Male Cell Microchimerism in Normal and Diseased Female Livers From Fetal Life to Adulthood *

Guettier, Catherine; Sebagh, Mylène; Buard, Jérǒme; Feneux, D.; Ortin-Serrano, Monique; Gigou, M; Tricottet, V.; Reynès, M; Samuel, Didier; Féray, Cyrille

doi:10.1002/hep.20761

Cited by 66 publications

(51 citation statements)

References 36 publications

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“…Our results add to a strain of previous findings suggesting that during pregnancy, women acquire a population of multipotent stem cells able to adopt various phenotypes in maternal injured tissues (26). Fetal-derived cells can adopt epithelial, hepatocytic, hemopoietic, cardiomyocytic phenotypes in human studies (27)(28)(29)(30). Murine models have also clearly shown the capacity of fetal cells acquired during pregnancy to home to damaged maternal tissues and to acquire different phenotypes, such as hepatocytes, kidney tubular cells, or various CNS phenotypes (31)(32)(33).…”

Section: Discussionsupporting

confidence: 73%

Pregnancy Allows the Transfer and Differentiation of Fetal Lymphoid Progenitors into Functional T and B Cells in Mothers

Khosrotehrani

Leduc

Bachy

et al. 2008

The Journal of Immunology

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T lymphocytes of fetal origin found in maternal circulation after gestation have been reported as a possible cause for autoimmune diseases. During gestation, mothers acquire CD34+CD38+ cells of fetal origin that persist decades. In this study, we asked whether fetal T and B cells could develop from these progenitors in the maternal thymus and bone marrow during and after gestation. RAG−/−-deficient female mice (Ly5.2) were mated to congenic wild-type Ly5.1 mice (RAG+/+). Fetal double-positive T cells (CD4+CD8+) with characteristic TCR and IL-7R expression patterns could be recovered in maternal thymus during the resulting pregnancies. We made similar observations in the thymus of immunocompetent mothers. Such phenomenon was observed overall in 12 of 68 tested mice compared with 0 of 51 controls (p = 0.001). T cells could also be found in maternal spleen and produced IFN-γ in the presence of an allogenic or an Ag-specific stimulus. Similarly, CD19+IgM+ fetal B cells as well as plasma Igs could be found in maternal RAG−/− bone marrow and spleen after similar matings. Our results suggest that during gestation mothers acquire fetal lymphoid progenitors that develop into functional T cells. This fetal cell microchimerism may have a direct impact on maternal health.

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Section: Discussionsupporting

confidence: 73%

Pregnancy Allows the Transfer and Differentiation of Fetal Lymphoid Progenitors into Functional T and B Cells in Mothers

Khosrotehrani

Leduc

Bachy

et al. 2008

The Journal of Immunology

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“…In studies of women with various diseases and a prior pregnancy, fetal cells with various phenotypes have been found. The microchimeric cells express markers of epithelia, hepatocytes, leukocytes, or cardiomyocytes (13,21,28). Similar results have been found in mouse models of fetal cell microchimerism where fetal-derived cells can express markers of neurons, glial cells (27), hepatocytes, or renal tubular epithelium (29).…”

Section: Discussionsupporting

confidence: 68%

Maternal neoangiogenesis during pregnancy partly derives from fetal endothelial progenitor cells

Huu

Oster

Uzan

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Fetal progenitor cells enter the maternal circulation during pregnancy and can persist for decades. We aimed to determine the role of these cells in tissue inflammation during pregnancy. WT female mice were mated to males transgenic for the EGFP (ubiquitous) or the luciferase gene controlled by the VEGF receptor 2 (VEGFR2; V-Luc) promoter. A contact hypersensitivity reaction was triggered during such pregnancies. Fetal cells were tracked by using real-time quantitative amplification of the transgene (real-time PCR), Y chromosome in situ hybridization (FISH), immunofluorescence or in vivo bioluminescence imaging. Real-time PCR disclosed fetal cells in the inflamed areas in all tested mice (17/17) with higher frequency and numbers in the inflamed compared with the control areas (P ‫؍‬ 0.01). Double labeling demonstrated CD31؉ EGFP؉ fetal cells organized as blood vessels. In WT pregnant mice bearing V-Luc fetuses, a specific luciferase activity signal could be detected at the hypersensitivity site only, demonstrating the elective presence of VEGFR2-expressing fetal cells. In conclusion, using various techniques, we found the presence of fetal endothelial cells lining blood vessels in maternal sites of inflammation. These results imply that fetal endothelial progenitor cells are acquired by the mother and participate in maternal angiogenesis during pregnancy.angiogenesis ͉ chimerism ͉ gestation ͉ fetal stem cells

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“…6,8 In addition, several studies in women as well as in mice have previously demonstrated the specific detection of fetal microchimeric cells in different types of tissue damage seen in various maternal tissues such as heart, liver, intestine, kidney, and even brain. 12,[21][22][23][24] Of note, fetal-derived lymphoid progenitors acquired during gestation are even able to rescue immunodeficient mothers by developing into mature functional T and B lymphocytes in maternal thymus and bone marrow, respectively. 13 In maternal damaged organs, fetal cells have been shown to adopt the phenotype of the tissue itself and/or an endothelial phenotype.…”

Section: Discussionmentioning

confidence: 99%

Fetal Microchimeric Cells Participate in Tumour Angiogenesis in Melanomas Occurring during Pregnancy

Huu

Oster

Avril

et al. 2009

The American Journal of Pathology

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Melanoma is a major malignancy in younger individuals that accounts for 8% of all neoplasias associated with gestation. During pregnancy, a small number of fetal cells enter the maternal circulation. These cells persist and then migrate to various maternal tissues where they may engraft and differentiate, particularly if there is organ damage, adopting the phenotype of the host organ. To understand the relationship between melanoma and pregnancy, we analyzed these tumors in both humans and mice. Fetal cells were detected in 63% of human primary melanomas versus 12% in nevi during pregnancy (P ‫؍‬ 0.034) and in 57% of B16 melanomas in pregnant mice but never in normal skin (P ‫؍‬ 0.000022). More than 50% of these fetal cells expressed the CD34, CD31, or von Willebrand factor endothelial cell markers. In addition, the Lyve-1 lymphatic antigen was expressed by more than 30% of fetal cells in mice. In conclusion, we show that melanomas during pregnancy frequently harbor fetal cells that have an endothelial phenotype. Further studies are needed to assess whether the fetal contribution to lymphangiogenesis may alter the prognosis of the maternal tumor. (Am

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Male Cell Microchimerism in Normal and Diseased Female Livers From Fetal Life to Adulthood *

Cited by 66 publications

References 36 publications

Pregnancy Allows the Transfer and Differentiation of Fetal Lymphoid Progenitors into Functional T and B Cells in Mothers

Pregnancy Allows the Transfer and Differentiation of Fetal Lymphoid Progenitors into Functional T and B Cells in Mothers

Maternal neoangiogenesis during pregnancy partly derives from fetal endothelial progenitor cells

Fetal Microchimeric Cells Participate in Tumour Angiogenesis in Melanomas Occurring during Pregnancy

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