Ref no Stem cell type passage dose Route Severity/other concomitant therapy Study, P-no Monitoring-outcome measures Outcome 5 T1: auto BM-MSCs–P0- T1: splenic vein-CT guidance Chronic hepatic failure, liver cirrhosis-CTP grade C, Phase I trial, BL, mo-1-2-3-4-5-6: encephalopathy, jaundice, hematemesis/melena, LL edema, ascites, ALB, TBil, DBil, SGOT, SGPT, GGT, PC, Cr, MELD score Mo-ND: no-encephalopathy ↓T1 (2/3), T2 (1/2), jaundice↓ T1 (2/5), T2 (1/4), LL edema↓ T1 (3/5) T2 (2/4), ascites↓T1 (2/3), T2 (2/3) 6 T = vancomycin IV, h-1-auto BM-MSC P2-P4, mean: IV–heparinized syringe–30 minutes Chronic liver failure, BL, d-1-4-7, wk-2-3-4, mo-2-3-6-9-12: AE, physical exam, CBC, PT, INR, s-urea, Cr, ALB, ALT, AST, ALP, TBil, dBil, AFP AE (-) 7 T =auto BM-MSCs, P4, 2x106 /kgBW, in saline, Vvol: ND, 2x, interval 40 days Hepatic A Decompensated alcoholic liver cirrhosis, CTP grade C BL, wk-6, wk 8, wk 26, wk 52: TBil, s-Alb, Cr, INR, CTP grade, diuretic use, ascites Wk 8: TBil↓, s-Alb↓, Cr↑, INR ↓, CTP score↓, diuretic use↓, ascites↓ 8 Cryopreserved– thawed (at least 4 wk) auto PB CD 133 (at least 4wk after leucapheresis)6 /kgBW Via hepatic artery–in 3 minutes End-stage liver disease-μ g/kgBW-bid-SC-5-7 days–leucapheresis from d-4 if auto PB CD μ lμ g/kg BW–3 days Phase-1 trial, During GCSF treatment: BL-d-3-4-5-6-7: PB CD 133 monitoring–no of CD 133 collected, MELD score, AE, Tbil, Cr, INR Withdraw: P-16 9 T (after leucapheresis) = auto PB CD34+ 106 (P1-P3-P5), To portal vein (P1-P2-P3) or hepatic artery (P4-P5) Chronic liver failure, WHO performance μ g SC-daily–5 days, leucapheresis T = 5 (4 M) d-1: AE d-1: PC↓ (all), but returned to baseline on d-7, nausea (5/5), pain at site (4/5), fever (1/5), vomiting (1/5), rash (1/5). 10 T = auto BM CD34+ 10x106 , purity = 95%, viability = 92.5% in 10 mL normal saline To the hepatic arter–1 mL/minutes Chronic liver failure/G-CSF (ND) 300 μ g/mL SC daily–5 days d 1-2-3-4-5: AE (fever, chills, hives, angina pectoris) AE (-) 11 T = auto CD34 depleted BM-MNC by CliniMACS-plus-fresh–cell number: ND, vehicle: ND, V vol: 310-410 ( Via hepatic artery–1200 mL/hour Liver failure waiting for OLT/standard therapy BL -d-0-7-14, mo-1-2-3-4-12: AE , s-ALB, TBil, DBil, PT, AST, ALT, s-AlP, s-HA, CTP score , LE, subj H, QoL ( ascites, liver volume , HCC) Serious AE (-), P-1–OLT at mo-4, P-3–OLT at wk-3 : CTP score ↓ (1/3), QoL ↑ (2/3), ↓(1/3), liver vol ↓(3/4), ↑(1/4) 12 T = UC-MSCs-P4, IV–3x interval 4 wk Primary biliary cirrhosis–incomplete response to UDCA/standard medication (UDCA) AE: short term, long term. AE short term: self-limiting fever (1/7)
Auto = autologous, BM = bone marrow, MSCs = mesenchymal stem cells, P0 = passage-0. CT=, IV = intranevous. Rec = recombinant, hu = human, GCSF = granulocyte colony stimulating factor, BW = body weight, bid = twice per day, SC = subcutaneous, d- = day-, PB = peripheral blood, wk = week, MNC = mononuclear cells, V vol = vehicle volume, med = median, h- = hour-, P2 = passage 2, P4 = passage 4. CTP = Child Turcotte Pugh, MELD = model of end-stage liver disease, OLT = orthotopic liver transplantation, AIH = auto immune hepatitis, UDCA = ursodeoxycholic acid. M = male, BL = base line, mo = months, LL = lower limb, ALB = albumin, Tbil = total bilirubin, Dbil = direct bilirubin, SGOT = serum glutamic oxaloacetic transaminase = AST, SGPT = serum glutamic pyruvic transaminase = ALT, GGT = gamma glutamyl transferase, PC = prothrombin concentration, AE = adverse reaction, Cr = creatinin, INR = international normalized ratio, ReI = reinfusion, QoL = quality of life, subj H = subjective healthiness, ALT = alanine aminotransferase, AST = aspartate aminotransferase, s- = serum, AlP = alkaline phosphatase, HA = hyaluronic acid, LE = liver elastography (measuring liver stiffness), CBC = complete blood count, AFP = alpha fetoprotein, PTA = prothrombin time activity, RS = risk score, USG = ultrasonography. ND = no data, no- = number of cases with – (remaining cases/base line number), Sig = significant, PR = promptly resolved, DP = disease progression, LTF = lost to follow up, P- = patient-, N = normal, FUP = follow up period, vol = volume, med = median, WBC = white blood count, HCC = hepatocellular carcinoma.
