Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients

Abstract

Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients.

Figures

Figure 1.

Timeline of UC-MSC treatments in acute-on-chronic liver failure (ACLF) patients. UC-MSC transfusions were given to the ACLF patients three times at the baseline (0-week), 4-week, and 8-week time points. The clinical parameters were tested at the 0-, 1-, 2-, 4-, 8-, 12-, 24-, 36-, and 48-week time points during the follow-up. For survival analysis, the follow-up was prolonged to 72 weeks. Abbreviation: UC-MSC, umbilical cord-derived mesenchymal stem cell.

Figure 2.

UC-MSC treatment improved model of end-stage liver disease (MELD) scores for acute-on-chronic liver failure patients. The MELD scores were not shown to be markedly different between two groups at baseline. After UC-MSC treatment, the MELD scores were significantly decreased at weeks 4, 8, and 12 as compared with the corresponding control. Abbreviations: UC-MSC, umbilical cord-derived mesenchymal stem cell; w, week.

Figure 3.

Impact of UC-MSC transfusions on liver function. The levels of albumin, cholinesterase, prothrombin activity, total bilirubin, alanine aminotransferase, platelet count, hemoglobin, and total cholesterol were tested at the 0-, 1-, 2-, 4-, 8-, 12-, 24-, 36-, and 48-week time points. *, p < .05, **, p < .01 compared with baseline; ▵, p < .05, ▵▵, p < .01 compared with the control in the corresponding time point. Abbreviation: UC-MSC, umbilical cord-derived mesenchymal stem cell.

Figure 4.

UC-MSC transfusions improved serum α-fetoprotein (α-FP) level in one acute-on-chronic liver failure patient. (A): The level of α-FP increased after the UC-MSC transfusions (black line) but remained stable in a representative control case (blue line). (B): The levels of serum total protein, albumin, and prothrombin activity increased and total bilirubin decreased significantly compared with baseline after the UC-MSC transfusion during the follow-up period. Abbreviation: UC-MSC, umbilical cord-derived mesenchymal stem cell.

Figure 5.

UC-MSC treatments improved the survival of acute-on-chronic liver failure (ACLF) patients. Patients in the treatment group were given UC-MSC transfusions three times at 4-week intervals, whereas patients in the control group received saline infusions. All patients received the same conventional treatment throughout the study. The UC-MSC treatment increased the survival rate for ACLF patients compared with the saline-treated controls. Abbreviation: UC-MSC, umbilical cord-derived mesenchymal stem cell.