Long-term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+ cells in patients with chronic

被引:100
作者
Leviar, N. [1 ]
Pai, M. [1 ]
Habib, N. A. [1 ]
Tait, P. [2 ]
Jiao, L. R. [1 ]
Marley, S. B. [3 ]
Davis, J. [3 ]
Dazzi, E. [3 ]
Smadja, C. [4 ]
Jensen, S. L. [1 ]
Nicholls, J. P. [1 ]
Apperley, J. E. [3 ]
Gordon, M. Y. [3 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Surg, London W12 0NN, England
[2] Hammersmith Hosp, Dept Radiol, NHS Trust, London, England
[3] Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London, England
[4] Hop Antoine Beclere, Paris, France
关键词
D O I
10.1111/j.1365-2184.2008.00491.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Evidence is growing in support of the role of stem cells as an attractive alternative in treatment of liver diseases. Recently, we have demonstrated the feasibility and safety of infusing CD34(+) adult stem cells; this was performed on five patients with chronic liver disease. Here, we present the results of long-term follow-up of these patients. Between 1 x 10(6) and 2 x 10(8) CD34(+) cells were isolated and injected into the portal vein or hepatic artery. The patients were monitored for side effects, toxicity and changes in clinical, haematological and biochemical parameters; they were followed up for 12-18 months. All patients tolerated the treatment protocol well without any complications or side effects related to the procedure, also there were no side effects noted on long-term follow-up. Four patients showed an initial improvement in serum bilirubin level, which was maintained for up to 6 months. There was marginal increase in serum bilirubin in three of the patients at 12 months, while the fourth patient's serum bilirubin increased only at 18 months post-infusion. Computed tomography scan and serum alpha-foetoprotein monitoring showed absence of focal lesions. The study indicated that the stem cell product used was safe in the short and over long term, by absence of tumour formation. The investigation also illustrated that the beneficial effect seemed to last for around 12 months. This trial shows that stem cell therapy may have potential as a possible future therapeutic protocol in liver regeneration.
引用
收藏
页码:115 / 125
页数:11
相关论文
共 24 条
[1]   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
[2]   Early gene expression of hepatocyte growth factor in mononuclear phagocytes of rat liver after administration of carbon tetrachloride [J].
Armbrust, T ;
Batusic, D ;
Xia, LQ ;
Ramadori, G .
LIVER, 2002, 22 (06) :486-494
[3]   Overexpression of Bcl-2 attenuates apoptosis and protects against myocardial I/R injury in transgenic mice [J].
Chen, ZY ;
Chua, CC ;
Ho, YS ;
Hamdy, RC ;
Chua, BHL .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2001, 280 (05) :H2313-H2320
[4]   Hematopoietic stem cell trafficking in liver injury [J].
Dalakas, E ;
Newsome, PN ;
Harrison, DJ ;
Plevris, JN .
FASEB JOURNAL, 2005, 19 (10) :1225-1231
[5]   Portal application of autologous CD133+ bone marrow cells to the liver:: A novel concept to support hepatic regeneration [J].
Esch, JSA ;
Knoefel, WT ;
Klein, M ;
Ghodsizad, A ;
Fuerst, G ;
Poll, LW ;
Piechaczek, C ;
Burchardt, ER ;
Feifel, N ;
Stoldt, V ;
Stockschläder, M ;
Stoecklein, N ;
Tustas, RY ;
Eisenberger, CF ;
Peiper, M ;
Häussinger, D ;
Hosch, SB .
STEM CELLS, 2005, 23 (04) :463-470
[6]   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
[7]  
Hatch Heather M., 2002, Cloning and Stem Cells, V4, P339, DOI 10.1089/153623002321025014
[8]   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
[9]   Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia [J].
Kawamoto, A ;
Tkebuchava, T ;
Yamaguchi, JI ;
Nishimura, H ;
Yoon, YS ;
Milliken, C ;
Uchida, S ;
Masuo, O ;
Iwaguro, H ;
Ma, H ;
Hanley, A ;
Silver, M ;
Kearney, M ;
Losordo, DW ;
Isner, JM ;
Asahara, T .
CIRCULATION, 2003, 107 (03) :461-468
[10]   HGF, SDF-1, and MMP-9 are involved in stress-induced human CD34+ stem cell recruitment to the liver [J].
Kollet, O ;
Shivtiel, S ;
Chen, YQ ;
Suriawinata, J ;
Thung, SN ;
Dabeva, MD ;
Kahn, J ;
Spiegel, A ;
Dar, A ;
Samira, S ;
Goichberg, P ;
Kalinkovich, A ;
Arenzana-Seisdedos, F ;
Nagler, A ;
Hardan, Z ;
Revel, M ;
Shafritz, DA ;
Lapidot, T .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (02) :160-169