scholarly journals Umbilical Cord Blood-Derived Mesenchymal Stem Cells Transplantation Decreases Incidence of Liver Cancer in End-Stage Liver Disease Patients: A Retrospective Analysis Over 5 Years

2021 ◽  
Author(s):  
Le Luo ◽  
Cun-You Lai ◽  
Tian-Hang Feng ◽  
Yu-Tong Yao ◽  
Hua Xue ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Liver Cancer ◽  
Umbilical Cord Blood ◽  
End Stage Liver Disease ◽  
Liver Cancers ◽  
End Stage

Abstract Background: End-stage liver disease (ESLD) is the final stage of a liver disease, which is characterized by liver cirrhosis. ESLD largely increases possibility of liver cancers in the world. The stem cell transplantation has become an emerging therapy to treat various liver diseases including ESLD, while whether it causes liver cancer remains unclear. The study aims to analysis the long-term therapeutic effect of umbilical cord blood-derived mesenchymal stem cells (UC-MSCs) transplantation in ESLD patients. Patients and Methods: 50 ELSD patients of non-UC-MSCs transplantation and 45 ELSD patients of UC-MSCs transplantation were retrospectively analyzed. The clinical outcomes in clinical and biochemical data, complications, and quality of life were recorded at 3, 6, 12, 36, and 60 months. Results: It was found that the incidence of liver cancer was much lower in ESLD patients with UC-MSCs transplantation than in ESLD patients without UC-MSCs transplantation (12% VS 2.2%). The survival percentage was improved by treatment with UC-MSCs transplantation compared with non-UC-MSCs transplantation in ESLD patients during the five years follow-up. The inflammation and fibrosis scores were decreased in the ESLD patients with UC-MSCs transplantation. The liver cirrhosis was largely improved, and Child-Pugh scores were decreased. Conclusions: UC-MSCs transplantation is able to decrease the risks of liver cancers in ELSD patients. The reduction of liver cancer incidence might be related to decrease of inflammation by UC-MSCs transplantation. More efforts should be investigated towards increasing the number of patients and follow-up time to further verify the therapeutic benefits of UC-MSCs translations in treating liver cancers.

CD133+ Pluripotent Stem Cells for the Treatment of Chronic Liver Failure.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1185-1185
Author(s):  
Lucia Catani ◽  
Stefania Lorenzini ◽  
Rosaria Giordano ◽  
Paolo Caraceni ◽  
Maria Rosa Motta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Chronic Liver ◽  
Peripheral Blood Stem Cells ◽  
End Stage Liver Disease ◽  
End Stage

Abstract Abstract 1185 Background. The potential role of bone marrow (BM)-derived stem cells (SCs) in patients with end-stage liver disease has been addressed by our group in four studies. Main objectives were: 1) to assess stem/progenitor cell mobilization in 24 patients receiving orthotopic liver transplantation (OLT); 2) to evaluate whether G-CSF can be safely administered to patients with liver cirrhosis in order to expand and mobilize BM-derived SCs; 3) to investigate the effects of transplantation of human G-CSF-mobilized CD34+ and CD133+ SCs in mice with chronic liver injury and fibrosis; 4) to evaluate the feasibility and the safety of the purification and intrahepatic reinfusion of increasing numbers of autologous BM-derived G-CSF-mobilized CD133+ SCs in patients with end-stage liver disease. Methods. 1) Flow cytometry analysis, clonogenic assays and RT-PCR have been performed after OLT; 2) 18 patients with advanced liver disease were consecutively treated with increasing doses of G-CSF starting from 2 μg/kg/daily; 3) C57BL/6N mice received CCl4 by inhalation for thirteen weeks and were treated with Cyclosporin-A. Transplantation was performed by injection (tail vein) of 106 CD34+ or CD133+ SCs of three cirrhotic patients. After four weeks from transplantation all mice were sacrificed; 4) G-CSF at 7.5μg/Kg/b.i.d. is administered subcutaneosly (sc) from day 1 until the completion of peripheral blood stem cells (PBSC) collection. Collection of PBSC will begin on day + 4 only if the concentration of CD133+ cells is 38/mL. PB mononuclear cells obtained from mobilized standard-volume leukapheresis will be incubated with Macs colloidal superparamagnetic CD133 microbeads. CliniMacs device is used for the positive selection of CD133+ SCs under GMP conditions. At least 4 weeks after SC mobilization, collection and cryopreservation, highly purified autologous G-CSF-mobilized CD133+ cells are re-infused through the hepatic artery by transfemoral or transbranchial arteriography. CD133+ cells are administered to patients starting from 5×104/Kg patient's body weight and increased every 3 patients. The maximum infused cell dose will be 1×106/kg. G-CSF at 5μg/Kg/day is administered sc for 3 days after the reinfusion of SCs for their expansion and to induce a selective proliferative advantage of reinfused cells in vivo. Results and Discussion. 1) We demonstrated that both early subsets of the hematopoietic SC compartment (CD34+/CD90+ cells) and more mature committed progenitors (CFU-C) were mobilized into PB after OLT. We also demonstrated the release from the BM of liver-committed HSCs co-expressing epithelial markers after OLT; 2) We show that the administration of G-CSF to patients with liver cirrhosis is safe and feasible and allows the mobilization and collection of BM-derived SCs at the dose of 15 mg/kg/day. 3) We demonstrated that mice transplanted with either CD133+ or CD34+ human cells appear to have less fibrotic septa than mice without SC transplantation, suggesting the potential therapeutic role of human SCs on the recovery of liver fibrosis. 4) Up to date, three patients with end stage liver disease have been successfully mobilized with G-CSF and highly purified autologous CD133+ SCs have been re-infused. The number of collected CD133+ SCs is 0,7, 0,2 and 0.35×106/Kg, respectively. The number of the re-infused highly purified CD133+ SCs is 4.7, 5.0 and 5.4×104/Kg, respectively. No adverse events have been recorded during mobilization or intrahepatic SCs re-infusion. Updated results on current patients and future patients will be presented at the Meeting. Disclosures: No relevant conflicts of interest to declare.

