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 under-going total hip arthroplasty and ADSC from human adi-pose 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 develop-ment using a 2-step protocol with sequential addition of growth factors, cytokines and hormones. Hepatic differ-entiation was RT-PCR-assessed and liver-marker genes were immunohistochemically analysed. RESULTS: BMSC and ADSC exhibited a fibroblastic mor-phology that changed to a polygonal shape when cells differentiated. Expression of stem cell marker Thy1 de-creased 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 in-creased liver-enriched transcription factors (C/EBPβ and HNF4α), as demonstrated by adenoviral expression vec-tors.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 ca-pacity. 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.

Hepatitis B transmission by cell and tissue allografts:How safe is safe enough?

More than 2 million human tissue transplants(bone,tendon,cartilage,skin,cornea,amniotic membrane,stem cells,heart valve,blood vessel,etc.),are performed worldwide every year.Cells and tissues are shared between countries which have different regulations and laboratory equipment and represent a risk of hepatitis B virus(HBV)transmission that has become a global safety concern.While the risk of transfusiontransmitted HBV infection from blood donations has been estimated,the rate of HBV transmission from donors to recipients of allografts is unknown and varies between different tissues.There are various important ways of reducing the transmission risk,but donor screening and donor testing are still the main factors for preventing HBV transmission.HBV detection is included in the routine screening tests for cell and tissue donors.The standard test for preventing transplant-transmitted hepatitis B is the hepatitis B surface antigen.The implementation of methods involving nucleic acid amplification and the new generation of reactives to detect viral antibodies or antigens with an immunoassay,has increased the sensitivity and the specificity of the screening tests.The objective of our research was to review the literature and critically analyse the different steps for avoiding HBV transmission in cell and tissue donors,focusing on the screening tests performed.

Risk assessment of hepatitis E transmission through tissue allografts

Hepatitis E virus(HEV)is a small non-enveloped single stranded RNA virus whose genotypes 3 and 4 have been associated with zoonotic transmission in industrialized countries.HEV infection is considered the main cause of acute hepatitis worldwide.In some cases,transfusion of blood components or organ transplantation have been reported as the source of infection.We have conducted a literature review on the risk of transmission through cell and tissue allografts.Although no case was found,measures to control this risk should be taken when donor profile(based upon geographical and behavioural data)recommended it.Issues to be considered in donor screening and tissue processing to assess and to reduce the risk of HEV transmission are approached.