Human cord blood progenitors sustain thymic T-cell development and a novel form of angiogenesis

被引:46
作者
Crisa, L
Cirulli, V
Smith, KA
Ellisman, MH
Torbett, BE
Salomon, DR
机构
[1] Scripps Res Inst, Dept Mol & Expt Med, MEM55, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[3] Univ Calif San Diego, Whittier Inst, Dept Pediat, San Diego, CA 92103 USA
[4] Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, San Diego, CA 92103 USA
关键词
D O I
10.1182/blood.V94.11.3928.423k02_3928_3940
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
There is growing interest in using human umbilical cord blood (CB) for allogeneic bone marrow transplantation (BMT), particularly in children. Thus, CB has been identified as a rich source of hematopoietic progenitors of the erythroid, myeloid, and B-cell lineages. Whether CB blood cells engrafting in the BM space also comprise T-cell progenitors capable of trafficking to the thymus and reconstituting a functional thymopoiesis in young recipients is presently unknown, Here, we show that CB progenitors, engrafted in the BM of immunodeficient mice, sustain human thymopoiesis by generating circulating T-cell progenitors capable of homing to and developing within a human thymic graft. Surprisingly, development of CB stem cells in this in vivo model extended to elements of the endothelial cell lineage, which contributed to the revascularization of transplants and wound healing. These results demonstrate that human CB stem cell transplantation can reconstitute thymic-dependent T-cell lymphopoiesis and show a novel role of CB-derived hematopoietic stem cells in angiogenesis. (C) 1999 by The American Society of Hematology.
引用
收藏
页码:3928 / 3940
页数:13
相关论文
共 56 条
[51]  
Wagner JE, 1996, BLOOD, V88, P795
[52]   Purified hematopoietic stem cells without facilitating cells can repopulate fully allogeneic recipients across entire major histocompatibility complex transplantation barrier in mice [J].
Wang, BY ;
El-Badri, NS ;
Cherry ;
Good, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (26) :14632-14636
[53]  
Wood HB, 1997, BLOOD, V90, P2300
[54]   HUMAN BONE-MARROW AND UMBILICAL-CORD BLOOD-CELLS GENERATE CD4+ AND CD8+ SINGLE-POSITIVE T-CELLS IN MURINE FETAL THYMUS ORGAN-CULTURE [J].
YEOMAN, H ;
GRESS, RE ;
BARE, CV ;
LEARY, AG ;
BOYSE, EA ;
BARD, J ;
SHULTZ, LD ;
HARRIS, DT ;
DELUCA, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (22) :10778-10782
[55]   Severe combined immunodeficiency mice engrafted with human T cells, B cells, and myeloid cells after transplantation with human fetal bone marrow or liver cells and implanted with human fetal thymus: A model for studying human gene therapy [J].
Yurasov, S ;
Kollmann, TR ;
Kim, A ;
Raker, CA ;
Hachamovitch, M ;
WongStaal, F ;
Goldstein, H .
BLOOD, 1997, 89 (05) :1800-1810
[56]  
Zhong RK, 1996, J IMMUNOL, V157, P138