Identification of fetal mesenchymal stem cells in maternal blood: implications for non-invasive prenatal diagnosis

被引:97
作者
O'Donoghue, K
Choolani, M
Chan, J
de la Fuente, J
Kumar, S
Campagnoli, C
Bennett, PR
Roberts, IAG
Fisk, NM
机构
[1] Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, Div Paediat Obstet & Gynaecol, London W12 0NN, England
[2] Univ London Imperial Coll Sci Technol & Med, Dept Haematol, Div Invest Sci, London W12 0NN, England
关键词
fetal cells; maternal blood; mesenchymal stem cells; microchimerism; non-invasive prenatal diagnosis;
D O I
10.1093/molehr/gag063
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Strategies for genetic prenatal diagnosis on fetal cells in the maternal circulation have been limited by lack of a cell type present only in fetal blood. However, the recent identification of mesenchymal stem cells (MSC) in first trimester fetal blood offers the prospect of targeting MSC for non-invasive prenatal diagnosis. We developed protocols for fetal MSC enrichment from maternal blood and determined sensitivity and specificity in mixing experiments of male fetal MSC added to female blood, in dilutions from 1 in 10(5) to 10(8). We then used the optimal protocol to isolate fetal MSC from maternal blood in the first trimester, using blood taken after surgical termination of pregnancy as a model of increased feto-maternal haemorrhage. In model mixtures, we could amplify one male fetal MSC in 2.5x10(7) adult female nucleated cells, yielding a 100% pure population of fetal cells, but not one fetal MSC in 10(8) nucleated cells. Fetal MSC were identified in one of 20 post-termination maternal blood samples and confirmed as fetal MSC by XY fluorescence in-situ hybridization (FISH), immunophenotyping and osteogenic and adipogenic differentiation. We report the isolation of fetal MSC from maternal blood; however, their rarity in post-termination blood suggests they are unlikely to have a role in non-invasive prenatal diagnosis. Failure to locate these cells routinely may be attributed to their low frequency in maternal blood, to sensitivity limitations of enrichment technology, and/or to their engraftment in maternal tissues soon after transplacental passage. We speculate that gender microchimerism in post-reproductive maternal tissues might result from feto-maternal trafficking of MSC in early pregnancy.
引用
收藏
页码:497 / 502
页数:6
相关论文
共 47 条
  • [1] Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis
    Artlett, CM
    Smith, JB
    Jimenez, SA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1998, 338 (17) : 1186 - 1191
  • [2] The monoclonal antibody SH-2, raised against human mesenchymal stem cells, recognizes an epitope on endoglin (CD105)
    Barry, FP
    Boynton, RE
    Haynesworth, S
    Murphy, JM
    Zaia, J
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 265 (01) : 134 - 139
  • [3] Significant fetal-maternal hemorrhage after termination of pregnancy: Implications for development of fetal cell microchimerism
    Bianchi, DW
    Farina, A
    Weber, W
    Delli-Bovi, LC
    DeRiso, M
    Williams, JM
    Klinger, KW
    [J]. AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2001, 184 (04) : 703 - 706
  • [4] Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum
    Bianchi, DW
    Zickwolf, GK
    Weil, GJ
    Sylvester, S
    DeMaria, MA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (02) : 705 - 708
  • [5] CLINICAL-TRIALS AND EXPERIENCE - BOSTON
    BIANCHI, DW
    [J]. FETAL CELLS IN MATERNAL BLOOD: PROSPECTS FOR NONINVASIVE PRENATAL DIAGNOSIS, 1994, 731 : 92 - 102
  • [6] Bianchi DW, 1996, PRENATAL DIAG, V16, P289, DOI 10.1002/(SICI)1097-0223(199604)16:4<289::AID-PD843>3.3.CO
  • [7] 2-K
  • [8] Fetal cells in the maternal circulation: Feasibility for prenatal diagnosis
    Bianchi, DW
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 1999, 105 (03) : 574 - 583
  • [9] Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data
    Bianchi, DW
    Simpson, JL
    Jackson, LG
    Elias, S
    Holzgreve, W
    Evans, MI
    Dukes, KA
    Sullivan, LM
    Klinger, KW
    Bischoff, FZ
    Hahn, S
    Johnson, KL
    Lewis, D
    Wapner, RJ
    [J]. PRENATAL DIAGNOSIS, 2002, 22 (07) : 609 - 615
  • [10] PCR quantitation of fetal cells in maternal blood in normal and aneuploid pregnancies
    Bianchi, DW
    Williams, JM
    Sullivan, LM
    Hanson, FW
    Klinger, KW
    Shuber, AP
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (04) : 822 - 829