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Establishment of a Novel Fetal Growth Restriction Model and Development of a Stem-Cell Therapy Using Umbilical Cord-Derived Mesenchymal Stromal Cells.
Frontiers in Cellular Neuroscience ( IF 5.3 ) Pub Date : 2020-06-16 , DOI: 10.3389/fncel.2020.00212
Yuma Kitase 1, 2 , Yoshiaki Sato 1 , Sakiko Arai 1, 2 , Atsuto Onoda 1, 3 , Kazuto Ueda 1 , Shoji Go 1 , Haruka Mimatsu 1, 2 , Mahboba Jabary 1, 2 , Toshihiko Suzuki 1 , Miharu Ito 1 , Akiko Saito 1 , Akihiro Hirakawa 4 , Takeo Mukai 5 , Tokiko Nagamura-Inoue 5 , Yoshiyuki Takahashi 2 , Masahiro Tsuji 6 , Masahiro Hayakawa 1
Affiliation  

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.



中文翻译:

新型胎儿生长受限模型的建立和脐带间充质基质细胞干细胞疗法的发展。

胎儿生长受限(FGR)是产前缺血/低氧暴露的主要并发症,影响5%-10%的怀孕。它会引起各种疾病,包括由于慢性缺氧,循环衰竭和营养不良引起的神经发育障碍。通过胎盘,目前尚无治疗方法。因此,开发治疗方法是当务之急。我们的目的是开发一种逐渐限制子宫/胎盘血流量的新型FGR大鼠模型,并评估给予脐带间充质基质细胞(UC-MSCs)的治疗效果。为了创建FGR大鼠模型,我们使用了在外壁上具有钛的类mer收缩器,该类收缩器由C形酪蛋白组成,其内部具有一个凹口和中心孔,吸水后逐渐变窄。在妊娠的第17天,将类动物收缩器附着在双侧卵巢/子宫动脉上,以诱发慢性轻度局部缺血,从而导致FGR,体重减轻20%以上。静脉给药后1×10 5对于UC-MSC,我们在出生后1周的负地轴测试和5个月大的轮式跑步机测试中证实了UC-​​MSC组的显着改善。在免疫生物学评估中,计数的神经元总数通过UC-MSC组的立体计数方法显着高于媒介物治疗组。这些结果表明,UC-MSC对FGR大鼠具有神经损伤的治疗作用。

更新日期:2020-07-28
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