Bi-directional Cell Trafficking Between Mother and Fetus in Mouse Placenta

Vernochet, Cécile; Caucheteux, Stéphane; Kanellopoulos-Langevin, Colette

doi:10.1016/j.placenta.2006.10.006

Cited by 53 publications

(59 citation statements)

References 32 publications

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“…This timing of fetal cell trafficking is similar to that reported by Vernochet and colleagues [15], in which the number of fetal 2 e10 -9 0 0 0 0 0 0 0 0 0 3 e10 3 8 0 0 0 0 0 0 0 0 0 4 e11 4 8 0 0 0 0 0 0 0 0 0 5 e11 5 10 0 0 0 0 0 0 0 0 0 6 e12 3 6 0 25 0 0 0 414 19 0 0 7 e13 2 Dashes indicate where the number of transgenic pups is unknown, but at least 1 pup was GFP positive. z Dash indicates where the total number of pups is unknown (due to death of litter).…”

Section: Fetal Cell Microchimerism Is Maximal Near Termsupporting

confidence: 90%

“…Prior animal studies have, in general, limited their focus to a specific organ or time point during pregnancy. In a histologic study of murine placental implantation sites harvested between Days 6 and 19 postcoitum, Vernochet and colleagues [15] demonstrated, using fetomaternal genetic differences, that fetal cells first entered the maternal blood at Embryonic Days 10-12. Fetal cells then entered the maternal decidua in increased amounts as gestation progressed.…”

Section: Introductionmentioning

confidence: 99%

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Fetomaternal Trafficking in the Mouse Increases as Delivery Approaches and Is Highest in the Maternal Lung1

Fujiki

Johnson

Tighiouart

et al. 2008

Biology of Reproduction

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The purpose of the study was to understand in more detail the natural history of fetomaternal cell trafficking in healthy pregnant mice. Our goal was to identify the best target organs and days during pregnancy for further mechanistic studies of the role of fetal cells in maternal disease and injury. C57BL/6J wild-type virgin females (n = 54) were mated with congenic enhanced green fluorescent protein (EGFP) transgenic males. During pregnancy and after delivery, female mice were euthanized, and eight organs and blood were analyzed for the presence of fetal GFP+ cells with flow cytometry and real-time quantitative PCR. Maternal lungs, liver, and spleen were also analyzed by fluorescent stereomicroscopy. Fetal GFP+ cells were first found at low frequency at Embryonic Day 11, increased to a maximum at Embryonic Day 19, and decreased rapidly postpartum. These fetal cell dynamics were significantly reproducible among all mice studied. In addition, there was a consistent distribution of fetal cells within maternal organs, with lung, liver, blood, and spleen having the greatest concentrations; these were highly correlated at all time points (P < 0.0001). Maternal lung contained 10- to 100-fold more fetal cells than any other organ, and using all three techniques, the number of fetal cells detected was the most consistent and reproducible in this organ. Stereomicroscopy showed that within the lung, fetal cells were widely and apparently randomly distributed. Using a murine model, our data demonstrate that fetomaternal cellular trafficking occurs in reproducible patterns, is maximal near term delivery, and has predilection for the maternal lung.

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Section: Fetal Cell Microchimerism Is Maximal Near Termsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Fetomaternal Trafficking in the Mouse Increases as Delivery Approaches and Is Highest in the Maternal Lung1

Fujiki

Johnson

Tighiouart

et al. 2008

Biology of Reproduction

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“…In humans, maternal-fetal cellular trafficking may contribute to fetal immune development and maternal-fetal tolerance, inducing the fetus to develop Tregs against maternal antigens (19). Changes in the levels of maternal-fetal cellular trafficking have been reported to correspond with maternal-fetal histocompatibility in the mouse model, suggesting that cellular trafficking has implications for maternal-fetal tolerance (37,40).…”

