Induced pluripotent stem cells (iPSCs) with potential for therapeutic applications can be derived from somatic cells via ectopic expression of a set of limited and defined transcription factors. However, due to risks of random integration of the reprogramming transgenes into the host genome, the low efficiency of the process, and the potential risk of virally induced tumorigenicity, alternative methods have been developed to generate pluripotent cells using nonintegrating systems, albeit with limited success. Here, we show that c-KIT+ human first-trimester amniotic fluid stem cells (AFSCs) can be fully reprogrammed to pluripotency without ectopic factors, by culture on Matrigel in human embryonic stem cell (hESC) medium supplemented with the histone deacetylase inhibitor (HDACi) valproic acid (VPA). The cells share 82% transcriptome identity with hESCs and are capable of forming embryoid bodies (EBs) in vitro and teratomas in vivo. After long-term expansion, they maintain genetic stability, protein level expression of key pluripotency factors, high cell-division kinetics, telomerase activity, repression of X-inactivation, and capacity to differentiate into lineages of the three germ layers, such as definitive endoderm, hepatocytes, bone, fat, cartilage, neurons, and oligodendrocytes. We conclude that AFSC can be utilized for cell banking of patient-specific pluripotent cells for potential applications in allogeneic cellular replacement therapies, pharmaceutical screening, and disease modeling.
Introduction Patients with end stage liver disease (ESLD) and/or hepato-cellular carcinoma (HCC) may be considered unsuitable for liver transplantation (LT) due to disease severity at presentation or de-listed due to disease progression. These patients have complex medical needs and a limited life expectancy and would be expected to benefit from access to palliative care services. Methods We performed a retrospective audit of patients assessed for LT between 2010-12 at the Royal Free Hospital. We studied patients who were either not listed at the time of assessment, or listed and subsequently de-listed prior to LT. Sources used included transplant meeting records, hospital notes, local death records and palliative care database. Results 106 patients were identified. Median age was 58 years (IQR 51-72) and 67% were male. The median MELD score at the time of assessment was 13 (IQR 11-18.75) with a UKELD score of 52 (IQR 49-57). Aetiology of liver disease was divided into Alcohol related Liver Disease (39), Viral (32), Autoimmune (19), Metabolic (8), Cryptogenic cirrhosis (3), other (5). Reasons for not listing included poor clinical state/co-morbidities (48), tumour outside transplant criteria (25), psychosocial/ compliance issues (18) and currently too well for LT (15). Excluding patients who were 'Too Well' for LT, Kaplan-Meier Survival analysis calculated the median survival following delisting as 219 days (IQR 28-540). Specifically for those delisted for 'poor clinical state' median survival was 29 days. Overall, 17 (19%) patients were referred to palliative care a median 4 days before death (IQR 2.5-47.5). Conclusion Those patients who are unfit for LT due to poor clinical state should be referred immediately for palliative care due to limited survival. Patients with HCC outside criteria have a significantly longer survival but still appear to have limited access to palliative care. Liver Transplant programs should have access to dedicated liver palliative care services.
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obtained, ease of diagnosis and the duration of tissue sampling and pathological reporting. Results 108 participants were recruited, 57 male; mean age 66.9 ± 10.9. 85.2% had a final diagnosis of malignancy. Median lesion size (IQR) was 25 mm (19-34.5). 62 (57.4%) of lesions were in the head of pancreas. Tissue results from the FNB needle were significantly more accurate than FNA (84.2% vs 75%, p=0.041) in discriminating malignant from benign masses. A greater proportion of FNB samples had abundant diagnostic material (59.2% vs 44.4%, p=0.017) and a straight forward diagnosis (68.9% vs 51.9%, p=0.03). Biopsy sampling time median (IQR) 685s (565-832) vs 752s (651-835), p=0.0006) and pathology reporting times (191s (134-258) vs 332s (260-358), p< 0.0001) were significantly shorter with FNB compared to FNA. Conclusion The diagnostic performance of the SharkCore™ FNB needle was significantly better than that of a standard FNA needle in the diagnosis of solid pancreatic masses and was associated with better sample quality, ease of reporting and shorter sampling and pathological reporting times.
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