Liver sinusoidal endothelial and biliary cell repopulation following irradiation and partial hepatectomy

AIM: To investigate whether irradiation (IR) and partial hepatectomy (PH) may prepare the host liver for nonparenchymal cell (NPC) transplantation.METHODS: Livers of dipeptidyl peptidase(DPP)-deficient rats were pre-conditioned with external beam IR (25 Gy) delivered to two-thirds of the right liver lobules followed by a one-third PH of the untreated lob-ule. DPP-positive liver cells (NPC preparations enriched for liver sinusoidal endothelial cells (LSECs) and hepatocytes) were transplanted via the spleen into the recipient livers. The extent and quality of donor cell engraftment and growth was studied over a long-term interval of 16 wk after transplantation.RESULTS: Host liver staining demonstrated 3 different repopulation types. Well def ined clusters of donor-derived hepatocytes with canalicular expression of DPP were detectable either adjacent to or in between large areas of donor cells (covering up to 90% of the section plane) co-expressing the endothelial marker platelet endothelial cell adhesion molecule. The third type consisted of formations of DPP-positive duct-like structures which co-localized with biliary epithelial CD49f.CONCLUSION: Liver IR and PH as a preconditioning stimulus enables multiple cell liver repopulation by donor hepatocytes, LSECs, and bile duct cells.

Stem cell differentiation and human liver disease

Human stem cells are scalable cell populations capable of cellular differentiation.This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells.Such an approach has the potential to improve our understanding of human biology and treating disease.In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases.In recent years,eff icient hepatic differentiation from human stem cells has been achieved by several research groups including our own.In this review we provide an overview of the f ield and discuss the future potential and limitations of stem cell technology.

Rapamycin increased development of CD4^+ CD25~h ighFoxp3^+ T cells of peripheral blood in liver transplant recipients

Objective To investigate the possible influence of immunosuppressive therapy,including sirolimus ( SRL) and calcineurin inhibitors ( CNI,tacrolimus) ,on level of Treg in liver allo - graft recipients. Methods Forty - seven liver transplant recipients with stable liver function were assessed for at least 2 years,and divided into

Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells

AIM： To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells （ADSC） and bone marrow-derived mesenchymal stem cells （BMSC） in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been described. Adipose tissue represents an accessible source of ADSC, with similar characteristics to BMSC. METHODS： BMSCs were obtained from patients undergoing total hip arthroplasty and ADSC from human adipose tissue obtained from lipectomy. Cells were grown in medium containing 15% human serum. Cultures were serum deprived for 2 d before cultivating under similar pro-hepatogenic conditions to those of liver development using a 2-step protocol with sequential addition of growth factors, cytokines and hormones. Hepatic differentiation was RT-PCR-assessed and liver-marker genes were immunohistochemically analysed.RESULTS： BMSC and ADSC exhibited a fibroblastic morphology that changed to a polygonal shape when cells differentiated. Expression of stem cell marker Thyl decreased in differentiated ADSC and BMSC. However, the expression of the hepatic markers, albumin and CYPs increased to a similar extent in differentiated BMSC and ADSC. Hepatic gene activation could be attributed to increased liver-enriched transcription factors （C/EBPβ and HNF4α）, as demonstrated by adenoviral expression vectors.CONCLUSION： Mesenchymal stem cells can be induced to hepatogenic transdifferentiation in vitro. ADSCs have a similar hepatogenic differentiation potential to BMSC, but a longer culture period and higher proliferation capacity. Therefore, adipose tissue may be an ideal source of large amounts of autologous stem cells, and may become an alternative for hepatocyte regeneration, liver cell transplantation or preclinical drug testing.

Chimera formation of platelet GPⅡb Bak a/b by intrauterine transplantation of fetal liver stem cells

Abstract:Objective To investigate whether artificial heterozygous chimeras of platelets can be established by intrauterine transplantation of fetal liver stem cells and evaluate its potential use for the treatment of Glanzmann thrombasthenia.Methods Platelet glycoprotein (GP) Ⅱb Bak a/b (or GPⅡb Ⅰle843Ser) was used as a genetic marker. A homozygous 16-week-old Bak a/a fetus (as donor) and a homozygous 16.5-week-old Bak b/b fetus (as recipient) were screened from 42 pregnant women hospitalized for abortion. PCR with allele specific primers and FOK Ⅰ digestion based on PCR products were used. Aborted donor fetal liver cell suspensions were prepared and intrauterine transplantation was carried out by infusion of 4?ml fetal liver cells (22×105) into the recipient umbilical vein under ultrasonic visualization.Results At gestation termination (abortion), 21 days after transplantation, chimera GPⅡb Bak a/b of the recipient were detected by FOK 1 digestion based on PCR from DNA and RT-PCR from platelet RNA. Conclusion Intrauterine transplantation of fetal liver cell may provide an effective way for curing GT or other inherited diseases.