Cytotherapy · 2025
Native amniotic fluid mesenchymal stem cell response in a model of fetal growth restriction.
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Naus Abbie E, Moskowitzova Kamila, Whitlock Ashlyn E, Kycia Ina, Dang Tanya T, Lin Shuqi B, Maskey Ranjan, Zurakowski David, Mathieu Ronald, Fauza Dario O
Аннотация
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.
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.