PURPOSE: Whole liver transplantation, an effective therapy for many inherited and acquired hepatic disorders, has limitations including donor shortage and fatal surgical complications. Hepatocyte transplantation, which is simpler and less expensive than whole liver transplantation, allows the use of living related donors, permits the use of a single donor organ for multiple recipients, and makes possible the cryopreservation of hepatocytes for future use. However, choosing a proper scaffold for hepatocyte transplantation hampers wide use of hepatocyte transplantation. We performed hepatocyte transplantation using fibrin gel, as a cell transplantation scaffold and evaluated their effectiveness. METHODS: Female, five week old FVB mice, were prepared for donors, and two male, five week old nude mice, were used as recipients. Liver cells were isolated from FVB donors. The cell viability exceeded 95% as assessed by the trypan blue exclusion method. For three nude mice, 5x10(6) cells resuspended in 500microliter of fibrinogen were mixed with 500microliter thrombin, and were injected into the peritoneal cavity of each mouse. One nude mouse was transplanted with 5x10(6) cells resuspended in 500 microliter medium, which served as a negative control. Specimens were retrieved at one week, and histological and immunohistochemical analyses wereperformed. RESULTS: In the negative control, all transplanted hepatocytes disappeared at one week. In mice transplanted both fibrin gel and hepatocytes, conglomerates containing hepatocytes were observed on the intestinal mesentery. The hepatocytes were identified by H & E staining and immunohistochemistry using anti-hepatocyte antibody. Functional activity was evaluated with PAS staining. CONCLUSION: In this preliminary study, stable hepatocyte engraftment was achieved in hepatocyte transplantation with fibrin gel, but not in hepatocyte transplantation without scaffold. More studies on comparison between fibrin gel and injectable scaffolds would be necessary. Improvement on both initial vascularization and proliferation of transplanted hepatocytes is a target of our future work.
Animals ; Cell Survival ; Cell Transplantation ; Cryopreservation ; Female ; Fibrin* ; Fibrinogen ; Hepatocytes* ; Humans ; Immunohistochemistry ; Liver ; Liver Transplantation ; Male ; Mesentery ; Mice ; Mice, Nude ; Peritoneal Cavity ; Thrombin ; Tissue Donors ; Transplants ; Trypan Blue

PURPOSE: Dialysis and renal transplantation, the current therapies for end-stage renal disease (ESRD), have limitations including severe complications, donor organ shortage, and allograft failure. The present study investigated the possibility of using a tissue engineering technique for renal reconstruction as a new method to replace the current suboptimal treatments for ESRD. We reconstituted renal units in vivo by transplanting isolated renal segments on three-dimensional, biodegradable polymer scaffolds. METHODS: Renal segments were freshly isolated from Sprague-Dawley rat kidneys and seeded onto porous mesh matrices fabricated from polyglycolic acid, a biodegradable synthetic polymer. The renal segment-seeded scaffolds were implanted into subcutaneous spaces of athymic mice for two and four weeks. Retrieved specimens were examined by histological analyses. RESULTS: The tubular structures with hollow centers and vascular tufts of glomerulus-like structures were identified by histological analyses of the 2 and 4 week specimens. In contrast, no renal-like structures were observed from unseeded polymer implants (negative controls). CONCLUSION: These results suggest a possibility of reconstituting the renal structures by transplanting renal segments on polymer scaffolds and could be applid for partial or full replacement of kidney function in the treatment of ESRD.
Allografts ; Animals ; Dialysis ; Humans ; Kidney ; Kidney Failure, Chronic ; Kidney Transplantation ; Mice ; Mice, Nude ; Polyglycolic Acid ; Polymers* ; Rats ; Rats, Sprague-Dawley ; Tissue Donors ; Tissue Engineering

