Zhang Dan, Fu Lihua, Wang Leilei, Lin Lin, Yu Lihong, Zhang Lijun, Shang Tao
a Department of Obstetrics and Gynaecology , Shenyang Women's and Children's Hospital , Shenyang , China.
b Department of Obstetrics and Gynaecology , Ditan Hospital Capital Medical University , Beijing , China.
Hypertens Pregnancy. 2017 Aug;36(3):247-258. doi: 10.1080/10641955.2017.1329429. Epub 2017 Jun 13.
Immunomodulation by mesenchymal stem cells (MSCs) is potentially important for maintaining peripheral tolerance. Preeclampsia may be due to maternal immune rejection of the genetically foreign fetus. This study aimed to investigate the biological function of human umbilical cord-derived mesenchymal stem cells (HU-MSCs) for the treatment of angiotensin receptor agonistic autoantibody (AT1-AA)-induced hypertension during pregnancy. HU-MSCs were isolated, cultured, and labeled in vitro. AT1-AA and HU-MSCs were administered to pregnant rats. Green fluorescent protein (GFP)-positive HU-MSCs infused in vivo were identified by immunofluorescence. Systolic blood pressure (SBP) was evaluated. The effects of HU-MSCs on fetal weight, kidney burden, and spiral artery remodeling, as well as on the expression of tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), and heme oxygenase 1 (HO-1), were investigated. The SBP levels in the HU-MSC-treated pregnant hypertension rats decreased by gestational day 19. The reduction in fetal weight was largely ameliorated after HU-MSC treatment. Lesion burden in the kidney was attenuated and spiral artery remodeling was improved in HU-MSC-treated pregnant hypertension rats. However, green fluorescent protein (GFP)-labeled cells were sparingly observed in the kidney and placenta. Intravenous infusion of HU-MSCs into AT1-AA-induced rats significantly downregulated serum TNF-α levels and upregulated IL-10 levels, concomitant with increased placenta and mesometrial triangle (MT) HO-1 expression. Taken together, intravenous infusion of HU-MSCs ameliorates AT1-AA-induced pregnancy hypertension, intrauterine growth retardation, kidney impairment, and spiral artery remodeling impairment. Moreover, the potential benefits of HU-MSCs may be attributable to both an interference with the pathogenic immune response and a paracrine cytoprotective action.
间充质干细胞(MSCs)的免疫调节作用对于维持外周免疫耐受可能具有重要意义。子痫前期可能是由于母体对基因上异己的胎儿产生免疫排斥反应所致。本研究旨在探讨人脐带间充质干细胞(HU-MSCs)在治疗妊娠期间血管紧张素受体激动性自身抗体(AT1-AA)诱导的高血压中的生物学功能。HU-MSCs在体外进行分离、培养和标记。将AT1-AA和HU-MSCs给予妊娠大鼠。通过免疫荧光鉴定体内注入的绿色荧光蛋白(GFP)阳性HU-MSCs。评估收缩压(SBP)。研究了HU-MSCs对胎儿体重、肾脏负担、螺旋动脉重塑以及肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)和血红素加氧酶1(HO-1)表达的影响。在妊娠第19天时,经HU-MSC治疗的妊娠高血压大鼠的SBP水平降低。HU-MSC治疗后,胎儿体重减轻的情况在很大程度上得到改善。经HU-MSC治疗的妊娠高血压大鼠的肾脏病变负担减轻,螺旋动脉重塑得到改善。然而,在肾脏和胎盘中很少观察到绿色荧光蛋白(GFP)标记的细胞。向AT1-AA诱导的大鼠静脉输注HU-MSCs可显著下调血清TNF-α水平并上调IL-10水平,同时胎盘和子宫系膜三角(MT)中HO-1的表达增加。综上所述,静脉输注HU-MSCs可改善AT1-AA诱导的妊娠高血压、宫内生长受限、肾脏损害和螺旋动脉重塑损害。此外,HU-MSCs的潜在益处可能归因于对致病性免疫反应的干扰和旁分泌细胞保护作用。
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