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

被引：7

作者：

Kitase, Yuma ^{[1
,2
]}

Sato, Yoshiaki ^{[1
]}

Arai, Sakiko ^{[1
,2
]}

Onoda, Atsuto ^{[1
,3
]}

Ueda, Kazuto ^{[1
]}

Go, Shoji ^{[1
]}

Mimatsu, Haruka ^{[1
,2
]}

Jabary, Mahboba ^{[1
,2
]}

Suzuki, Toshihiko ^{[1
]}

Ito, Miharu ^{[1
]}

Saito, Akiko ^{[1
]}

Hirakawa, Akihiro ^{[4
]}

Mukai, Takeo ^{[5
]}

Nagamura-Inoue, Tokiko ^{[5
]}

Takahashi, Yoshiyuki ^{[2
]}

Tsuji, Masahiro ^{[6
]}

Hayakawa, Masahiro ^{[1
]}

机构：

[1] Nagoya Univ Hosp, Ctr Maternal Neonatal Care, Div Neonatol, Nagoya, Aichi, Japan

[2] Nagoya Univ, Dept Pediat, Grad Sch Med, Nagoya, Aichi, Japan

[3] Sanyo Onoda City Univ, Fac Pharmaceut Sci, Yamaguchi, Japan

[4] Med & Dent Univ, Div Biostat & Data Sci, Clin Res Ctr, Tokyo, Japan

[5] Univ Tokyo, Inst Med Sci, Dept Cell Proc & Transfus, Tokyo, Japan

[6] Kyoto Womens Univ, Fac Home Econ, Dept Food & Nutr, Kyoto, Japan

来源：

FRONTIERS IN CELLULAR NEUROSCIENCE | 2020年 / 14卷

基金：

日本学术振兴会;

关键词：

umbilical cord-derived mesenchymal stromal cells; fetal growth restriction; mesenchymal stem cell; neurodevelopment; stem cells; FOR-GESTATIONAL-AGE; CENTRAL-NERVOUS-SYSTEM; NEUROTROPHIC FACTOR; BONE-MARROW; INTRAUTERINE; BORN; RETARDATION; BDNF; EXPRESSION; ISCHEMIA;

D O I：

10.3389/fncel.2020.00212

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 malnutritionviathe 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 x 10(5)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 countedviathe 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.

引用

页数：13

共 81 条

[11] BDNF and TrkB protein expression is altered in the fetal hippocampus but not cerebellum after chronic prenatal compromise [J].