PURPOSE: The host immune responses to skin xenografts are known to be much stronger than those to allografts. The possible reasons for that, however, are unclear. We hypothesized that chemokines trafficking leukocytes may be involved in stronger xenograft rejection process as compared to allograft rejection. METHODS: Thus, we evaluated the profiles of chemokine expression and cellular infiltration in the skin xenografts and compared to those in fully allogeneic skingrafts. RESULTS: At day 5, post-transplantation the heavier cellular infiltration of CD4+, CD8+ T cells and neutrophils into xenografts was found as compared to allografts. Similarly, more CD8+ T, CD11b+ and MOMA-2+ cells were found to infiltrate into xenografts than allografts at day 7. The xenograft showed earlier and stronger mRNA expression of chemokines such as MCP-1, IP-10 and MIG. In the late phase of xenograft rejection, strong expression of RANTES and MIP-1a was noted. In xenografts, the time of expression of IP-10 and MIG was correlated with the time of infiltration of CD4+, CD8+ cells and neutrophils whereas, the expression patterns of RANTES and MIP-1a were similar to the infiltration patterns of CD11b+ and MOMA-2+ cells. CONCLUSION: These results suggest that the prompt xenograft cellular rejection as compared to the allograft rejection may be related to the rapid induction of pro-inflammatory chemokines such as MCP-1, IP-10 and MIG in the early phase and resultant significant infiltration of CD4+ and CD8+ T cells and neutrophils.
Allografts ; Chemokine CCL5 ; Chemokines ; Heterografts* ; Leukocytes ; Neutrophils ; RNA, Messenger ; Skin* ; T-Lymphocytes ; Transplantation, Heterologous

PURPOSE: Vascular smooth muscle cell (VSMC) proliferation and extracellular matrix protein accumulation play important roles in chronic allograft vasculopathy. Mycophenolic acid (MPA) or rapamycin (RPM) was reported to inhibit VSMC proliferation in vitro and in vivo. However, effects of MPA or RPM on collagen synthesis of VSMCs, and the combined effects of MPA and RPM treatment on VSMC proliferation are not yet reported. METHODS: VSMCs isolated from the aorta of Sprague-Dawley rats were cultured with EMEM supplemented with 10% fetal bovine serum and insulin/ transferrin. Growth arrested and synchronized cells were pretreated with test drugs (alone or combination of various concentrations of MPA and RPM) 1 hour before the addition of 10 ng/ml PDGF. Cell proliferation was assessed by [H3]- thymidine incorporation, and collagen synthesis by [H3]- proline incorporation. RESULTS: PDGF increased cell proliferation and collagen synthesis by 3.4- and 2.1-fold, respectively, compared to control. MPA at above 100 nM or RPM at above 1 nM effectively inhibited PDGF-induced cell proliferation and collagen synthesis. The IC50 of MPA or RPM against PDGF-stimulated cell proliferation was between 100 nM and 1 micrometer or between 1 nM and 10 nM, respectively. The combination of MPA and RPM showed additive effects on PDGF-induced VSMC proliferation in a multiple regression analysis (R2=0.508, P<0.05). CONCLUSION: The present study demonstrated that MPA or RPM significantly inhibited PDGF-induced VSMC proliferation. These independent phenomena were well maintained as suggested by additive effects after combination treatment. PDGF-induced collagen synthesis was also effectively suppressed by the treatment of MPA or RPM.
Allografts ; Animals ; Aorta ; Cell Proliferation ; Collagen* ; Extracellular Matrix ; Inhibitory Concentration 50 ; Muscle, Smooth, Vascular* ; Mycophenolic Acid* ; Proline ; Rats* ; Rats, Sprague-Dawley ; Sirolimus* ; Thymidine ; Transferrin

ABO-incompatible kidney transplantations have been performed successfully in Korea without splenectomy using plasmapheresis, anti-CD20 monoclonal antibody infusions and other immunosuppressants. However, there is no report of a case of ABO-incompatible kidney transplantation in a Jehovah's Witness. Hence, we report our experience of successful ABO-incompatible kidney transplantation without blood products in a Jehovah's Witness. The recipient was treated with six sessions of plasmapheresis and he received intravenous rituximab before transplantation. Immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil and steroid. The replacement fluid for plasmapheresis was 5%% albumin solution instead of fresh frozen plasma. We measured the clotting factors before and after plasmapheresis and used cryoprecipitate to prevent bleeding.
Antibodies, Monoclonal, Murine-Derived ; Hemorrhage ; Humans ; Immunosuppressive Agents ; Kidney ; Kidney Transplantation ; Korea ; Living Donors ; Mycophenolic Acid ; Plasma ; Plasmapheresis ; Rituximab ; Splenectomy ; Tacrolimus ; Transplants ; Wit and Humor as Topic

