The effects of preeclampsia on signaling to hematopoietic progenitor cells

Santillan, Donna A.; Hamilton, Wendy S.; Christensen, Ashley; Talcott, Katelyn M.; Gravatt, Lindsay; Santillan, Mark K.; Hunter, Stephen K.

doi:10.17077/2154-4751.1207

Cited by 6 publications

(7 citation statements)

References 18 publications

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“…Our results were in agreement with previous reports [27,48] demonstrating no significant differences in the frequency of UCB HSPCs or the expression of the SAMs on these cells, despite originating from PE or normotensive pregnancies. In addition, the absence of significant differences in the number of BFU-Es produced during in vitro differentiation of the UCB CD34 + cells from PE and normotensive groups in our samples was in accordance with previous reports [26,27]. Interestingly, both function and expression of SAMs on HSPCs are precisely regulated during embryonic development [49,50,51] as well as lineage differentiation [47,52,53].…”

Section: Discussionsupporting

confidence: 92%

“…Higher erythroblast count in the UCB is a common observation in PE pregnancies [18,19,20,21] that has been linked to elevated erythropoiesis induced by hypoxia and enhanced fetal erythropoietin (EPO) levels [22,23,24,25]. However, previous studies investigating in vitro colony formation of UCB HSPCs have not demonstrated any significant differences in the erythroid differentiation capacity of the cells obtained from PE vs. normotensive pregnancies [26,27]. This suggests that a mechanism other than hypoxia-induced EPO-dependent enhanced fetal erythropoiesis may affect erythroid maturation, underlying the higher erythroblast count documented in the UCB of PE pregnancies.…”

Section: Introductionmentioning

confidence: 99%

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Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells

Masoumi

Maes

Herten

et al. 2019

IJMS

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Preeclampsia (PE) has been associated with placental dysfunction, resulting in fetal hypoxia, accelerated erythropoiesis, and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional, and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression of surface adhesion molecules and the erythroid differentiation capacity of UCB hematopoietic stem/progenitor cells (HSPCs), UCB erythroid profiles along with the transcriptome and proteome of these cells between male and female fetuses from PE and normotensive pregnancies. While no significant differences were observed in UCB HSPC migration/homing and in vitro erythroid colony differentiation, the UCB HSPC transcriptome and the proteomic profile of the in vitro differentiated erythroid cells differed between PE vs. normotensive samples. Accordingly, despite the absence of significant differences in the UCB erythroid populations in male or female fetuses from PE or normotensive pregnancies, transcriptional changes were observed during erythropoiesis, particularly affecting male fetuses. Pathway analysis suggested deregulation in the mammalian target of rapamycin complex 1/AMP-activated protein kinase (mTORC1/AMPK) signaling pathways controlling cell cycle, differentiation, and protein synthesis. These results associate PE with transcriptional and proteomic changes in fetal HSPCs and erythroid cells that may underlie the higher erythroblast count in the UCB in PE.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells

Masoumi

Maes

Herten

et al. 2019

IJMS

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“…The long term alteration pattern of the haematopoietic growth factors and cytokines in the foetus might have influence on haematopoietic activity in the progenitor cell population (Surbek et al 2001). The abnormalities in the placenta due to PE also may affect the ability of haematopoietic stem cells to grow and differentiate (Santillan et al 2013). In the GDM group, the effects of GDM on UCB HSC have not been well studied.…”

Section: Resultsmentioning

confidence: 99%

Total Nucleated Cell Count and CD34+ Cell is Reduced in Preeclampsia and Gestational Diabetes Mellitus Pregnancies: Viable Affix Criteria for Cord Blood Banking

Idris

Nordin²,

Mahdy³

et al. 2018

JSM

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The aim of this study to determine the numbers of CD34+ cells and total nucleated cell (TNC) in umbilical cord blood (UCB) collected from pregnant mothers with gestational diabetes mellitus (GDM) and preeclampsia (PE), following statistical analysis of both maternal and perinatal factors which affect UCB parameters. Most of studies explored the influence of obstetric factors on the number of UCB cell collection and only a few looked at the effects on UCB haematopoietic stem cell (UCB-HSC) of common disorders complicating pregnancy. A total of 112 UCB samples (32 PE, 42 GDM and 38 nondiseased) were collected. CD34 + cell and NC count were enumerated using FACS Calibur. The TNC and CD34 + cells were significantly reduced in both PE and GDM groups as compared to the control group. The PE group shows significantly lower birth weight and higher BP which led to a lower UCB volume and CD34 + count. Gestational age shows significant correlation with nucleated cell count (NCC) and TNC. GDM group shows significantly lower systolic BP, NCC and TNC count, including low placental weight and birth weight. Conclusively, some obstetrics factors have significant influences to the numbers and quality of UCB-HSC in both PE and GDM groups, which could guide in the selection criteria for CB banking.

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“…In a study conducted by Gauster et al (2012), it was concluded that high levels of insulin in the UCB plasma could interfere with foetal growth and subsequently alter the process of angiogenesis and vascularization that could affect the quality of UCB-HSC (Gauster et al 2012). These two cytokines, EPO and insulin, may provide a good microenvironment for cell growth and haematopoiesis (Santillan et al 2013), thus producing good quality HSC. High EPO levels always correlated with diabetic pregnancies and hypoxia, whilst higher insulin might impair the match between supply and demand from the placenta.…”

Section: Introductionmentioning

confidence: 99%

Gestational diabetes mellitus in pregnancy increased erythropoietin level affecting differentiation potency of haematopoietic stem cell of umbilical cord blood

Nordin

Idris

Mahdy

et al. 2020

Preprint

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Abstract Background The in utero environment has many factors that can support cell differentiation. Cytokines, chemokines and growth factors play big roles in haematopoietic mechanisms. Some diseases like gestational diabetes mellitus (GDM) might affect the environment and haematopoietic stem cell (HSC) quality. The aim of this study is to investigate the adverse effects of GDM on umbilical cord blood (UCB) HSC in terms of differentiation potency including the UCB parameters used for banking and transplantation purposes. Methods UCB-HSC was isolated and further enriched using immuno-magnetic separation beads (MACS). The UCB-HSC were cultured in methylcellulose media to investigate the differentiation potency. The level of erythropoietin (EPO) and insulin in the UCB plasma was measured using enzyme linked immunoassay (ELISA) technique. Results The UCB parameters; volume, total nucleated count (TNC) and total CD34+ cells were significantly reduced in the GDM group compared to the control group. The number of HSC progenitors’ colonies were significantly reduced in the GDM group except for progenitor BFU-E, which was significantly increased (GDM=94.19 ± 6.21, Control=73.61 ± 2.73, p=0.010 ). This data was associated with higher EPO level in GDM group. However, the insulin level in the GDM group was comparable to the Control group. Conclusion Our results suggest that the changes in the in utero environment due to abnormalities during pregnancy such as GDM affect the differentiation potency of UCB-HSC. These findings can be considered as an additional parameter for the inclusion and exclusion criteria for UCB banking, particularly for mothers with GDM.

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The effects of preeclampsia on signaling to hematopoietic progenitor cells

Cited by 6 publications

References 18 publications

Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells

Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells

Total Nucleated Cell Count and CD34+ Cell is Reduced in Preeclampsia and Gestational Diabetes Mellitus Pregnancies: Viable Affix Criteria for Cord Blood Banking

Gestational diabetes mellitus in pregnancy increased erythropoietin level affecting differentiation potency of haematopoietic stem cell of umbilical cord blood

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