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Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell
Naomi Todd1, Ross McNally1, Abdelrahim Alqudah1,2
1The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, UK.
Insights
Preeclampsia risk can be predicted using the CD44/FK506-binding protein like (FKBPL) ratio in plasma. This ratio, combined with blood pressure, offers early diagnostic and therapeutic targets for this pregnancy complication.
Area of Science:
- Obstetrics and Gynecology
- Cardiovascular Medicine
- Biochemistry
Background:
- Preeclampsia is a significant pregnancy complication with limited diagnostic and treatment options.
- Effective strategies for early detection and management of preeclampsia are urgently needed.
Purpose of the Study:
- To evaluate the potential of angiogenesis proteins FK506-binding protein like (FKBPL) and CD44 as diagnostic and therapeutic targets for preeclampsia.
- To investigate the role of the FKBPL-CD44 pathway in preeclampsia pathogenesis.
Main Methods:
- Quantified FKBPL and CD44 plasma concentrations and placental expression in preeclamptic and healthy pregnant women.
- Assessed trophoblast and endothelial cell function following mesenchymal stem cell (MSC) treatment and FKBPL signaling.
- Utilized human samples from prediagnosis (15-20 weeks gestation) and postdiagnosis stages.
Main Results:
- A reduced CD44/FKBPL ratio was observed in placenta and plasma post-preeclampsia diagnosis.
- A high plasma CD44/FKBPL ratio at 20 weeks gestation independently predicted a 2.3-fold increased preeclampsia risk.
- Combined with high mean arterial pressure, the risk prediction increased to 3.9-fold. MSC therapy and hypoxia modulated FKBPL-CD44 signaling, enhancing angiogenesis.
Conclusions:
- The FKBPL-CD44 pathway plays a crucial role in preeclampsia development.
- FKBPL and CD44 show promise as early diagnostic markers for preeclampsia.
- The FKBPL-CD44 pathway presents a potential therapeutic target for preeclampsia management.
Context:
Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.
Objective:
To investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44.
Design And Intervention:
FKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling.
Settings And Participants:
Human samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid.
Main Outcome Measures:
Preeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed.
Results:
The CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis.
Conclusions:
The FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.
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