Πειραματική απομόνωση και μεταμόσχευση μεσεγχυματικών κυττάρων (mesenchymal stem cells-msc) σε πειραματικό πρότυπο 50-60% ηπατεκτομής σε αρουραίους

2018 ◽  
Author(s):  
Ιωάννης Παπανικολάου
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Liver Disease ◽  
End Stage Liver Disease ◽  
End Stage

Σκοπός: Η παρούσα πειραματική διδακτορική διατριβή είχε ως στόχο να καταδείξει εάν η μεταμόσχευση μεσεγχυματικών βλαστικών κυττάρων δύναται να ενισχύσει την φυσιολογική αναγέννηση του ήπατος που αναμένεται μετά από μερική ηπατεκτομή, να αποτρέψει την εμφάνιση οξείας ηπατικής ανεπάρκειας η οποία ακολουθεί συχνά ιδίως μετά από μείζονες ηπατεκτομές και να βελτιώσει την ιστοπαθολογική βλάβη. Ο ρόλος των μεσεγχυματικών βλαστικών κυττάρων έχει μελετηθεί σε αρκετές πρόσφατες πειραματικές εργασίες και διαφαίνεται λίαν ελπιδοφόρος. Υλικά και Μέθοδοι: Βλαστικά κύτταρα λιπώδους ιστού, ADSCs (Adipose tissue-derived Mesenchymal Stem Cells - MSCs), απομονώθηκαν, συντηρήθηκαν σε κυτταροκαλλιέργειες και ακολούθως μεταμοσχεύθηκαν είτε ενδοφλέβια στην πυλαία φλέβα είτε απευθείας στο ηπατικό παρέγχυμα (ενδοηπατικά). Ακολούθησε φθορίζoντας in situ υβριδισμός (FISH) με στόχο την ανίχνευση των μεταμοσχευμένων βλαστικών κυττάρων στο ηπατικό παρέγχυμα. Προκειμένου να αξιολογήσουμε το ρόλο των βλαστικών κυττάρων στην ενίσχυση της ηπατικής αναγέννησης μετά από μερική ηπατεκτομή, διενεργήσαμε κλασική παθολογοανατομική μελέτη με χρήση score στον ιστό και ακολούθως, ανοσοϊστοχημεία για τους παράγοντες HGF και HNF4a. Αποτελέσματα: Τα βλαστικά κύτταρα ανιχνεύθηκαν στο ηπατικό παρέγχυμα όλων των πειραματόζωων. Το γεγονός αυτό αποδείχθηκε και με τη FISH, η οποία πιστοποίησε την ενσωμάτωση των βλαστικών κυττάρων στο ηπατικό παρέγχυμα. Τα επίπεδα του HGF ήταν σημαντικά υψηλότερα μεταξύ των μεταμοσχευμένων ομάδων εν συγκρίσει με την ομάδα ελέγχου. Επίσης, η διηπατική χορήγηση είχε υψηλότερα επίπεδα HGF σε σχέση με την ενδοφλέβια, όπως και η χορήγηση 2x106 MSCs σε σχέση με τη χορήγηση 1x106. Τα επίπεδα του παράγοντα ηπατικής διαφοροποίησης HNF4a, αυξήθηκαν σημαντικά μετά την μεταμόσχευση των βλαστικών κυττάρων. Ο HNF-4a μεταβλήθηκε στο χρόνο ενώ ο παράγων HGF, όχι. Η ομάδα διηπατικής χορήγησης παρουσίασε υψηλότερες τιμές HNF-4a, όπως και η χορήγηση 2x106 MSCs. Τα ιστοπαθολογικά αποτελέσματα καταδεικνύουν ότι οι ομάδες των μεταμοσχεύσεων αν και δε διαφοροποιούνται με στατιστική σημαντικότητα μεταξύ τους, εμφανίζουν χαμηλότερα σκορ ιστοπαθολογικής βλάβης σε σχέση με την ομάδα control. Συμπέρασμα: Η πειραματική αυτή μελέτη αποδεικνύει ότι η μεταμόσχευση των βλαστικών κυττάρων λιπώδους ιστού ενισχύει την αναμενόμενη ηπατική αναγέννηση μετά από μερική ηπατεκτομή και δύναται να αποτελέσει ένα ελπιδοφόρο μέσο για την πρόληψη της οξείας ηπατικής ανεπάρκειας και την αντιμετώπιση της νόσου τελικού σταδίου του ήπατος (ESLD – end stage liver disease).

