Table 1.
Summary of studies using stem cells for the treatment of liver diseases
| Type of stem cells | HLCs makers | Liver disease models | Outcomes | Reference |
|---|---|---|---|---|
| Rhesus monkey ESCs | AFP, ALB, HNF4, CK8 and CK19 | Rhesus monkey ESCs derived cells displayed hepatic characteristics | Kuai et al. [16] | |
| Human ESCs |
CYP3A4, CYP1A2, CYP2C9, 1-antitrypsin, FP, HNF4, MRP2 and OATP2 |
HLCs generated from human ESCs had liver-like properties | Brolén et al. [17] | |
| Human ESCs | ALB, keratin 18, keratin 7 and Keratin19 | Mice with CCl4 induced acute liver injury | Recovery of injured liver tissues in mice model | Woo et al. [18] |
| human ESC (VAL9) | ALB, CYP3A4, CD81, CLDN1 and ASGR | Mice with acetaminophen-induced acute liver failure | Repopulate the liver and rescue the liver function | Tolosa et al. [19] |
| Mouse ESCs | ALB, AFP, CYP7A1 | Mice with CCl4 induced acute liver injury |
Establish a nanoparticles-based delivery system for growth factors Differentiated HLCs significantly restored the injured liver |
Wang et al. [20] |
| Mouse iPSCs | ALB, AFP | HLCs displayed key liver functions and can integrate into the hepatic parenchyma in vivo | Si‐Tayeb et al. [26] | |
| Human iPSCs | HNF4A, AFP, RBP4, TTR, ALB | Mice with ganciclovir induced liver failure | Vascularized and functional human liver was generated by transplantation of human iPSCs-LBs | Takebe et al. [28] |
| Human LSCs | Tgfb1 and Fgf1 | Mice with CCl4 induced subacute liver injury | hFLMPCs can engraft and repair injured liver | Irudayaswamy et al. [33] |
| HPCs | HNF4α and CYP2D6 | AhCre+Mdm2flox/flox mice | Transplanted HPCs restored liver parenchyma and regenerated hepatocytes and biliary epithelia. | Lu et al. [35] |
| Mouse LSCs | Hnf4-a positive and Krt19 negative | Mice with CCl4 induced liver injury | Lgr5+ stem cells can generate hepatocytes and biliary duct cells during the repair phase | Huch et al. [36] |
| Rat BM-MSCs | ALB, AST, ALP | Acetaminophen liver injury | BM-MSCs enhanced hepatocyte regeneration, and inhibited liver stress and inflammatory signaling | Dowidar [43] |
| Human AT-MSCs | AFP, ALB | Mice with CCl4 induced liver injury | AT-MSCs can relieve the impairment of injured livers | Yin et al. [44] |
| Human BM-MSCs | ALT, AST | Mice With Lethal Fulminant Hepatic Failure | hiPSC-MSCs had therapeutic effect in the mouse AHF |
Salama et al. [46] model |
| Allogeneic BM-MSCs | ALT, AST | Patients with ursodeoxycholic acid resistant primary biliary cirrhosis | Life quality of the patients was improved after BM-MSC transplantation | Wang et al. [47] |
| BM-MSCs | Patients with alcohol-related hepatic fibrosis | BM-MSCs therapy induced a histological and quantitative improvement of hepatic fibrosis |
Jang et al. [48] |
|
| Pancreatic progenitor-like cell | CYP3A4, CPSI and ALB | B-13 progenitor cell can generate hepatocytes with genetic alterations | Fairhall et al. [66] |
ESCs: embryonic stem cells; ASCs: adult stem cells; iPSCs: induced pluripotent stem cells; HPCs: hepatic progenitor cells; MSCs: mesenchymal stem cells; LSCs: liver stem cells; BM-MSCs: bone marrow-derived mesenchymal stem cells; AT-MSCS: adipose tissue-derived mesenchymal stem cells; AFP: α-fetoprotein; ALB: albumin; HNF4: hepatocyte nuclear factor 4; CK8: cytokeratin 8; CK19: cytokeratin 19; AST: aspartate aminotransferase; ALT: alanine aminotransferase; ASGR: asialoglycoprotein receptor; RBP44: retinol binding protein 4; TTR: transthyretin; Tgrb-1: transforming growth factor beta 1, Fgf1: fibroblast growth factor 1; ALP: alkaline phosphatase; CPSI: carbamoyl phosphate synthetase I