Table 1.
Clinical trials in liver diseases
| No. | Start year | Cell source | Autologous/allogeneic | Administration route | Number of cells infused | Etiology | Number of patients | Follow-up period | Phase | Study design | ClinicalTrials.gov identifier | Status | Result | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2013 | Bone marrow | Autologous | Peripheral vein | Unknown | LC | 20 | 48 weeks | Phase 1–2 | Non-randomized, single group assignment, open label | NCT01877759 | Unknown | ||
| 2 | 2009 | Bone marrow | Autologous | Hepatic artery | 5 × 106 cells/patient, 2 times | LC (alcohol) | 11 | 24 weeks | Phase 2 | Non-randomized, single group assignment, open label |
NCT01741090 | Unknown | Histological improvement. Improvement in Child- Pugh score. Decrease in TGFβ1, collagen type I, and α-SMA |
|
| 3 | 2009 | Bone marrow | Autologous | Peripheral vein | 1.0 × 106/kg | LC | 25 | 24 weeks | Unknown | Non-randomized, single group assignment, open label | NCT01499459 | Unknown | Improvement in Alb and MELD scores. | 13 |
| 4 | 2014 | Umbilical cord | Allogeneic | Peripheral vein | 4.0 × 107/patient, 4 times | LC | 320 | 144 weeks | Phase 1–2 | Non-randomized, parallel assignment, open label | NCT01573923 | Unknown | ||
| 5 | 2016 | Adipose tissue | Autologous | Portal vein or hepatic artery | 1.0 × 106/kg via peripheral vein, 3 times or 3.0 × 106/kg via hepatic artery, 3 times | LC (HCV) | 5 | 48 weeks | Phase 1–2 | Non-randomized, single group assignment, open label | NCT02705742 | Recruiting | ||
| 6 | 2007 | Bone marrow | Autologous | Peripheral or portal vein | 30–50 × 106/patient | LC | 8 | 24 weeks | Phase 1–2 | Randomized, single group assignment, single blind | NCT00420134 | Completed | Improvement in liver function and MELD scores. | 14 |
| 7 | 2016 | Bone marrow | Allogeneic | Peripheral vein | 2.0 × 106/kg, 4 times | ACLF | 30 | 96 weeks | Phase 1 | Randomized, parallel assignment, double blind (subject, caregiver, investigator) | NCT02857010 | Recruiting | ||
| 8 | 2009 | Umbilical cord | Allogeneic | Peripheral vein | 5.0 × 105/kg, 3 times | ACLF (HBV) | 43 | 96 weeks | Phase 1–2 | Randomized, parallel assignment, double blind (subject, caregiver) | NCT01218464 | Unknown | Improvement in liver function and MELD scores. | 15 |
| 9 | 2011 | Bone marrow | Allogeneic | Peripheral vein | 2.0 × 105/kg, 4 times or 1.0 × 106/kg, 4 times or 5.0 × 106/kg, 4 times | Liver failure (HBV) | 120 | 48 weeks | Phase 2 | Randomized, parallel assignment, open label | NCT01322906 | Unknown | ||
| 10 | 2010 | Umbilical cord | Allogeneic | Unknown | Unknown | LC | 20 | 48 weeks | Phase 1–2 | Randomized, parallel assignment, open label | NCT01342250 | Completed | ||
| 11 | 2012 | Bone marrow | Allogeneic | Hepatic artery | Unknown | LC (Alcohol) | 40 | 96 weeks | Phase 2 | Randomized, parallel assignment, open label | NCT01591200 | Completed | ||
| 12 | 2012 | Umbilical cord | Allogeneic | Peripheral vein | 1.0 × 105/kg, 4 times | Liver failure (HBV) | 120 | 48 weeks | Phase 1–2 | Randomized, parallel assignment, open label | NCT01724398 | Unknown | ||
| 13 | 2016 | Bone marrow | Autologous | Portal vein | 2.0 × 106/kg | LC | 40 | 24 weeks | Phase 1–2 | Non-randomized, parallel assignment, open label | NCT02943889 | Not yet recruiting | ||
