부의 형태적 변화가 이루어지는 것으로 추측된다.

• 한국임상약학회지
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• 제9권2호
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• pp.81-87
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• 1999

췌장이식의 성공률은 지난 10년 동안 상당히 상승되었다. International Pancreas Transplant Registry에 따르면 1995년 이래 미국에서만 매년 1,000건 이상의 췌장이식이 실시되고 있다. 장기이식후 나타나는 급성 거부반응은 이식 후 6개월 이내에 가장 높은 빈도수로 나타난다. 췌장이식환자에서는 신장을 이식한 것보다 두배나 높은 거부반응을 나타나며 이로 인한 입원율의 증가 항림프제(antilyinphocyte) 사용과 감염의 증가로 이환율이 높다. 더구나 Cyclosporine (CsA)을 기초로 한 면역억제제요법의 사용은 높은 급성 거부반응률(acute graft rejection)을 초래하여 이식한 장기의 조직손실이 문제가 되고 있다. 새로운 면역억제제인 Tacrolimus (FK506)의 사용은 이식환자에서의 거부반응을 감소시켜 생존율을 증가시키는 것으로 알려져 있다. Tacrolimus는 neutral macrolide로 cyclic peptide인 CsA과는 화학 구조는 매우 다르나 비슷한 면역억제 효과를 보인다. 하지만 Tacrolimus의 사용시 신경독성, 신독성, 특히 고혈당증의 발생률이 높아 일부 이식센터에서는 장기 이식 후에 사용하기를 꺼리기도 한다. 하지만 여러 연구논문에서 간과 신장 이식 후 급성 거부반응 예방에 Tacrolimus는 CsA에 비해 이점이 있는 결과를 발표하였다. 결과적으로, 현재 췌장이식 후 Tacrolimus를 기초로 한 면역억제의 효과에 대한 연구가 활발히 진행중이다. 따라서 본 연구에서는 1994-1996년 사이에 Tacrolimus 또는 CsA를 기초로 한 면역억제요법을 투여 받은 췌장이식환자 101명을 후향적으로 조사하여 Tacrolimus (n=54)와 CsA(n=57)의 급성 거부반응 예방 효과와 신부전 발생률을 비교하였다. 모든 환자는 항림프구 약물, Azathioprine, Prednisone을 이식 후 면역억제제로 투여 받았다 기준선으로부터 $20\%$ 이상의 혈청 creatinine의 상승이 있는 환자에서는 급성 신부전으로 정의하였고 신장생검법으로 거부반응을 진단하였다 Matched-pair analysis에 따르면 췌장이식환자의 6개월 생존율은 CsA군에서 $97\%$, Tacrolimus군에서 $96\%$로 별다른 차이가 없었으며 (p=0.57), 6개월간의 이식한 췌장의 보존율은 CsA군에서는 $88\%, Tacrolimus에서 $91\%$. 유의한 차이는 없었다(p=0.29). 췌장이식 후 6개월 동안 Tacrolimus의 사용은 생검으로 증명되는(biopsy-proven) 급성 거부반응의 발생빈도는 CsA보다 유의하게 낮았을 뿐만 아니라 (p<0.05) 거부반응 증상의 심각도 또한 감소시켰다 (p=0.03). 급성거부반응 발생빈도의 감소로 Tacrolimus군에서 antilymphocyte 치료가 유의하게 줄어들었다(p=0.01). CsA군에서 Tacrolimus보다 신부전의 발생률이 높았으나 통계학적 차이는 없었다. 췌장이식후의 최적의 면역억제요법의 결정하기 위해서는 향후 Tacrolimus와 CsA을 비교하는 전향적 무작위 연구가 필요하다.

