Table 2.
Clinical trials using MSCs to treat liver disease
| Liver disease | MSCs source | Injection route | Enrolled patients | Cell doses | Follow-up | Clinical results | References |
|---|---|---|---|---|---|---|---|
| Decompensated liver cirrhosis | UC-MSCs | Vein | Control group (n = 15)/MSCs treatment group (n = 30) | 0.5 × 106/kg | 48 weeks | Significantly reduced the volume of ascites and improvement of liver function (increased of serum albumin levels, decrease in total serum bilirubin levels, and decreased in the sodium model for end-stage liver disease scores) | Zhang et al. [52] |
| Liver cirrhosis | AD-MSCs | Liver | Pre-MSCs therapy group (n = 6)/Post-MSCs therapy group (n = 6) | 1.0 × 108 | 6 months | Significantly improved liver function, METAVIR score, Child–Pugh score, MELD score, and quality of life for patients with liver cirrhosis | Huang et al. [53] |
| Alcoholic cirrhosis | BM-MSCs | Hepatic artery | Pre-MSCs therapy group (n = 11)/Post-MSCs therapy group (n = 11) | 5.0 × 107/kg | 12 weeks | Improved histological features and Child–Pugh score, decreased transforming growth factor-β1, type 1 collagen and α-smooth muscle actin level | Jang et al. [54] |
| Alcoholic cirrhosis | BM-MSCs | Hepatic artery | Control group (n = 18)/One-time MSCs group (n = 18)/Two-time MSCs group (n = 19) | 5.0 × 107/kg | 12 months | Improved tissue fibrosis (reduction in the proportion of collagen) and liver function (improvement of the Child–Pugh scores) | Suk et al. [55] |
| HCV-positive patients with end-stage liver disease | BM-MSCs | Peripheral vein | MSCs transplantation group (n = 20)/Control group (n = 20) | 1.0 × 106/kg | 26 weeks | Improved liver synthetic functions (improved ALT, AST and S-albumin levels, as well as the Child–Pugh score and performance score) and hepatic fibrosis (decreased the serum levels of the hepatic fibrosis markers, PIIICP and PIIINP) | Salama et al. [56] |
| Primary biliary cirrhosis with a suboptimal response to UDCA treatment | UC-MSCs | Peripheral vein | Primary biliary cirrhosis patients with a suboptimal response to UDCA treatment (n = 7) | 0.5 × 106/kg | 48 weeks | Improved liver function (serum alkaline phosphatase and γ-glutamyltransferase levels decreased) and clinical symptoms (fatigue and pruritus were alleviated) | Wang et al. [57] |
| Liver cirrhosis caused by autoimmune diseases | BM-MSCs, UC-MSCs and cord blood-MSCs (CB-MSCs) | Peripheral vein | UC-MSCs transplantation group (n = 23)/ CB-MSCs transplantation group (n = 2)/BM-MSCs transplantation group (n = 1) | 1.0 × 106/kg | 2 years | Reduced the mean total bilirubin and prothrombin time, improved the average serum albumin levels and MELD score, without serious adverse events | Liang et al. [58] |
| Decompensated liver cirrhosis after splenectomy | Autologous bone marrow | Portal vein | Autologous bone marrow transfusion group (n = 15)/Control group (n = 10) | 1.0–2.0 × 106/kg | 6 months | Improved liver function (improved ALB, ALT, and cholinesterase levels and decreased liver stiffness measurement and AFP) | Zhang et al. [59] |
| ACLF | BM-MSCs | Peripheral vein | Stem cell group (n = 4)/Placebo group (n = 5) | 1.0 × 106/kg | 90 days | Improved Child–Pugh score, MELD, and ACLF classification | Schacher et al. [60] |
| HBV-related ACLF | BM-MSCs | Peripheral vein | Standard medical therapy group (n = 54)/MSCs transplantation group (n = 56) | 1.0–10 × 105/kg | 24 weeks | Improved liver function, decreased the incidence of severe infection, and significantly improved the 24-week survival rate | Lin et al. [61] |
| HBV-related ACLF | UC-MSCs | Cubital vein | MSCs transplantation group (n = 24)/Control group (n = 19) | 0.5 × 106/kg | 72 weeks | Partially improved liver function (improve serum total bilirubin and Model for End-Stage Liver Disease scores), reduced the incidence of severe infections (reduce the incidence of severe infection, and the mortality of multiple organ failure and severe infection), and reduced patient mortality | Shi et al. [62] |
| Preparing for liver transplantation | BM-MSCs | Peripheral vein | MSCs transplantation group (n = 10)/Control group (n = 10) | 1.0–2.0 × 106/kg | 12 months | Induced mild positive changes of immunoregulatory T cells and NK cells in peripheral blood | Casiraghi et al. [63] |
| Decompensated cirrhosis | BM-MSCs | Peripheral vein | MSCs transplantation group (n = 15)/Placebo group (n = 12) | 1.95 × 108 | 12 months | No beneficial effect (no effect on the Child–Pugh score, MELD-Na score, serum albumin, INR, serum transaminases and liver volume) | Mohamadnejad et al. [64] |
| HBV-induced liver failure | BM-MSCs | Hepatic artery | MSCs transplantation group (n = 53)/Control group (n = 105) | Not mentioned | 192 weeks | Improved the short-term curative effect (improve the levels of ALB, total bilirubin, and prothrombin time and MELD score), and not improve the long-term curative effect (no effect on the incidence of HCC and mortality) | Peng et al. [65] |
| Liver cirrhosis | BM-MSCs | Peripheral vein | Pre-MSCs therapy group (n = 25)/Post-MSCs therapy group (n = 12) | 1.0 × 106/kg | 6 months | MSCs could not reach the liver in a sufficient amount | Kantarcıoğlu et al. [66] |