| 14 | 2009 | Umbilical cord | Allogeneic | Portal vein or hepatic artery | Unknown | LC | 200 | 48 weeks | Phase 1–2 | Randomized, parallel assignment, single blind (subject) | NCT01233102 | Suspended | ||
| 15 | 2009 | Bone marrow | Autologous | Portal vein | Unknown | LC (HBV) | 60 | 48 weeks | Phase 2 | Non-randomized, parallel assignment, open label | NCT00993941 | Unknown | ||
| 16 | 2010 | Umbilical cord | Allogeneic | Hepatic artery | Unknown | LC | 50 | 4 weeks | Phase 1–2 | Randomized, parallel assignment, open label | NCT01224327 | Unknown | ||
| 17 | 2013 | Bone marrow | Autologous | Hepatic artery | 1.0 × 106/kg | LC | 30 | 12 weeks | Phase 3 | Non-randomized, single group assignment, open label | NCT01854125 | Enrolling by invitation | ||
| 18 | 2012 | Umbilical cord | Allogeneic | Hepatic artery | 1.0 × 106/kg | LC (HBV) | 240 | 48 weeks | Phase 1–2 | Randomized, parallel assignment, open label | NCT01728727 | Unknown | ||
| 19 | 2013 | Umbilical cord or bone marrow | Allogeneic | Peripheral vein | 1.0 × 105/kg, 1.0 × 106/kg or 1.0 × 107/kg, 8 times | Liver failure (HBV) | 210 | 72 weeks | Phase 1–2 | Randomized, parallel assignment, open label | NCT01844063 | Recruiting | ||
| 20 | 2016 | Umbilical cord | Allogeneic | Peripheral vein | 4 or 8 times | ACLF (HBV) | 261 | 52 weeks | Phase 2 | Randomized, parallel assignment, open label | NCT02812121 | Not yet recruiting | ||
| 21 | 2010 | Menstrual blood | Allogeneic | Peripheral vein | 1.0 × 106/kg, 4 times | LC | 50 | 48 weeks | Phase 1–2 | Randomized, single group assignment, open label | NCT01483248 | Enrolling by invitation | ||
| 22 | 2008 | Bone marrow | Autologous | Hepatic artery | Unknown | LC | 50 | 96 weeks | Phase 2 | Randomized, parallel assignment, single blind (subject) | NCT00976287 | Unknown | ||
| 23 | 2012 | Bone marrow | Autologous | Hepatic artery | 5 × 107/patient, 1 time or 2 times | LC (alcohol) | 72 | 24 weeks | Phase 2 | Randomized, parallel assignment, open label | NCT01875081 | Completed | Histological improvement. Improvement in AST, ALT, ALP, γ-GTP, Child-Pugh score, and MELD score. | 16 |
| 24 | 2014 | Bone marrow | Autologous | Peripheral vein | Unknown | LC | 10 | 24 weeks | Phase 1 | Non-randomized, single group assignment, open label | NCT02327832 | Recruiting | ||
| 25 | 2005 | Bone marrow | Autologous | Hepatic artery | 3.4 × 108/patient | Liver failure (HBV) | 158 | 192 weeks | Phase 1–2 | Case control, retrospective | NCT00956891 | Completed | Improvement in Alb, T-Bil, PT, and MELD score. | |
| 26 | 2009 | Umbilical cord | Allogeneic | Peripheral vein | 5.0 × 105/kg, 3 times | LC | 45 | 48 weeks | Phase 1–2 | Randomized, parallel assignment, open label | NCT01220492 | Unknown | Improvement in Alb, T-Bil, and MELD score. Reduction of ascites. |
17 |
| 27 | 2010 | Bone marrow | Autologous | Portal vein | 1.4–2.5 × 108/patient, 2 times | LC | 2 | 48 weeks | Phase 1 | Non-randomized, single group assignment, open label | NCT01454336 | Completed | Transient improvement in MELD scores. | 18 |
| 28 | 2007 | Bone marrow | Autologous | Peripheral vein | (1.2–2.95 × 108) 1.95 × 108/patient | LC | 27 | 48 weeks | Unknown | Randomized, parallel assignment, double blind (subject, outcomes assessor) |
NCT00476060 | Unknown | No beneficial effect. | 19 |
