Extensive amplification and self-renewal of human primitive hematopoietic stem cells from cord blood

被引:389
作者
Piacibello, W
Sanavio, F
Garetto, L
Severino, A
Bergandi, D
Ferrario, J
Fagioli, F
Berger, M
Aglietta, M
机构
[1] UNIV TURIN,TORINO MED SCH,OSPED MAURIZIANO,I-10126 TURIN,ITALY
[2] INST CANC RES & TREATMENT,CANDIOLO,ITALY
[3] UNIV TURIN,DEPT PEDIAT,I-10124 TURIN,ITALY
关键词
D O I
10.1182/blood.V89.8.2644
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The use of umbilical cord blood as a source of marrow repopulating cells for the treatment of pediatric malignancies has been established. Given the general availability, the ease of procurement, and progenitor content, cord blood is an attractive alternative to bone marrow or growth factor mobilized peripheral blood cells as a source of transplantable hematopoietic tissue. However, there is a major potential limitation to the widespread use of card blood as a source of hematopoietic stem cells for marrow replacement and gene therapy. There may be enough hematopoietic stem cells to reconstitute children, but the ability to engraft an adult might require ex vivo manipulations, We describe an in vitro system in which the growth of cord blood CD34(+) cells is sustained and greatly expanded for more than 6 months by the simple combination of two hematopoietic growth factors. Progenitors and cells belonging to all hematopoietic lineages are continuously and increasingly generated (the number of colony-forming unit-granulocyte-macrophage [CFU-GM] present at the end of 6 months of culture are well over 2,000,000-foId the CFU-GM present at the beginning of the culture). Very primitive hematopoietic progenitors, including long-term culture-initiating cells (LTC-ICs) and blast cell colony-forming units, are also greatly expanded (after 20 weeks of liquid culture, LTC-IC number is over 200,000-foId the initial number). The extremely prolonged maintenance and the massive expansion of these progenitors, which share many similarities with murine long-term repopulating cells, suggest that extensive renewal and little differentiation take place. This system might prove useful in diverse clinical settings involving treatment of grown-up children and adults with transplantation of normal or genetically manipulated hematopoietic stem cells. (C) 1997 by The American Society of Hematology.
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页码:2644 / 2653
页数:10
相关论文
共 52 条
  • [1] AGLIETTA M, 1991, BLOOD, V77, P1191
  • [2] Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietin receptor c-mpl
    Alexander, WS
    Roberts, AW
    Nicola, NA
    Li, RL
    Metcalf, D
    [J]. BLOOD, 1996, 87 (06) : 2162 - 2170
  • [3] BARNETT MJ, 1989, BONE MARROW TRANSPL, V4, P345
  • [4] IDENTIFICATION AND CLONING OF A MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR THAT IS A LIGAND FOR THE CYTOKINE RECEPTOR MPL
    BARTLEY, TD
    BOGENBERGER, J
    HUNT, P
    LI, YS
    LU, HS
    MARTIN, F
    CHANG, MS
    SAMAL, B
    NICHOL, JL
    SWIFT, S
    JOHNSON, MJ
    HSU, RY
    PARKER, VP
    SUGGS, S
    SKRINE, JD
    MEREWETHER, LA
    CLOGSTON, C
    HSU, E
    HOKOM, MM
    HORNKOHL, A
    CHOI, E
    PANGELINAN, M
    SUN, Y
    MAR, V
    MCNINCH, J
    SIMONET, L
    JACOBSEN, F
    XIE, C
    SHUTTER, J
    CHUTE, H
    BASU, R
    SELANDER, L
    TROLLINGER, D
    SIEU, L
    PADILLA, D
    TRAIL, G
    ELLIOTT, G
    IZUMI, R
    COVEY, T
    CROUSE, J
    GARCIA, A
    XU, W
    DELCASTILLO, J
    BIRON, J
    COLE, S
    HU, MCT
    PACIFICI, R
    PONTING, I
    SARIS, C
    WEN, D
    [J]. CELL, 1994, 77 (07) : 1117 - 1124
  • [5] ISOLATION OF A CANDIDATE HUMAN HEMATOPOIETIC STEM-CELL POPULATION
    BAUM, CM
    WEISSMAN, IL
    TSUKAMOTO, AS
    BUCKLE, AM
    PEAULT, B
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (07) : 2804 - 2808
  • [6] FUNCTIONAL ISOLATION AND CHARACTERIZATION OF HUMAN HEMATOPOIETIC STEM-CELLS
    BERARDI, AC
    WANG, AL
    LEVINE, JD
    LOPEZ, P
    SCADDEN, DT
    [J]. SCIENCE, 1995, 267 (5194) : 104 - 108
  • [7] BERTONCELLO I, 1991, EXP HEMATOL, V19, P174
  • [8] BREEMS DA, 1994, LEUKEMIA, V8, P1095
  • [9] GROWTH-CHARACTERISTICS AND EXPANSION OF HUMAN UMBILICAL-CORD BLOOD AND ESTIMATION OF ITS POTENTIAL FOR TRANSPLANTATION IN ADULTS
    BROXMEYER, HE
    HANGOC, G
    COOPER, S
    RIBEIRO, RC
    GRAVES, V
    YODER, M
    WAGNER, J
    VADHANRAJ, S
    BENNINGER, L
    RUBINSTEIN, P
    BROUN, ER
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (09) : 4109 - 4113
  • [10] HUMAN UMBILICAL-CORD BLOOD - A CLINICALLY USEFUL SOURCE OF TRANSPLANTABLE HEMATOPOIETIC STEM PROGENITOR CELLS
    BROXMEYER, HE
    GLUCKMAN, E
    AUERBACH, A
    DOUGLAS, GW
    FRIEDMAN, H
    COOPER, S
    HANGOC, G
    KURTZBERG, J
    BARD, J
    BOYSE, EA
    [J]. INTERNATIONAL JOURNAL OF CELL CLONING, 1990, 8 : 76 - 91