RECONSTITUTION OF TRACHEAL GRAFTS WITH A GENETICALLY MODIFIED EPITHELIUM

被引:58
作者
ENGELHARDT, JF
ALLEN, ED
WILSON, JM
机构
[1] UNIV MICHIGAN,MED CTR,HOWARD HUGHES MED INST,DEPT INTERNAL MED,ANN ARBOR,MI 48109
[2] UNIV MICHIGAN,MED CTR,HOWARD HUGHES MED INST,DEPT BIOL CHEM,ANN ARBOR,MI 48109
关键词
CYSTIC FIBROSIS; GENE THERAPY; RECOMBINANT RETROVIRUSES;
D O I
10.1073/pnas.88.24.11192
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A rational approach to the development of gene therapies for cystic fibrosis requires a better understanding of the cellular targets for gene transfer in the airway epithelium. We have used recombinant retroviruses to study the dynamics and lineage relationships of a regenerating rat tracheal epithelium. Primary cultures of tracheal epithelial cells were exposed to lacZ-transducing retroviruses and subsequently seeded into denuded trachea that were implanted into BALB/c (nu/nu) mice. The grafts developed a fully differentiated mucociliary epithelium containing large clones of lacZ-expressing cells with virtually all cell types represented within each clone. These data are most consistent with gene transfer into a putative progenitor cell that is capable of extensive self renewal and pleuripotent development. Vector-specific variation in transgene expression was noted in the various cell types.
引用
收藏
页码:11192 / 11196
页数:5
相关论文
共 21 条
  • [1] GENERATION OF CAMP-ACTIVATED CHLORIDE CURRENTS BY EXPRESSION OF CFTR
    ANDERSON, MP
    RICH, DP
    GREGORY, RJ
    SMITH, AE
    WELSH, MJ
    [J]. SCIENCE, 1991, 251 (4994) : 679 - 682
  • [2] BEUER R, 1990, AM J RESPIR CELL MOL, V2, P51
  • [3] Boat T.F., 1989, METABOLIC BASIS INHE, P2649
  • [4] BOREN HG, 1978, PATHOGENESIS THERAPY, P369
  • [5] SAFE AND EFFICIENT GENERATION OF RECOMBINANT RETROVIRUSES WITH AMPHOTROPIC AND ECOTROPIC HOST RANGES
    DANOS, O
    MULLIGAN, RC
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (17) : 6460 - 6464
  • [6] TRACHEAL EPITHELIUM - CELL-KINETICS AND DIFFERENTIATION IN NORMAL RAT-TISSUE
    DONNELLY, GM
    HAACK, DG
    HEIRD, CS
    [J]. CELL AND TISSUE KINETICS, 1982, 15 (02): : 119 - 130
  • [7] CORRECTION OF THE CYSTIC-FIBROSIS DEFECT INVITRO BY RETROVIRUS-MEDIATED GENE-TRANSFER
    DRUMM, ML
    POPE, HA
    CLIFF, WH
    ROMMENS, JM
    MARVIN, SA
    TSUI, LC
    COLLINS, FS
    FRIZZELL, RA
    WILSON, JM
    [J]. CELL, 1990, 62 (06) : 1227 - 1233
  • [8] INAYAMA Y, 1988, LAB INVEST, V58, P706
  • [9] JEFFERY PK, 1975, J ANAT, V120, P295
  • [10] EPITHELIAL PROGENITOR CELLS IN THE RAT TRACHEA
    JOHNSON, NF
    HUBBS, AF
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1990, 3 (06) : 579 - 585