Establishment of a Novel Fetal Growth Restriction Model and Development of a Stem-Cell Therapy Using Umbilical Cord-Derived Mesenchymal Stromal Cells

• Main Authors: Yuma Kitase, Yoshiaki Sato, Sakiko Arai, Atsuto Onoda, Kazuto Ueda, Shoji Go, Haruka Mimatsu, Mahboba Jabary, Toshihiko Suzuki, Miharu Ito, Akiko Saito, Akihiro Hirakawa, Takeo Mukai, Tokiko Nagamura-Inoue, Yoshiyuki Takahashi, Masahiro Tsuji, Masahiro Hayakawa
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-07-01
• Series: Frontiers in Cellular Neuroscience
• Subjects: umbilical cord-derived mesenchymal stromal cells; fetal growth restriction; mesenchymal stem cell; neurodevelopment; stem cells
• Online Access: https://www.frontiersin.org/article/10.3389/fncel.2020.00212/full

Fetal growth restriction (FGR) is a major complication of prenatal ischemic/hypoxic exposure and affects 5%–10% of pregnancies. It causes various disorders, including neurodevelopmental disabilities due to chronic hypoxia, circulatory failure, and malnutrition via the placenta, and there is no established treatment. Therefore, the development of treatments is an urgent task. We aimed to develop a new FGR rat model with a gradual restrictive load of uterus/placental blood flow and to evaluate the treatment effect of the administration of umbilical cord-derived mesenchymal stromal cells (UC-MSCs). To create the FGR rat model, we used ameroid constrictors that had titanium on the outer wall and were composed of C-shaped casein with a notch and center hole inside that gradually narrowed upon absorbing water. The ameroid constrictors were attached to bilateral ovarian/uterine arteries on the 17th day of pregnancy to induce chronic mild ischemia, which led to FGR with over 20% bodyweight reduction. After the intravenous administration of 1 × 105 UC-MSCs, we confirmed a significant improvement in the UC-MSC group in a negative geotaxis test at 1 week after birth and a rotarod treadmill test at 5 months old. In the immunobiological evaluation, the total number of neurons counted via the stereological counting method was significantly higher in the UC-MSC group than in the vehicle-treated group. These results indicate that the UC-MSCs exerted a treatment effect for neurological impairment in the FGR rats.