Native amniotic fluid mesenchymal stem cell response in a model of fetal growth restriction

IF 3.2 3区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotherapy Pub Date : 2026-04-01 Epub Date: 2025-12-27 DOI:10.1016/j.jcyt.2025.102039

Abbie E. Naus , Kamila Moskowitzova , Ashlyn E. Whitlock , Ina Kycia , Tanya T. Dang , Shuqi B. Lin , Ranjan Maskey , David Zurakowski , Ronald Mathieu , Dario O. Fauza

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引用次数: 0

Abstract

Purpose

We sought to determine the impact of fetal growth restriction (FGR) on the cellularity of the amniotic fluid, with a focus on its mesenchymal stem cell (MSC) population.

Methods

Four time-dated pregnant Sprague-Dawley dams were exposed to alternating 12-h hypoxia (10.5% O2) cycles from gestational day 15 (E15) until term (E21; FGR group). Three time-dated pregnant Sprague-Dawley dams not exposed to hypoxia served as normal controls. At term, fresh amniotic fluid samples from all their fetuses (n = 88, equally divided between the two groups) underwent quantitative multicolor flow cytometry for the detection of live cells as well as of cells concomitantly expressing CD29, and CD44 (both are markers of MSCs), while being also negative for DAPI and CD45, utilizing standard gating strategies. Statistical analysis was by Wilcoxon rank-sum tests and median regression (P < 0.05).

Results

Placental efficiency was significantly lower in the FGR group compared to controls (P < 0.001), confirming reproduction of the disease model. There was no significant difference in the median individual amniotic fluid volume between the groups (P = 0.792). Compared to controls, FGR fetuses had statistically significantly lower densities of both total live cells as well as of live MSCs in the amniotic fluid (both P < 0.001). There was a significant decrease in the total number of MSCs in the FGR group versus controls (P < 0.001).

Conclusions

Native amniotic fluid MSC may be consumed in the setting of FGR. This provides further biological basis for transamniotic stem cell therapy as a potential novel treatment for this disease.

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胎儿生长受限模型中的天然羊水间充质干细胞反应

目的：我们试图确定胎儿生长受限（FGR）对羊水细胞的影响，重点关注其间充质干细胞（MSC）群体。方法选取4只妊娠期Sprague-Dawley母鼠，从妊娠第15天（E15）至足月（E21； FGR组）交替缺氧12 h （10.5% O2）。三个未暴露于缺氧环境的怀孕的Sprague-Dawley水坝作为正常对照。足月时，所有胎儿的新鲜羊水样本（n = 88，平均分为两组）采用定量多色流式细胞术检测活细胞以及同时表达CD29和CD44的细胞（两者都是MSCs的标记物），同时使用标准门控策略检测DAPI和CD45的阴性。统计学分析采用Wilcoxon秩和检验和中位数回归（P < 0.05）。结果与对照组相比，FGR组胎盘效率显著降低（P < 0.001），证实了疾病模型的再现。两组间羊水中位数差异无统计学意义（P = 0.792）。与对照组相比，FGR胎儿羊水中总活细胞和活间充质干细胞的密度在统计学上显著降低（P < 0.001）。与对照组相比，FGR组的MSCs总数显著减少（P < 0.001）。结论在FGR的情况下，羊水间充质干细胞可能被消耗。这为羊膜干细胞治疗作为一种潜在的新型治疗方法提供了进一步的生物学基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytotherapy 医学-生物工程与应用微生物

CiteScore

6.30

自引率

4.40%

发文量

683

审稿时长

49 days

期刊介绍： The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.