Hepatocyte Transplantation

Mitry, Ragai R.; Hughes, Robin D.; Dhawan, Anil

doi:10.1016/s0973-6883(11)60129-1

Cited by 9 publications

(8 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical experience to date with hepatocyte or islet transplant to the liver demonstrate the failure to achieve long-term cellular allograft survival despite the use of conventional immunosuppression. Thus, in contrast to the immunotolerant theory of the liver microenvironment which would predict the need for minimal immunosuppression, the current studies highlight the need to develop more effective immunotherapeutic strategies to target both unique CD8-mediated immune responses primed in the liver and conventional alloimmune rejection pathways 13,17,18,71 .…”

Section: Discussionmentioning

confidence: 95%

“…Both the current experimental studies and clinical experience highlight that hepatocytes can be successfully transplanted either by intraportal or by intrasplenic injection 13,17–19 . However, despite reports that the liver immune environment may lead to poor CD8 + T cell activation and apoptosis contributing to tolerance induction 43 , we report here that allogeneic hepatocytes are highly immunogenic and are rejected rapidly, in a CD8-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, despite promising 1-year islet allograft survival rates in diabetic patients, the majority of recipients are not insulin free at 3 years posttransplant 15,16 . Similarly, allogeneic hepatocyte grafts transplanted into patients with metabolic disorders or liver failure exhibit significant but short-lived benefits ranging 3–26 months posttransplant 13,17–19 . This disparity, between whole liver transplantation and parenchymal cell transplants implanted into the liver, may be explained by a tightly regulated balance between immune reactivity and tolerance within the liver immune environment 10,20 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Unique CD8+ T Cell–Mediated Immune Responses Primed in the Liver

et al. 2016

View full text Add to dashboard Cite

Background The liver immune environment is tightly regulated to balance immune activation with immune tolerance. Understanding the dominant immune pathways initiated in the liver is important since the liver is a site for cell transplantation, such as for islet and hepatocyte transplantation. The purpose of this study is to examine the consequences of alloimmune stimulation when allogeneic cells are transplanted to the liver in comparison to a different immune locale, such as the kidney. Methods We investigated cellular and humoral immune responses when allogeneic hepatocytes are transplanted directly to the recipient liver by intraportal injection. A heterotopic kidney engraftment site was used for comparison to immune activation in the liver microenvironment. Results Transplantation of allogeneic hepatocytes delivered directly to the liver, via recipient portal circulation, stimulated long-term, high magnitude CD8+ T cell-mediated allocytotoxicity. CD8+ T cells initiated significant in vivo allocytotoxicity as well as rapid rejection of hepatocytes transplanted to the liver even in the absence of secondary lymph nodes or CD4+ T cells. In contrast, in the absence of recipient peripheral lymphoid tissue and CD4+ T cells, CD8-mediated in vivo allocytotoxicity was abrogated and rejection was delayed when hepatocellular allografts were transplanted to the kidney subcapsular site. Conclusions These results highlight the CD8-dominant proinflammatory immune responses unique to the liver microenvironment. Allogeneic cells transplanted directly to the liver do not enjoy immune privilege but rather require immunosuppression to prevent rejection by a robust and persistent CD8‐dependent allocytotoxicity primed in the liver.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Unique CD8+ T Cell–Mediated Immune Responses Primed in the Liver

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Since the donor hepatocytes are limited here, alternative cell sources are being investigated as hepatocytes generated by transdifferentiation or induced pluripotent stem cells (iPSCs) derived hepatocyte-like cells. 48 , 49 …”

Section: General Approaches To Pficmentioning

confidence: 99%

Progressive familial intrahepatic cholestasis: diagnosis, management, and treatment

Günaydın¹,

Çil²

2018

HMER

View full text Add to dashboard Cite

Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive cholestatic liver diseases which are subgrouped according to the genetic defect, clinical presentation, laboratory findings and liver histology. Progressive liver fibrosis, cirrhosis, and end stage liver disease (ESLD) may eventually develop. PFIC was first described in Amish descendants of Jacob Byler, therefore it was originally called Byler disease. But it can be seen anywhere on the globe. This review summarizes the main features of the subtypes of the disease and discusses the current available diagnosis, conservative and surgical therapeutic options.

show abstract

“…An ultimate treatment for severe liver failure is orthotropic liver transplantation (OLT), but the establishment of OLT as a common therapy is severely hampered by a worldwide shortage of donor livers [ 1 , 2 ]. As an alternative to OLT, a cell-based therapeutic using hepatocytes, known as hepatocyte transplantation, has been investigated and clinically conducted for liver failure and liver-based metabolic disorders [ 3 – 5 ]. In most cases of clinical hepatocyte transplantation, the hepatocytes which are freshly isolated or frozen dispersed are injected into the spleen or into the portal vein [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte Transplantation: Cell Sheet Technology for Liver Cell Transplantation

Tatsumi

Okano

2017

Curr Transpl Rep

View full text Add to dashboard Cite

Purpose of ReviewWe will review the recent developments of cell sheet technology as a feasible tissue engineering approach. Specifically, we will focus on the technological advancement for engineering functional liver tissue using cell sheet technology, and the associated therapeutic effect of cell sheets for liver diseases, highlighting hemophilia.Recent FindingsCell-based therapies using hepatocytes have recently been explored as a new therapeutic modality for patients with many forms of liver disease. We have developed a cell sheet technology, which allows cells to be harvested in a monolithic layer format. We have succeeded in fabricating functional liver tissues in mice by stacking the cell sheets composed of primary hepatocytes. As a curative measure for hemophilia, we have also succeeded in treating hemophilia mice by transplanting of cells sheets composed of genetically modified autologous cells.SummaryTissue engineering using cell sheet technology provides the opportunity to create new therapeutic options for patients with various types of liver diseases.

show abstract

Hepatocyte Transplantation

Cited by 9 publications

References 44 publications

Unique CD8+ T Cell–Mediated Immune Responses Primed in the Liver

Unique CD8+ T Cell–Mediated Immune Responses Primed in the Liver

Progressive familial intrahepatic cholestasis: diagnosis, management, and treatment

Hepatocyte Transplantation: Cell Sheet Technology for Liver Cell Transplantation

Contact Info

Product

Resources

About