Transplacental Traffic After In Utero Mesenchymal Stem Cell Transplantation

Abstract

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.