scholarly journals Peripheral vein infusion of autologous mesenchymal stem cells in Egyptian HCV-positive patients with end-stage liver disease

2014 ◽  
Vol 5 (3) ◽  
pp. 70 ◽  
Author(s):  
Hosny Salama ◽  
Abdel-Rahman N Zekri ◽  
Eman Medhat ◽  
Shereen A Al Alim ◽  
Ola S Ahmed ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Disease ◽  
Peripheral Vein ◽  
End Stage Liver Disease ◽  
Autologous Mesenchymal Stem Cells ◽  
End Stage

scholarly journals Creatinine-modified Child-Turcotte-Pugh score is a good predictor of a short-term survival in patients with bleeding from esophageal varices

2017 ◽  
Vol 74 (1) ◽  
pp. 13-18
Author(s):  
Mirjana Radisavljevic ◽  
Goran Bjelakovic ◽  
Jasna Jovic ◽  
Biljana Radovanovic-Dinic ◽  
Danijela Benedeto-Stojanov ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Esophageal Varices ◽  
Meld Score ◽  
Prognostic Scores ◽  
Short Term ◽  
End Stage Liver Disease ◽  
Ctp Score ◽  
End Stage

Background/Aim. Bleeding from esophageal varices is a significant factor in mortality of patients with terminal liver cirrhosis. This complication is a major health problem for recipients on the list for liver transplant. In that regard, studying predictors of variceal bleeding episode is very important. Also, it is important to find the best survival predictor among prognostic scores. The aim of the study was to compare validity of prognostic scores in assessment of survival in hospital-treated patients after bleeding from esophageal varices, and to compare validity of baseline Child-Turcotte-Pugh (CTP) and Modul for End-stage Liver Disease (MELD) scores with CTP creatinine modified (CTP-crea) I and II scores in assessment of survival in patients within a long-term follow-up period after the episode of bleeding from esophageal varices. Methods. The study included a total of 126 patients suffering from terminal liver cirrhosis submited to testing CTP score score I and II, MELD score, MELD Na score, integrated MELD score, MELD sodium (MESO) index, United Kingdom Model for End-Stage Liver Disease (UKELD) score and updated MELD score. Results. Patients with bleeding from esophageal varices most often had CTP score rank C (46,9%). CTP score rank B had 37.5% patients, while the smallest percentage of patients had CTP rank A, 15.6% of them. Patients who have values of CTP score higher than 10.50 and bleeding from esophagus, have 3.2 times higher chance for death outcome compared to other patients. Patients who have values of CTP-crea I score higher than 10.50 and bleeding from esophagus, have 3.1 times higher chance for death out-come than other patients. Patients who have values of CTP-crea II score higher than 11.50 and bleeding from esophagus, have 3,7 times higher chance for death outcome compared to other patients. Conclusion. Survival of patients with bleeding from esophageal varices in the short-term follow up can be predicted by following CTP score and creatinine modified CTP scores. Patients with bleeding from esophageal varices who have CTP score and CTP-crea I score higher than 10.5 and CTP-crea II score higher than 11.5, have statistically significantly higher risk from mortality within one-month follow-up compared to patients with bleeding from esophageal varices who have lower numerical values of scores of the CTP group.