BACKGROUND: At the initiation of immunologic response, platelets rapidly release chemical mediators which may induce rejection of transplanted organ. The purpose of this study was to investigate the effect of antiplatelet agents in murine cardiac and skin transplantation models. METHODS: In the minor major histocompatibility (MHC) mismatch model, BALB/c (H2d) mice underwent heart transplantation from B10.D2 (H2d) mice. In the major MHC mismatch model, CBA (H2k) mice were used as the recipients and C57BL/10 (H2b) mice as donors. The recipients were divided into four groups and each group was treated with distilled water (DW), sarpogrelate, cilostazol, or clopidogrel respectively. For skin transplantation, the recipients in the minor MHC mismatch model were divided into four groups similar to those in cardiac transplantation. The recipients in the major MHC mismatch model were divided into DW-treated and sarpogrelate-treated groups. All treatments were done by the per oral route of administration. RESULTS: For graft survival in the minor MHC mismatch model of cardiac transplantation, sarpogrelate-treated group showed increased median survival time (MST) compared to the other groups (DW-treated group 17.5 days, sarpogrelate-treated group 88 days, cilostazol-treated group 13 days, clopidogrel-treated group 23 days). Similar results were observed in the major MHC mismatch model. In the major MHC mismatch model, the expression of adhesion molecules (L-selectin, intercellular adhesion molecule-1 [ICAM-1], Mac-1, lymphocyte function associated antigen-1 [LFA-1]) was significantly higher in DW-treated group compared to sarpogrelate-treated group (P<0.05) In the minor MHC mismatch model, MST in the antiplatelet-treated skin graft group was not remarkably prolonged compared to DW-treated group. In the major MHC mismatch model, sarpogrelate-treated group showed prolonged survival compared to DW-treated group (MST 25 vs. 19 days, P<0.05). There was no statistically significant difference in the proportion of activated T cells and regulatory T cells. CONCLUSIONS: The tendency for a better survival of grafts was observed in the sarpogrelate-treated skin and heart transplant group compared to DW-treated group. However, further mechanistic study is necessary to these results.
Animals ; Blood Platelets ; Graft Survival ; Heart ; Heart Transplantation ; Histocompatibility ; Humans ; Intercellular Adhesion Molecule-1 ; Lymphocytes ; Mice ; Platelet Aggregation Inhibitors ; Rejection (Psychology) ; Skin ; Skin Transplantation ; Succinates ; T-Lymphocytes ; Tetrazoles ; Ticlopidine ; Tissue Donors ; Transplants ; Water

BACKGROUND: The incidence of acute rejection has decreased with the introduction of new immunosuppressive agents. However, several studies have shown that allograft survival has not clearly improved over the past few decades. METHODS: We reviewed patients who underwent kidney transplantation between 1982 and 2007. We compared the causes of graft loss for three decades: 1982~1990 (period I),1991~2000 (period II), and 2001~2007 (period III), with the clinical characteristics of patients with functioning grafts and patients who lost their allografts. RESULTS: There were 785 recipients with a mean age of 36.1 years, and 65.2% were male. Graft loss occurred in 329 patients (41.9%), and the most common cause of graft loss was chronic allograft nephropathy (CAN, 52.0%), followed by patient death (17.6%), post-transplant glomerulonephritis (12.8%), and non compliance (7.9%). During the three time periods, 129, 172, and 28 patients lost their grafts, respectively. Five-year graft survival was 61.5%, 78.4%, and 90.8%, respectively, and increased significantly (P<0.000). CAN, as a cause of graft loss, fell from 65.1% (period I) to 32.1% (period III, P<0.000), but patient death increased from 12.4% to 32.1% (P=0.034). A multivariate analysis revealed that significant risk factors for graft loss included an older donor, transplantation at period I, and dual immunosuppression. Use of tacrolimus and mycophenolate mofetil was associated with a significantly reduced risk of graft loss. CONCLUSIONS: Graft survival has increased over the last three decades whereas the proportion of CAN, the most common cause of graft loss, has decreased. Attention to the main causes of graft loss, CAN, and patient death will offer potential improvement in graft survival.
Compliance ; Glomerulonephritis ; Graft Rejection ; Graft Survival ; Humans ; Immunosuppression ; Immunosuppressive Agents ; Incidence ; Kidney ; Kidney Transplantation ; Male ; Multivariate Analysis ; Mycophenolic Acid ; Rejection (Psychology) ; Risk Factors ; Tacrolimus ; Time Factors ; Tissue Donors ; Transplantation, Homologous ; Transplants ; Treatment Outcome

