Human amniotic stem cells improve hepatic microvascular dysfunction and portal hypertension in cirrhotic rats

Background and Aims: Portal hypertension is the main consequence of cirrhosis, responsible for the complications defining clinical decompensation. The only cure for decompensated cirrhosis is liver transplantation, but it is a limited resource and opens the possibility of regenerative therapy. We investigated the potential of primary human amniotic membrane-derived mesenchymal stromal (hAMSCs) and epithelial (hAECs) stem cells for the treatment of portal hypertension and decompensated cirrhosis. Methods: In vitro: Primary liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) from cirrhotic rats (chronic CCl4 inhalation) were co-cultured with hAMSCs, hAECs or vehicle for 24 hours, and their RNA profile was analysed. In vivo: CCl4-cirrhotic rats received 4x106 hAMSCs, 4x106 hAECs, or vehicle (NaCl 0.9%) (intraperitoneal). At 2-weeks we analysed: a) portal pressure (PP) and hepatic microvascular function; b) LSECs and HSCs phenotype; c) hepatic fibrosis and inflammation. Results: In vitro experiments revealed sinusoidal cell phenotype amelioration when co-cultured with stem cells. Cirrhotic rats receiving stem cells, particularly hAMSCs, had significantly lower PP than vehicle-treated animals, together with improved liver microcirculatory function. This hemodynamic amelioration was associated with improvement in LSECs capillarization and HSCs de-activation, though hepatic collagen was not reduced. Rats that received amnion derived stem cells had markedly reduced hepatic inflammation and oxidative stress. Finally, liver function tests significantly improved in rats receiving hAMSCs. Conclusions: This preclinical study shows that infusion of human amniotic stem cells effectively decreases PP by ameliorating liver microcirculation, suggesting that it may represent a new treatment option for advanced cirrhosis with portal hypertension

Spanish Lung Cancer Biomarker Testing Registry (Lungpath): Descriptive Analysis Focus in ALK Traslocation Results

Background Oncogenic ALK gene rearrangements are found in approximately 4% of non-small cell lung cancer (NSCLC). Treatment options such as ALK tyrosine kinase inhibitors lead to improved progression free survival and overall survival. Thus, biomarker testing on pathology specimens is an essential requirement to properly treat lung cancer (LC) patients. LungPath is an on-line tool developed by the Spanish Society of Pathology (SEAP) with free and voluntary participation of differents Departments of Pathology to registry, monitor and trace biomarker results in clinical practice. After initial data reclutation step, first objective is to realize a descriptive analysis of LungPath focusing on ALK traslocation testing. Method Descriptive analysis of the LungPath registry. Biomarkers determinations of LC patients were collected from March 2018 to January 2019, from 38 Spanish Departments of Pathology. Result Based on this real clinical practice database, 19.332 biomarkers were tested over a total of 4.773 samples from LC patients. Small lung biopsies (60%), surgical resection specimen (16,3%) and cell block cytology (10,7%) were the mainly used samples in addition to fine needle aspiration cytology (5,1%), blood (2,5%) and other non lung biopsies (5,4%). NSCLC accounts for 95,1% of cases, principally adenocarcinoma (66%), squamous cell carcinoma (SCC) (19%), NOS (not otherwise specified, 6,1%), large cell neuroendocrine carcinoma (3,7%) and large cell carcinoma accounting for 0,3%. In non-squamous samples, ALK traslocation was one of the most frequently analyzed biomarker (80,1%), on the other hand, in SCC, ALK traslocation was shortly analyzed (53,1%), being PD-L1 expression the main biomarker realized (73,6%). From the adenocarcinoma samples were ALK was tested the positivity rate was 3,4%, whereas, 2,4% were not valit determinations due to several reasons. Used techniques plus further information has also been analyzed. Conclusion Development of central biomarker databases, such as Lungpath, provide an opportunity to registry clinical practice data and in the future could be an useful tool to monitor, correlate results between different centers and improve the available knowledge regarding biomarkers in LC. According the international guidelines, EGFR mutation and ALK traslocation should be tested in all advanced NSCLC overall in lung adenocarcinoma. ALK traslocation was one of the main biomarkers tested in our database with 3,4% traslocation rate, similar with the literature reports