| 29 | 2011 | Bone marrow | Allogeneic | Hepatic artery and peripheral artery | 1.0 × 106/kg (5.0 × 107 cells via the hepatic artery and the remaining cells via the peripheral vein) | Wilson’s disease | 10 | 24 weeks | Unknown | Non-randomized, single group assignment, open label | NCT01378182 | Completed | ||
| 30 | 2016 | Umbilical cord or bone marrow | Allogeneic | Portal vein or hepatic artery | 2.0 × 107/patient, 4 times | LC | 20 | 48 weeks | Phase 1 | Non-randomized, single group assignment, open label | NCT02652351 | Recruiting | ||
| 31 | 2016 | Bone marrow | Autologous | Hepatic artery | 5 × 107/patient, 1 time or 2 times | LC (alcohol) | 50 | 144 weeks | Phase 2 | Randomized, parallel assignment, open label | NCT02806011 | Enrolling by invitation | ||
| 32 | 2011 | Umbilical cord | Allogeneic | Peripheral vein | 1.0 × 106/kg, 3 times | Liver failure (AIH) | 100 | 96 weeks | Phase 1–2 | Randomized, parallel assignment, open label | NCT01661842 | Unknown | ||
| 33 | 2009 | Adipose tissue | Autologous | Unknown | Unknown | LC | 6 | 24 weeks | Phase 1 | Non-randomized, single group assignment, open label | NCT00913289 | Terminated | ||
| 34 | 2012 | Adipose tissue | Autologous | Hepatic artery | Unknown | LC | 4 | 4 weeks | Unknown | Non-randomized, single group assignment, open label | NCT01062750 | Completed | ||
| 35 | 2016 | Umbilical cord | Allogeneic | Lobe | 5.0 × 108/patient | LC | 40 | 96 weeks | Phase 1–2 | Randomized, parallel assignment, double blind (subject, outcomes assessor) | NCT02786017 | Recruiting | ||
| 36 | 2011 | Bone marrow | Unknown | Peripheral vein | 5.0–50 × 106/kg | LC (PBC) | 20 | 96 weeks | Phase 1 | Randomized, parallel assignment, open label | NCT01440309 | Unknown | ||
| 37 | 2011 | Umbilical cord | Allogeneic | Peripheral vein | 5.0 × 105/kg, 3 times | LC (PBC) | 7 | 48 weeks | Phase 1–2 | Randomized, parallel assignment, open label | NCT01662973 | Unknown | Improvement in Alb, T-Bil, and MELD score. Reduction of ascites. | 20 |
| 38 | 2010 | Bone marrow | Allogeneic | Portal vein or hepatic artery | Unknown | Liver failure (HBV) | 60 | 48 weeks | Phase 2 | Non-randomized, parallel assignment, open label | NCT01221454 | Unknown | ||
| 39 | 2010 | Bone marrow | Allogeneic | Portal vein or hepatic artery | Unknown | LC | 60 | 48 weeks | Phase 2 | Non-randomized, parallel assignment, open label | NCT01223664 | Unknown | ||
| 40 | 2010 | Bone marrow | Autologous | Hepatic artery | (0.25–1.25 × 106) 0.75 × 106/patient | LC (HBV) | 39 | 24 weeks | Phase 2–3 | Non-randomized, parallel assignment, open label | NCT01560845 | Unknown | Decrease in Th-17 cells, RORγt, IL-17, TNF-α, and IL-6. Increase in Tregs and Foxp3. | 21 |
LC liver cirrhosis, ACLF acute-on-chronic liver failure, HBV hepatitis B virus, HCV hepatitis C virus, AIH autoimmune hepatitis, PBC primary biliary cholangitis, MELD Model for End-Stage Liver Disease, AST aspartate transaminase, ALT alanine transaminase, ALP alkaline phosphatase, γ-GTP gamma-glutamyl transpeptidase, Alb albumin, T-bill total bilirubin, PT prothrombin time, PC protein C, ROR RAR-related orphan receptor, Foxp3 forkhead box P3, IL interleukin, Th T helper, SMA smooth muscle actin, TGF transforming growth factor, TNF tumor necrosis factor