Endothelial Progenitor Cells of the Human Placenta and Fetoplacental Circulation: A Potential Link to Fetal, Neonatal, and Long-term Health

Gumina, Diane L.; Su, Emily J.

doi:10.3389/fped.2017.00041

Cited by 16 publications

(11 citation statements)

References 39 publications

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“…PE contributes to perinatal and maternal morbidity and mortality and persists as a major obstetric concern;1–3,12 it is also a neonatal risk10 and a future risk for both mother and newborn 3,6–9,11. Advances in some molecular alterations related to the VEGF family in PE30 currently have clinical applications,25 including as predictors of maternal outcomes in the short term.…”

Section: Discussionmentioning

confidence: 99%

“…Stillbirths like a PE complication could rise at 30.2% 7,12. Future cardiovascular risk for the newborn caused by fetal programming has been also reported 3,11,13,14…”

Section: Introductionmentioning

confidence: 94%

“…Furthermore, long-term maternal morbidity has been recognized as being related to renal and cardiovascular risks 6–9. In newborns, its relation to intrauterine growth restriction and prematurity is well known,10 as well as to subsequent bronchopulmonary dysplasia, chronic lung disease, and neurodevelopmental delay 11. Stillbirths like a PE complication could rise at 30.2% 7,12.…”

Section: Introductionmentioning

confidence: 99%

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The umbilical cord, preeclampsia and the VEGF family

Contreras

Garrido

Hernández-Losa

et al. 2018

IJWH

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IntroductionThe VEGF family has been identified as abnormal in preeclampsia (PE). Hypertensive disorders of pregnancy (HDP) are major contributors to maternal and neonatal morbidity and mortality worldwide; likewise, umbilical cord anatomical abnormalities (UCAA) are linked to poor neonatal outcomes. Based on the relationship described between PE and UCAA and the role of the VEGF family in PE, this study explored VEGF expression in placental and UC tissued from patients with PE and with UCAA.MethodsWe performed an observational, analytical study on placentas, comparing protein and mRNA expression in four groups: patients with PE, patients with UC abnormalities, patients with both, and patients with none of them. Using immunohistochemistry, we studied VEGF A, VEGF R1 (FLT1), MMP1, and PLGF. With quantitative reverse transcription polymerase chain reaction we described mRNA expression of PLGF, VEGF and sFLT1, and sFLT1/PLGF ratio.ResultsForty newborns were included. Sixty-seven percent of mothers and 45% of newborns developed no complications. Immunohistochemistry was performed on UC and placental disc paraffin-embedded tissue; in the latter, the mRNA of the VEGF family was also measured. Statistically significant differences were observed among different expressions in both HDP and UCAA groups. Interestingly, the UCAA group exhibited lower levels of sFLT1 and VEGF-A in comparison with other groups, with significant P-value for sFLT1 (P=0000.1).ConclusionThe origin of UCAA abnormalities and their relation with HDP are still unknown. VEGF family alterations could be involved in both. This study provides the first approach related to molecules linked to UCAA.

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Section: Discussionmentioning

confidence: 99%

“…Stillbirths like a PE complication could rise at 30.2% 7,12. Future cardiovascular risk for the newborn caused by fetal programming has been also reported 3,11,13,14…”

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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The umbilical cord, preeclampsia and the VEGF family

Contreras

Garrido

Hernández-Losa

et al. 2018

IJWH

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“…The existence of functioning (healthy) vessels is a prerequisite for proper development and function of all other tissues and organs. Therefore, endothelial toxicity has a clear potential to affect the developmental path of many organs and tissues (18, 19). In this study, we present the first step in building a platform for screening of drugs and environmental toxicants for endothelial toxicity.…”

Section: Introductionmentioning

confidence: 99%

Initial Assessment of Variability of Responses to Toxicants in Donor-Specific Endothelial Colony Forming Cells

Filonov

Tice

Luo

et al. 2018

Front. Public Health

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There is increased interest in using high throughput in vitro assays to characterize human population variability in response to toxicants and drugs. Utilizing primary human endothelial colony-forming cells (ECFCs) isolated from blood would be highly useful for this purpose because these cells are involved in neonatal and adult vasculogenesis. We characterized the cytotoxicity of four known toxic chemicals (NaAsO2, CdCl2, tributyltin [TBT], and menadione) and their four relatively nontoxic counterparts (Na2HAsO4, ZnCl2, SnCl2, and phytonadione, respectively) in eight ECFC clones representing four neonatal donors (2 male and 2 female donors, 2 clones per donor). ECFCs were exposed to 9 concentrations of each chemical in duplicate; cell viability was evaluated 48 h later using the fluorescent vital dye fluorescent dye 5-Carboxyfluorescein Diacetate (CFDA), yielding concentration-effect curves from each experiment. Technical (day-to-day) variability of the assay, assessed from three independent experiments, was low: p-values for the differences of results were 0.74 and 0.64 for the comparison of day 2 vs. day 1 and day 3 vs. day 1, respectively. The statistical analysis used to compare the entire concentration-effect curves has revealed significant differences in levels of cytotoxicity induced by the toxic and relatively nontoxic chemical counterparts, demonstrating that donor-specific ECFCs can clearly differentiate between these two groups of chemicals. Partitioning of the total variance in the nested design assessed the contributions of between-clone and between-donor variability for different levels of cytotoxicity. Individual ECFC clones demonstrated highly reproducible responses to the chemicals. The most toxic chemical was TBT, followed by NaAsO2, CdCl2, and Menadione. Nontoxic counterparts exhibited low cytotoxicity at the higher end of concentration ranges tested. Low variability was observed between ECFC clones obtained from the same donor or different donors for CdCl2, NaAsO2, and TBT, but for menadione, the between-donor variability was much greater than the between-clone variability. The low between-clone variability indicates that an ECFC clone may represent an individual donor in cell-based assays, although this finding must be confirmed using a larger number of donors. Such confirmation would demonstrate that an in vitro ECFC-based testing platform can be used to characterize the inter-individual variability of neonatal ECFCs exposed to drugs and/or environmental toxicants.

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“…However, the results are inconclusive suggesting that further research is needed to unravel the mechanisms involved in alterations of EPCs in preterm birth and to identify potential new treatment modalities to restore their function. 1,2 We read with interest the recent report by Babaei et al, 3 which suggests that increased circulating levels of endothelial progenitor cells (cEPCs) may be associated with higher risk of ROP in preterm infants. 3 In this study, the authors evaluated the concentration of cEPCs and thoroughly analyzed the biological features of these cells, including secretion of angiogenic factors, proliferation, migration, and tubulogenesis activities.…”

mentioning

confidence: 99%