Aspirin-Mediated Reset of Preeclamptic Placental Stem Cell Transcriptome – Implication for Stabilized Placental Function

Romagano, Matthew P.; Sherman, Lauren S.; Shadpoor, Bobak; El-Far, Markos H.; Souayah, S.; Pamarthi, Sri Harika; Kra, Joshua; Hood-Nehra, Anupama; Etchegaray, Jean‐Pierre; Williams, Shauna F.; Rameshwar, Pranela

doi:10.1007/s12015-022-10419-8

Cited by 5 publications

(16 citation statements)

References 73 publications

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“…Primary stem cells such as mesenchymal stem cells (MSCs) from different sources such as bone marrow, adipose and placenta do not require large number of cells in one vial [9][10][11]. However, unlike hematopoietic cells, MSCs are easily expanded, which could allow for early cryostorage of expanded MSCs.…”

Section: Discussionmentioning

confidence: 99%

Cryopreservation of Large Number of Human Hematopoietic Cells – A Model for Research Space with Limited Resources

Ayer,

Greco,

Guiro

et al. 2024

IJTS

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Unlike cell lines, cells from primary human tissues are valuable, requiring storage for long-term use. Large number of primary cells require the most efficient method of shipment, when relevant, and cryopreservation to preserve the viability and function. Shipping of cells could be determined by the specific experimental question. These issues are particularly important for primary cells such as hematopoietic stem cells, which cannot expand in vitro. There is minimum issues when cryopreserving relatively small number of cells from tissues such as umbilical cord blood and bone marrow aspirates. However, cryopreservation of >200 × 109 primary cells comes with challenges to identify the most efficient method for long-term storage. Here we report on processes to achieve efficient cell health and recovery of hematopoietic cells from mobilized peripheral blood cells (MPBs). We also determined overnight shipment of MPBs led to overall outcomes when shipped in the cold, as compared to room temperature. We found that cryopreservation of 50 × 106 cells in 2 mL led to maximum recovery of hematopoietic cell subsets. The implication for these conditions to achieve efficient long-term storage is discussed. These methods will benefit small research laboratories such as those at academic settings and start-up companies with limited resources.

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Section: Discussionmentioning

confidence: 99%

Cryopreservation of Large Number of Human Hematopoietic Cells – A Model for Research Space with Limited Resources

Ayer,

Greco,

Guiro

et al. 2024

IJTS

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“…The only treatment currently available is termination of the pregnancy. Low-dose aspirin in early pregnancy has been shown to prevent PE, but only if taken before 16 weeks’ gestation 5 6 7 . Thus, it is crucial to screen during the first trimester in order to effectively prevent PE 8 .…”

Section: Introductionmentioning

confidence: 99%

The NFκB Signaling Pathway Is Involved in the Pathophysiological Process of Preeclampsia

Li,

Zhu,

et al. 2024

Geburtshilfe Frauenheilkd

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The high prevalence of preeclampsia (PE) is a major cause of maternal and fetal mortality and affects the long-term prognosis of both mother and baby. Termination of pregnancy is currently the only effective treatment for PE, so there is an urgent need for research into its pathogenesis and the development of new therapeutic approaches. The NFκB family of transcription factors has an essential role in inflammation and innate immunity. In this review, we summarize the role of NFκB in normal and preeclampsia pregnancies, the role of NFκB in existing treatment strategies, and potential NFκB treatment strategies.

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“…Aspirin is a cyclooxygenase inhibitor with anti-inflammatory and antiplatelet properties, and used to prevent or delay the onset of PE [14]. Aspirin inhibits two cyclooxygenase isoenzymes (COX-1 and COX-2), which are necessary for prostaglandin biosynthesis [13].…”

Section: Introductionmentioning

confidence: 99%

“…This particular response to ASA would benefit the inflammation in PE subjects since TGF-β could increase regulatory T-cells to maintain fetal-maternal tolerance [24,25]. The fetal-maternal surface has layers of placenta stem cells (P-MSCs) that share properties with mesenchymal stem cells (MSC) [14,26]. The nomenclature used in this study to describe P-MSCs follows guidelines by the International Council for Commonality in Blood Banking Automation-International Society for Cell and Gene Therapy [27].…”

Section: Introductionmentioning

confidence: 99%

“…An inflammatory milieu could license MSCs to exert immune suppression with the relevant skewing of the immune response such as increased Tregs [34][35][36]. Despite several layers of P-MSCs at the surface of the placenta, it is unclear why the layers of P-MSCs cannot be licensed as immune suppressor to mitigate the enhanced inflammation in PE subjects [14].…”

Section: Introductionmentioning

confidence: 99%

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Restore Veto Property in Low Dose Aspirin/ASA Treated Preeclampsia Placenta Mesenchymal Stem Cells: Insights Into ASA-mediated Clinical Response*

Powell,

Sherman,

Shadpoor

et al. 2024

IJTS

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Preeclampsia (PE) is a pregnancy complication characterized by elevated blood pressure, proteinuria, and other laboratory abnormalities. PE affects 2–8% of pregnancies globally and can lead to preterm birth and other complications for the mother and fetus. Successful pregnancy depends on the ability of the mother’s immune system to tolerate the allogeneic fetus. However, in PE, this immune tolerance is exacerbated by inflammation. Transforming growth factor β (TGF-β) is important to retain an immune balance in healthy pregnancy. In PE, TGF-β level is reduced, with an imbalance of the T-cell subset pool to favor inflammation. Omics studies by our group reported an increase in TGF-β signaling when PE-derived placenta mesenchymal stem cells (P-MSCs) were treated with low dose aspirin (ASA). This correlated with increased cycling quiescence and epigenetic changes, resembling healthy P-MSCs. This study tested the hypothesis that ASA could restore the veto property of P-MSCs to mitigate inflammation. ASA (10 mM) treated P-MSCs from PE and healthy placentas increased TGFβ1 and its receptor. The ASA treated MSCs, when added as third-party cells to a one-way mixed lymphocyte reaction, suppressed T-cell proliferation. Prediction studies with omics data indicated that ASA-mediated TGFβ signaling could explain ASA-induced blunting of cell apoptosis. Together, the findings support ASA-mediated expression of TGFβ1 and its receptor on P-MSCs from PE to restore the ability to be licensed as immune suppressor to mitigate PE inflammation. The findings provide new insight into the benefit of ASA treatment for PE.

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Aspirin-Mediated Reset of Preeclamptic Placental Stem Cell Transcriptome – Implication for Stabilized Placental Function

Cited by 5 publications

References 73 publications

Cryopreservation of Large Number of Human Hematopoietic Cells – A Model for Research Space with Limited Resources

Cryopreservation of Large Number of Human Hematopoietic Cells – A Model for Research Space with Limited Resources

The NFκB Signaling Pathway Is Involved in the Pathophysiological Process of Preeclampsia

Restore Veto Property in Low Dose Aspirin/ASA Treated Preeclampsia Placenta Mesenchymal Stem Cells: Insights Into ASA-mediated Clinical Response*

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