Acute liver failure is a rapidly progressive disease of the liver associated with high morbidity and mortality without liver transplantation. Although good survival after transplantation can be achieved, due to the disparity between patients awaiting transplantation and available organs, many patients die due to progression of the disease while waiting for a liver graft. To reduce the high morbidity and mortality associated with acute liver failure, attempts have been made during the last several decades to develop a temporary liver support system, such as artificial and bioartificial livers. The artificial liver is a non-biological device mainly aimed at the removal of accumulated toxins during liver failure, and the bioartificial liver is a biological device that has bioreactors containing living hepatocytes which provide both biotransformation and synthetic liver functions. There are currently 3 artificial livers available in the market that have been actively used in the clinical field, and 11 bioartificial livers that have been developed and have undergone clinical trials. In this article, we will discuss about the 3 artificial liver devices and 5 bioartificial liver systems that are the most advanced and have been widely evaluated clinically. Also, the characteristics and the preclinical data of the first bioartificial liver system developed in Korea that is currently under clinical investigation, will be discussed.
Alginates ; Bioreactors ; Biotransformation ; Glucuronic Acid ; Hepatocytes ; Hexuronic Acids ; Humans ; Korea ; Liver ; Liver Failure ; Liver Failure, Acute ; Liver Transplantation ; Liver, Artificial ; Transplants

New-onset diabetes after transplantation (NODAT) is a common complication of solid-organ transplantation. As long-term posttransplant survival continues to improve, increasing attention has been placed on NODAT. Because NODAT is a potent predictor of graft failure and cardiovascular mortality in the transplant population, early detection and management of NODAT are important issues. The risk factors for NODAT in transplant recipients include older age, obesity, family history, hepatitis C virus infection, and immunosuppressive agents, such as corticosteroids and calcineurin inhibitors. Management of NODAT must be considered at the pretransplantation stage to screen high risk patients and prevent NODAT. Although NODAT management is similar to type 2 diabetes management in the general population, there are some specific considerations in NODAT management, including the immunosuppressive agent. Further studies are needed to suggest optimal management guidelines for NODAT.
Adrenal Cortex Hormones ; Calcineurin ; Diabetes Mellitus ; Hepacivirus ; Humans ; Immunosuppressive Agents ; Obesity ; Organ Transplantation ; Postoperative Complications ; Risk Factors ; Transplants ; Treatment Outcome

Since the first deceased donor kidney transplantation in 1979, continuous efforts have been made to increase deceased organ donation in Korea. However, a critical shortage of human organs for transplant is still a serious problem and is partly caused by the absence of a system to actively identify and properly manage deceased donors in Korea. Considering this, Korea needs to create a new national system for deceased donor identification, management, and organ procurement. There are three kinds of organ procurement systems in the world: The "Spanish model", the "United States model", and the "other European model". We reviewed each system and suggested the optimal organ procurement system for Korea. We also proposed requirements for operating an organ procurement organization and increasing deceased organ donation. Further improvements in the organ procurement system will contribute to improve the current organ shortage.
Brain Death ; Humans ; Kidney Transplantation ; Korea ; Spain ; Tissue and Organ Procurement ; Tissue Donors ; Transplants ; United States