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Peer-reviewedCC BY-NCLab on a chip

A perfusable first-generation endometrial microvascular model to study human spiral artery remodeling in pregnancy.

  1. 1Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, Massachusetts, USA. [email protected].
  2. 2Seoul National University, Gwanak-gu, Republic of Korea.

Abstract

Invasive placental cells, extravillous trophoblasts (EVT), remodel maternal vasculature to meet metabolic needs of the growing fetus. Dysregulation of spiral artery remodeling (SAR) is a characteristic of preeclampsia (PE), a severe pregnancy-related condition. We developed a modular new approach methodology (NAM) of human endometrial-specific vascular networks in a polystyrene (PS) microfluidic chip to recapitulate the intricate endometrial vascular microenvironment to investigate SAR. We leveraged the self-assembly of human endometrial microvascular endothelial cells (HEMEC) and normal human lung fibroblasts (NHLF) to successfully develop patent endometrial vascular networks after 3 days of culture. Exogenous proangiogenic factors significantly improved vascular density while maintaining intrinsic endometrial vascular properties. Treatments of menstrual cycle phase-specific hormones differentially affected endometrial vascular density, diameter, permeability, and endogenous secretions of proangiogenic proteins. We evaluated integration potential of EVT cell lines HTR8/SVneo and JEG-3. We measured decreased barrier function and observed increased presence of apoptotic HEMECs after 3 days of tri-culture with JEG-3 cells, whereas HTR8/SVneo-induced apoptosis remained statistically unchanged across days 1 and 3 of integration. Moreover, we confirm HTR8/SVneo and JEG-3 cells differentially interact with HEMEC vasculature and the surrounding perivascular niche. These studies demonstrate the utility of our model to study endometrial vascularization and EVT remodeling.

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BibTeX
@article{naranjo2026perfusable,
  title = {{A perfusable first-generation endometrial microvascular model to study human spiral artery remodeling in pregnancy.}},
  author = {Sebastian Naranjo and Madison E Fletcher and Noo Li Jeon and Joyce Y Wong and Catherine Klapperich},
  journal = {Lab on a chip},
  year = {2026},
  month = oct,
  doi = {10.1039/d6lc00513f},
  url = {https://europepmc.org/article/MED/42852710},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - A perfusable first-generation endometrial microvascular model to study human spiral artery remodeling in pregnancy.
AU  - Sebastian Naranjo
AU  - Madison E Fletcher
AU  - Noo Li Jeon
AU  - Joyce Y Wong
AU  - Catherine Klapperich
PY  - 2026
DA  - 2026/10/09
JO  - Lab on a chip
DO  - 10.1039/d6lc00513f
UR  - https://europepmc.org/article/MED/42852710
AB  - Invasive placental cells, extravillous trophoblasts (EVT), remodel maternal vasculature to meet metabolic needs of the growing fetus. Dysregulation of spiral artery remodeling (SAR) is a characteristic of preeclampsia (PE), a severe pregnancy-related condition. We developed a modular new approach methodology (NAM) of human endometrial-specific vascular networks in a polystyrene (PS) microfluidic chip to recapitulate the intricate endometrial vascular microenvironment to investigate SAR. We leveraged the self-assembly of human endometrial microvascular endothelial cells (HEMEC) and normal human lung fibroblasts (NHLF) to successfully develop patent endometrial vascular networks after 3 days of culture. Exogenous proangiogenic factors significantly improved vascular density while maintaining intrinsic endometrial vascular properties. Treatments of menstrual cycle phase-specific hormones differentially affected endometrial vascular density, diameter, permeability, and endogenous secretions of proangiogenic proteins. We evaluated integration potential of EVT cell lines HTR8/SVneo and JEG-3. We measured decreased barrier function and observed increased presence of apoptotic HEMECs after 3 days of tri-culture with JEG-3 cells, whereas HTR8/SVneo-induced apoptosis remained statistically unchanged across days 1 and 3 of integration. Moreover, we confirm HTR8/SVneo and JEG-3 cells differentially interact with HEMEC vasculature and the surrounding perivascular niche. These studies demonstrate the utility of our model to study endometrial vascularization and EVT remodeling.
SN  - 1473-0197
SN  - 1473-0189
ER  -