Section: Discussionmentioning

confidence: 99%

Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice

Nijagal¹,

Wegorzewska²,

Jarvis³

et al. 2011

J. Clin. Invest.

126

133

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Transplantation of allogeneic stem cells into the early gestational fetus, a treatment termed in utero hematopoietic cell transplantation (IUHCTx), could potentially overcome the limitations of bone marrow transplants, including graft rejection and the chronic immunosuppression required to prevent rejection. However, clinical use of IUHCTx has been hampered by poor engraftment, possibly due to a host immune response against the graft. Since the fetal immune system is relatively immature, we hypothesized that maternal cells trafficking into the fetus may pose the true barrier to effective IUHCTx. Here, we have demonstrated that there is macrochimerism of maternal leukocytes in the blood of unmanipulated mouse fetuses, with substantial increases in T cell trafficking after IUHCTx. To determine the contribution of these maternal lymphocytes to rejection after IUHCTx, we bred T and/or B cell-deficient mothers to wild-type fathers and performed allogeneic IUHCTx into the immunocompetent fetuses. There was a marked improvement in engraftment if the mother lacked T cells but not B cells, indicating that maternal T cells are the main barrier to engraftment. Furthermore, when the graft was matched to the mother, there was no difference in engraftment between syngeneic and allogeneic fetal recipients. Our study suggests that the clinical success of IUHCTx may be improved by transplanting cells matched to the mother.

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“…In contrast to our transplantation experiments using pure EGFP+ donor MSC, analyses of "simple" mouse crossings suggest that the passage of fetal cells to the decidua begins with E10 and increases steadily. However, from their morphology it appears that these cells are rather of trophoblastic giant cell origin, than being fetal stem cells [ 24 ]. Our observation that E12 transplantation leads to a higher probability of microchimerism in maternal bone marrow could be explained by gestational age-dependent differences at the fetomaternal interface with regard to the changing expression pattern of homingassociated molecules between E12 and E14, which might be relevant not only for lymphocytes, but also for MSC [ 43 ].…”

Section: Author Disclosure Statementmentioning

confidence: 70%

“…The number of cases with allogeneic IUT in our series is low, but clearly shows that there is no persistent microchimerism after allogeneic IUT. In contrast, allogeneic crosses resulted in persistent fetal cells in maternal blood until 3 weeks after delivery [ 24 ].…”

Section: Author Disclosure Statementmentioning

confidence: 96%

Transplacental Traffic After In Utero Mesenchymal Stem Cell Transplantation

Troeger

Perahud

Moser

et al. 2010

Stem Cells and Development

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Transplacental traffic of fetal progenitor and differentiated cells is a well-known phenomenon in pregnancies. We hypothesize that intrauterine stem cell transplantation leads to microchimerism in the dams and that this is gestational age-dependent. EGFP+ fetal liver-derived mesenchymal stem cell (MSC) (10(5) per fetus) were injected intraperitoneally into congeneic and allogeneic recipient fetuses at E12 versus E13.5 of murine pregnancy (56 dams). Engraftment in maternal organs was evaluated using TaqMan quantitative polymerase chain reaction (PCR) and fluorescence microscopy during pregnancy (1, 3, and 7 days after in utero transplantation [IUT]) and after delivery (1 and 4 weeks after delivery). One day after IUT donor cells were mainly found in the placenta (E12: 9/10 dams vs. E13.5: 4/8 dams) and laparotomy site (E12: 5/10 dams vs. E13.5: 4/8 dams). Three days after IUT these probabilities decreased significantly in the placenta to 3/8 and 1/3, respectively, whereas it was increased within the surgical wound to 8/8 and 2/4. One week after IUT donor cells could be detected in other single maternal organs, such as bone marrow or spleen. The surgical wound was chimeric in all dams. One week after delivery the surgical wound was still a major site of engraftment in both groups. E12 IUT resulted in detectable donor cell microchimerism in the maternal bone marrow (3/4), liver (2/4), lungs (1/4), spleen (1/4), and thymus (1/4), whereas engraftment probabilities were lower following E13.5 IUT (BM: 1/4, liver: 2/4, lungs: 1/4, spleen: 1/4, thymus: 0/4). At 4 weeks after delivery persistent microchimerism was found only after E12 IUT in various maternal organs (BM: 1/4, spleen: 1/4, lungs: 1/4) and within newly created surgical wounds (3/4), but completely not in the E13.5 group. Allogeneic IUT did also not result in any detectable long-term fetal microchimerism. An earlier IUT might lead to a higher transplacental traffic of donor MSC and persistent microchimerism within maternal tissues. Even 4 weeks after delivery, these cells are present in surgical wounds.

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Bi-directional Cell Trafficking Between Mother and Fetus in Mouse Placenta

Cited by 53 publications

References 32 publications

Fetomaternal Trafficking in the Mouse Increases as Delivery Approaches and Is Highest in the Maternal Lung1

Fetomaternal Trafficking in the Mouse Increases as Delivery Approaches and Is Highest in the Maternal Lung1

Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice

Transplacental Traffic After In Utero Mesenchymal Stem Cell Transplantation

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