scholarly journals Doppler ultrasound in liver cirrhosis: correlation of hepatic artery and portal vein measurements with model for end-stage liver disease score in Egypt

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Ahmed Abdelrahman Mohamed Baz ◽  
Rana Magdy Mohamed ◽  
Khaled Helmy El-kaffas
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Portal Vein ◽  
Hepatic Artery ◽  
Meld Score ◽  
Hepatic Decompensation ◽  
End Stage Liver Disease ◽  
Cirrhotic Patients ◽  
Us Findings ◽  
End Stage

Abstract Background Liver cirrhosis is a multi-etiological entity that alters the hepatic functions and vascularity by varying grades. Hereby, a cross-sectional study enrolling 100 cirrhotic patients (51 males and 49 females), who were diagnosed clinically and assessed by model for end-stage liver disease (MELD) score, then correlated to the hepatic Doppler parameters and ultrasound (US) findings of hepatic decompensation like ascites and splenomegaly. Results By Doppler and US, splenomegaly was evident in 49% of patients, while ascites was present in 44% of them. Increased hepatic artery velocity (HAV) was found in70% of cases, while 59% showed reduced portal vein velocity (PVV). There was a statistically significant correlation between HAV and MELD score (ρ = 0.000), but no significant correlation with either hepatic artery resistivity index (HARI) (ρ = 0.675) or PVV (ρ =0.266). Moreover, HAV had been correlated to splenomegaly (ρ = 0.000), whereas HARI (ρ = 0.137) and PVV (ρ = 0.241) did not significantly correlate. Also, ascites had correlated significantly to MELD score and HAV (ρ = 0.000), but neither HARI (ρ = 0.607) nor PVV (ρ = 0.143) was significantly correlated. Our results showed that HAV > 145 cm/s could confidently predict a high MELD score with 62.50% and 97.62 % sensitivity and specificity. Conclusion Doppler parameters of hepatic vessels (specifically HAV) in addition to the US findings of hepatic decompensation proved to be a non-invasive and cost-effective imaging tool for severity assessment in cirrhotic patients (scored by MELD); they could be used as additional prognostic parameters for improving the available treatment options and outcomes.

Groin Herniorrhaphy in Patients with Cirrhosis and after Liver Transplantation

2009 ◽  
Vol 75 (10) ◽  
pp. 962-965
Author(s):  
Elise H. Lawson ◽  
Elizabeth Benjamin ◽  
Ronald W. Busuttil ◽  
Jonathan R. Hiatt
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
International Normalized Ratio ◽  
Wound Complications ◽  
End Stage Liver Disease ◽  
Proper Patient Selection ◽  
Cirrhotic Patients ◽  
End Stage ◽  
Cirrhotic Group

We report on 43 groin herniorrhaphy operations, 18 in 18 patients with documented cirrhosis and 25 in 24 patients after liver transplantation (LT), over a 10-year period at UCLA. Average follow up was 33 months. Most patients were males (84%) with reducible inguinal hernias (70%). Child's class of cirrhotic patients was B in 66 per cent and A and C in 17 per cent each; 7 patients (39%) went on to LT. Compared with post-LT patients, patients with cirrhosis had significantly lower platelets and significantly higher bilirubin, international normalized ratio, and Model for End-stage Liver Disease scores. Mesh was used in 33 per cent of the cirrhotic group and 48 per cent of the LT group. There were four minor wound complications but no deaths, major complications, infections, or ascitic leaks in either group. Two hernias recurred in the cirrhosis group (11%) and none after LT. We conclude that with proper patient selection, groin herniorrhaphy with or without mesh is a safe and durable procedure in patients with cirrhosis and after LT. This is the first large series of groin herniorrhaphy after LT.

The 1-year and 3-month prognostic utility of the AST/ALT ratio and model for end-stage liver disease score in patients with viral liver cirrhosis

2002 ◽  
Vol 97 (11) ◽  
pp. 2855-2860 ◽  
Author(s):  
Edoardo Giannini ◽  
Federica Botta ◽  
Emanuela Testa ◽  
Paola Romagnoli ◽  
Simone Polegato ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Disease Score ◽  
End Stage Liver Disease ◽  
Prognostic Utility ◽  
End Stage
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