• 한국수정란이식학회지
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• 제30권3호
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• pp.249-255
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• 2015

Diabetes mellitus, the most common metabolic disorder, is divided into two types: type 1 and type 2. The essential treatment of type 1 diabetes, caused by immune-mediated destruction of ${\beta}-cells$, is transplantation of the pancreas; however, this treatment is limited by issues such as the lack of donors for islet transplantation and immune rejection. As an alternative approach, stem cell therapy has been used as a new tool. The present study revealed that bone marrowderived mesenchymal stromal cells (BM-MSCs) could be transdifferentiated into pancreatic cells by the insertion of a key gene for embryonic development of the pancreas, the pancreatic and duodenal homeobox factor 1 (PDX1). To avoid immune rejection associated with xenotransplantation and to develop a new cell-based treatment, BM-MSCs from ${\alpha}$-1,3-galactosyltransferase knockout (GalT KO) pigs were used as the source of the cells. Transfection of the EGFP-hPDX1 gene into GalT KO pig-derived BM-MSCs was performed by electroporation. Cells were evaluated for hPDX1 expression by immunofluorescence and RT-PCR. Transdifferentiation into pancreatic cells was confirmed by morphological transformation, immunofluorescence, and endogenous pPDX1 gene expression. At 3~4 weeks after transduction, cell morphology changed from spindle-like shape to round shape, similar to that observed in cuboidal epithelium expressing EGFP. Results of RT-PCR confirmed the expression of both exogenous hPDX1 and endogenous pPDX1. Therefore, GalT KO pig-derived BM-MSCs transdifferentiated into pancreatic cells by transfection of hPDX1. The present results are indicative of the therapeutic potential of PDX1-expressing GalT KO pig-derived BM-MSCs in ${\beta}-cell$ replacement. This potential needs to be explored further by using in vivo studies to confirm these findings.

• Anatomy and Cell Biology
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• 제51권4호
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• pp.232-235
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• 2018

Portal vein provides about three-fourths of liver's blood supply. Portal vein is formed behind the neck of pancreas, at the level of the second lumbar vertebra and formed from the convergence of superior mesenteric and splenic veins. The purpose of this study is to review the normal distribution and variation, morphometry of portal vein and its branches for their implication in liver surgery and preoperative portal vein embolization. It is also helpful for radiologists while performing radiological procedures. A total of fresh 40 livers with intact splenic and superior mesenteric vein were collected from the mortuary of Forensic Department, JSS Medical College and Mysuru Medical College. The silicone gel was injected into the portal vein and different segments were identified and portal vein variants were noted. The morphometry of portal vein was measured by using digital sliding calipers. The different types of portal vein segmental variants were observed. The present study showed predominant type I in 90% cases, type II 7.5% cases, and type III 2.5% cases. Mean and standard deviation (SD) of length of right portal vein among males and females were $2.096{\pm}0.602cm$ and $1.706{\pm}0.297cm$, respectively. Mean and SD of length of left portal vein among males and females were $3.450{\pm}0.661cm$ and $3.075{\pm}0.632cm$, respectively. The difference in the Mean among the males and females with respect to length of right portal vein and left portal vein was found to be statistically significant (P=0.010). Prior knowledge of variations regarding the formation, termination and tributaries of portal vein are very helpful and important for surgeons to perform liver surgeries like liver transplantation, segmentectomy and for Interventional Radiologists.

• 한국수정란이식학회지
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• 제32권3호
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• pp.73-79
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• 2017

Transplantation is considered to be a very useful approach to improve human welfare and to prolong life-span. Heterologous organ transplantation using pig organs which are similar to human beings and easy to make mass-production has known as one of the alternatives. To ensure potential usage of the pig organ for transplantation application, it is essentially required to generate transgenic pig modifying immuno-related genes. Previously, we reported production of heterozygous ${\alpha}1,3$-galactosyltransferase (GalT) knock-out and human membrane cofactor protein (MCP) expressing pig ($GalT^{-MCP/+}$), which is enforced for suppression of hyperacute and acute immunological rejection. In this study, we reported generation of homozygous pig ($GalT^{-MCP/-MCP}$) by crossbreeding $GalT^{-MCP/+}$ pigs. Two female founders gave birth to six of $GalT^{-MCP/-MCP}$, and seven $GalT^{-MCP/+}$ pigs. We performed quantitative real-time PCR, western blot, and flow cytometry analyses to confirm GalT and MCP expression. We showed that fibroblasts of the $GalT^{-MCP/-MCP}$ pig do not express GalT and its product Gal antigen, while efficiently express MCP. We also showed no expression of GalT, otherwise expression of MCP at heart, kidney, liver and pancreas of transgenic pig. Taken together, we suggest that the $GalT^{-MCP/-MCP}$ pig is a useful candidate to apply xenotransplantation study.