Ref no Stem cell type passage dose, Route Severity/other concomitant therapy Study, P-no Monitoring-outcome measures Outcome 13 T: auto BM-MSC, P3-P4 median = 6 )- T: IV in 30 minutes Decompensated cirrhosis/(-) RCT BL-24 h, 1-3-6-12 mo: AE/SE: NE, MELD score, CTP score, liver function (ALB, ALT, AST, TBil, INR), PT, s-Cr, liver volume, survival AE: NE 14 T1 = auto BM-MSC-P5 T1 = T2: IV in 15 minutes-5 drops/min HCV-genotype 4, advanced cirrhosis-CTP-C, Phase II trial AE, SE: NE AE: NE 15 T: G-CSF (Neupogen, Roche)-300 μ g SC –5d+auto BM-MSCs–P0- IV End-stage liver disease, WHO performance RCT, BL-every hour-24 h-1-2-3-4-wk-2-3-4-5-6 mo: SE (fever, immune reaction, USG, Doppler, AFP),ascites, LL edema, s-bil, ALB, PT, PC, INR, ALT, AST, bU, sC, FBG, BGAM, CTP score, pcoll III, SE: (-) 16 T = auto BM-MSCs – P3, 106 cells/mL-in 10 mL normal saline To hepatic arter–over 20-30 minutes. Post hepatitis B liver failure/SMT1 Matched BL-short term (wk 1-2-3-4): AE, complication, S-RS, HoS, ALT, ALB, Tbil, PT, MELD score Adverse event (-) 17 T = auto BM-MSC, P4-P5, To hepatic artery Alcoholic cirrhosis, CTP score B-C/alcohol abstinence 6 mo before till mo12 RCT BL, every wk➔wk 52: AE AE: T2: fever 1/19 18 T: auto BM-MSC-P3 from 130-150 mL BM, dose: Infused into liver 1 mL/min Hepatitis B liver cirrhosis/antiviral (entecavir 0.5 mg/day) RCT BL, wk1-2-4-8-12-24: AE, ALT, TBil, Alb, PT, INR, MELD score, HBV DNA, Cr, serum cytokine: TNF-α , TGF-β , IL-6, IL-1, PB-MNC: Th17, Treg cells AE: T: fever (< 38.5°C) 4/20β : T > Cα , IL-6, IL-1: T < C 19 T1 = T2: Vit K 3d before transplant, auto BM-MSC➔ hepatic lineage, T1 = intrasplenic End-stage liver disease due to HCV, CTP grade C, RCT BL, wk 2, mo-1-2-4-6: SE: 24 h-fever –antipyretic ( 20 T1 = auto BM-MNC( T1: intraportal Decompensated cirrhosis waiting for LT, CTP class B or C/(-) RCT BL, mo-3, mo-6: AE, INR, Bil, AST, ALT, MELD score AE: (-) 21 T: G-CSF (Neupogen, Roche)-300 μ g-daily-SC-5d, auto BM-CD34, CD133-50 M-in100 mL saline-infusion Intraportal-ultrasound guidance End-stage liver disease, WHO performance RCT BL- every hour-24 h-wk-1-2-3-4-mo2-3-4-5-6: AE, sBil,Alb, PT, PC, INR, ALT, AST, bU, s-Cr,FBG, BGAM, CBC, CTP score, performance score, Asc,Enc, hem, HRS, survival AE: T: mild pain, discomfort-infusion site, 22 T = G-CSF (Lenograstim, Sanofi Aventis)10 μ g/kg BW–SC-5 d, To hepatic artery-in5 minutes Decompensated alcoholic liver disease, RCT BL, wk 4, wk 8, wk 12: AE; plasma TNFα , TNFα R1, IL6, AFP, HGF, TGFβ ; blood ethanol level. AE: 23 T = G-CSF 300 g (Neupogen, Roche) SC, daily–5d, LP, expanded PB-CD34 MNC– To the portal vein (if hepatopedal flow) or hepatic artery (if hepatofugal flow) Post hepatitis C advanced cirrhosis, WHO performance Allocation: atient preference, BL-mo 1-3-6-12: AE, SE: NE. AE: NE 24 T = G-CSF (ND) -5-10 μ g/kg BW-QD-SC-4d + auto PB CD34SC- 2- To hepatic artery Decompensated liver cirrhosis, CTP = grade B and C ( Controlled study, BL-4-12-24-36-48 wk: AE, symptoms: fatique, anorexia, abdominal distension, ascites; lab: ALT, AST, TBIL, ALB, PTA; CTP score, liver tumor (USG) SE: T: mild fever (2/23) -2d - resolved 25 T: Allo BM-MSCs cryopreserved at P5-P6, thawed-washed, 1- IV–infusion –in 30 minutes ACLF, MELD score 17 − 30/SMT-6 RCT, BL, immediate after infusion, 1-2-3-4-8-12-24 wk: AE (fever, rash, diarrhea), WBC, Hb, PlC, creatinine, HCC, tumor Adverse event: fever- st 4 wk, entire 24 wk: TBil, MELD score↓ T > C 26 T: fresh hu UC MSCs-P4 T: IV ACLF, MELD score = 24 ± 4 (T), OLPC, PhI/II, BL-1-2-4-8-12-24-36-48 wk: AE, symptoms: fever, edema, rash, nausea, vomiting; lab: ALT, TBIL, ALB, CHE,PTA,PC; MELD score, SE: T: mild fever (2/24)–self-limiting-12 h 27 T: hUCMSCs–cryopreserved-P3– IV-slowly–in less than 1 hour Decompensated liver cirrhosis due to hepatitis B/SMT-8 RCT BL- 2-4-8-12-24-36 wk: AE, IL 6, TNF-α ,IL10, TGF-β ,T4, Treg, T8, B cells, ALT, AST, ALB, TBil,PT,MELD, CTP score, LF, MR Adverse event (-)α (T↓ > C), IL-10 (T↑ > C)β (T↑ > C) 28 T: after 4-7 session PE–fresh UC-MSCs –P3-P4- 2× To hepatic artery–in 15 minutes HBVrACLF/ Consecutive, BL-daily-2-4-8-12-24-48-60-72-84-96 wk: AE: HCC and mortality (24mo survival) Adverse event: (-) 4wk: ALB, ALT, AST, Tbil, DBil, PT, INR, MELD score–improvement T > C ( 29 C1: FAP/BT 200 mL C1: IV Severe viral hepatitis, severe hepatic dysfunction/(-) RCT BL-follow-up time not specified: SE–rash:
T = treatment, BM-MSCs = bone marrow mesenchymal stem cells, P3 = passage-3, IV = intra venous, G-CSF = granulocyte colony stimulating factor, SC- subcutaneous, d = day/days, BW = body weight, ND = no data, C = control, MNC = mononuclear cells,HSA = human serum albumin,QD = four times a day, PB = peripheral blood,CD34SC = CD34 stem cells, auto = autologous, CT = computed tomography, wk = week/weeks, hu UC MSC = human umbilical cord mesenchymal stem cells, FAP = fresh adult plasma, BT = blood transfusion, PE = plasma exchange, UCB = umbilical cord blood, standard/supportive medical treatment-1 = SMT-1 = reduced glutathione, glycyrrhizin, ademetionine, polyenephosphatidylcholine, alprostadil, HSA, SMT-2 = close monitoring of emergency cases, if necessary: IV fluids, supplement of nutrition, zinc (for appetite), vitamin D (for osteoporosis), regular exercise to maintain muscle mass, management of pruritus, ascites, and portal hypertension, and avoidance of liver metabolized medications. IP = intraportal, BL = baseline, SMT-3 = vitamin B, calorie intake stimulation, alcohol abstinence, 4 wk prednisone 40 mg/day for severe ALD (Maddrey’s score ≥ 32), HLC = hepatocyte like cells,SMT-4 = HSA, fresh plasma, vitamin K, according to patients’ needs,SMT-5 = anti-HBV nucleoside analogue, liver protection, jaundice treatment, diuretic, SMT-6 = nutritional supplementation, HSA-10 g/day until s-Alb = 35 g/L, fresh frozen plasma (200-400 mL/day until INR = <1.5, entecavir (0.5 mg/day), S-adenosylmethionine (1.0 g/day), + treatment of complications, SMT-7 = lamivudine (100 mg daily), patients with ascites: diuretics (40 mg spironolactone +20 mg furosemide) daily, SMT-8= liver protection, liver enzyme activity and jaundice reduction, anti-HBV virus , treatment of complications, SMT-9= infusion of reduced glutathione, glycyrrhizin, ademetionine, polyenephosphatidylcholine, HSA. ACLF = acute on chronic liver failure, MELD = model of end-stage liver disease, SA = survival analysis, CTP = Child-Turcotte-Pugh, NS = no significant difference, HBVr = hepatitis C virus related, LT = liver transplantation, PEG-IFN = PEGylated Interferon α . P-no = participant number, M = male, OLPC = open labelled parallel controlled trial, ph = phase, RCT = randomized controlled trial. ALT = serum alanine aminotransferase, TBIL = total bilirubin, ALB = albumin, CHE = cholinesterase, PTA = prothrombin activity, PlC = platelet count,AST = aspartate aminotransferase, ICG-R15 = indocyanin green retension after 15 minutes, LL = lower limb, s- = serum-, Bil = bilirubin, PT = prothrombin time, PC = prothrombin concentration, INR = International normalized ratio, bU = blood urea, Cr = creatinine, F-BG = fasting - blood glucose, BGAM = blood glucose 2 hours after meal,pcoll III = procollagen III, GGT = gamma glutamyl transferase, DBil = direct bilirubin, SGOT = serum glutamic oxaloacetic transaminase = AST, SGPT = serum glutamic pyruvic transaminase = ALT, BUN = blood urea nitrogen, WBC = white blood count, NE = not evaluated, Hb = haemoglobin, HCC = hepatocellular carcinoma, LF = liver failure, MR = mortality rate, HR-QOL = health-related quality of life, CBC = complete blood count, ALP = alkaline phosphatase, HoS = hospital stay,S-RS = self-report symptoms (reduced appetite, abdominal distension, fatique),Enc = encephalopathy, Jau = jaundice, Hem/Mel = hematemesis/melena, Ed = edema, Asc = ascites, Eryt = erythema, Tremors=, Itch = itching, IBil = indirect Bil, AFP = α fetoprotein, imp = improvement, HRS = hepatorenal syndrome, HPC = hepatic progenitor cells, CEA = carcinoembryonic antigen, TG = triglycerides, TChol = total cholesterol. AE = cell therapy-related adverse event, SA = survival analysis, SE = side effect, h = hour/hours, AscR = ascites resolved, AcsD = ascites decrease, no = number of-, FDI = fever due to infection–resolved by treatment, CSR = cumulative survival rate, 1y- = 1 year-, NSD = no significant difference, SD = significant difference.
