Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease

被引:84
作者
Lyra, Andre Castro
Pereira Soares, Milena Botelho
Maia da Silva, Luiz Flavio
Fortes, Marcos Fraga
Pinheiro Silva, Andre Goyanna
de Andrade Mota, Augusto Cesar
Oliveira, Sheilla A.
Braga, Eduardo Lorens
de Carvalho, Wilson Andrade
Genser, Bernd
dos Santos, Ricardo Ribeiro
Costa Lyra, Luiz Guilherme
机构
[1] Univ Fed Bahia, Gastrohepatol Unit, BR-40296720 Salvador, BA, Brazil
[2] Hosp Sao Rafael, Salvador, BA, Brazil
[3] Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil
[4] BGStats Consulting, Graz, Austria
关键词
bone marrow; cell transplantation; liver failure; stem cell; cirrhosis;
D O I
10.3748/wjg.v13.i7.1067
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: To evaluate the safety and feasibility of bone marrow cell (BMC) transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS: Ten patients (eight males) with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS: The median age of the patients was 52 years (range 24-70 years). All patients were discharged 48 h after BMC infusion. Two patients complained of mild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 (2.19 +/- 0.9) and 4 mo (2.10 +/- 1.0) after cell transplantation that baseline levels (2.78 +/- 1.2). Albumin levels 4 mo after BMC infusion (3.73 +/- 0.5) were higher than baseline levels (3.47 +/- 0.5). International normalized ratio (INR) decreased from 1.48 (SD = 0.23) to 1.43 (SD = 0.23) one month after cell transplantation. CONCLUSION: BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease. (c) 2007 The WJG Press. All rights reserved.
引用
收藏
页码:1067 / 1073
页数:7
相关论文
共 21 条
[1]  
Ahrar Kamran, 2003, Surg Oncol Clin N Am, V12, P105, DOI 10.1016/S1055-3207(02)00089-3
[2]   Cell differentiation - Hepatocytes from nonhepatic adult stem cells [J].
Alison, MR ;
Poulsom, R ;
Jeffery, R ;
Dhillon, AP ;
Quaglia, A ;
Jacob, J ;
Novelli, M ;
Prentice, G ;
Williamson, J ;
Wright, NA .
NATURE, 2000, 406 (6793) :257-257
[3]   Stem cells for the treatment of liver disease [J].
Allen, KJ ;
Buck, NE ;
Williamson, R .
TRANSPLANT IMMUNOLOGY, 2005, 15 (02) :99-112
[4]   Cellular origin of regenerating parenchyma in a mouse model of severe hepatic injury [J].
Braun, KM ;
Sandgren, EP .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 157 (02) :561-569
[5]   Systemic infusion of FLK1+ mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice [J].
Fang, BJ ;
Shi, MX ;
Liao, LM ;
Yang, SG ;
Liu, YH ;
Zhao, RC .
TRANSPLANTATION, 2004, 78 (01) :83-88
[6]   Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease [J].
Gaia, Silvia ;
Smedile, Antonina ;
Omede, Paola ;
Olivero, Antonella ;
Sanavio, Fiorella ;
Balzola, Federico ;
Ottobrelli, Antonio ;
Abate, Maria Lorena ;
Marzano, Alfredo ;
Rizzetto, Mario ;
Tarella, Corrado .
JOURNAL OF HEPATOLOGY, 2006, 45 (01) :13-19
[7]   Characterization and clinical application of human CD34+ stem/progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor [J].
Gordon, Myrtle Y. ;
Levicar, Natasa ;
Pai, Madhava ;
Bachellier, Philippe ;
Dimarakis, Ioannis ;
Al-Allaf, Faisal ;
M'Hamdi, Hanane ;
Thalji, Tamara ;
Welsh, Jonathan P. ;
Marley, Stephen B. ;
Davies, John ;
Dazzi, Francesco ;
Marelli-Berg, Federica ;
Tait, Paul ;
Playford, Raymond ;
Jiao, Long ;
Jensen, Steen ;
Nicholls, Joanna P. ;
Ayav, Ahmet ;
Nohandani, Mahrokh ;
Farzaneh, Farzin ;
Gaken, Joop ;
Dodge, Rikke ;
Alison, Malcolm ;
Apperley, Jane F. ;
Lechler, Robert ;
Habib, Nagy A. .
STEM CELLS, 2006, 24 (07) :1822-1830
[8]  
Haque S, 1996, LAB INVEST, V75, P699
[9]   Hematopoietic stem cells convert into liver cells within days without fusion [J].
Jang, YY ;
Collector, MI ;
Baylin, SB ;
Diehl, AM ;
Sharkis, SJ .
NATURE CELL BIOLOGY, 2004, 6 (06) :532-539
[10]   Purified hematopoietic stem cells can differentiate into hepatocytes in vivo [J].
Lagasse, E ;
Connors, H ;
Al-Dhalimy, M ;
Reitsma, M ;
Dohse, M ;
Osborne, L ;
Wang, X ;
Finegold, M ;
Weissman, IL ;
Grompe, M .
NATURE MEDICINE, 2000, 6 (11) :1229-1234