# An artery-on-a-chip system containing blood outgrowth endothelium as a model of vaso-occlusion and drug testing in sickle cell disease

> **NIH NIH R21** · TEXAS ENGINEERING EXPERIMENT STATION · 2020 · $175,087

## Abstract

An artery-on-a-chip system containing blood outgrowth endothelium as a model of vaso-occlusion and
drug testing in sickle cell disease
Challenge: Sickle cell disease (SCD) is a vascular and hematological disorder in which there is a fundamental
gap in the understanding of: 1) how organ-level signaling occurs in arterial blood vessels and why it varies from
patient to patient, and 2) how cells inside the vascular organ contribute to vaso-occlusions. The persistence of
this problem is partly due to the fact that animal models do not represent SCD faithfully, and as a result cannot
predict the responses to drugs relevant to humans. Recent advances in organ-on-a-chip technology have
permitted co-culture of human cells in physiologically-relevant microfluidic environments and also allowed whole
blood perfusion, providing an alternative in vitro approach to mimic the human disease. These microsystems
however, still have not reached their full potential due to variability of generic cell lines used, and absence of
efficient and scalable primary human patient cells. To meet these complex challenges, the applicant’s goal here
is to develop a new class of microphysiological system that contain all autologous vascular and blood cells easily
drawn from blood samples of the same human subject. Proposal: The objective is to design and establish the
feasibility of an artery-on-a-chip system that contains culture of autologous human blood outgrowth endothelial
cells (BOECs), permits the perfusion of whole blood of the same patient and provides dynamic cellular and
molecular readouts that help dissect SCD pathophysiology and drugs. The research proposed is innovative,
because it contributes in shifting the focus of modeling vascular pathophysiology from animal models to using
organ-on-a-chip platform containing only autologous cells. Here, the central hypothesis is that in the presence
of BOECs of SCD patients, the same patient’s blood cells and platelets will adhere more rapidly to the
endothelium when compared to generic cell lines. Secondly, treatment of BOECs with hydroxyurea may inhibit
such platelet-endothelium interactions, depending upon the patient’s history of stroke. Guided by the applicant’s
recent publications and collaboration with an expert in biology and hematology, two specific aims will be pursued:
1) demonstrate an artery-on-a-chip with BOECs and 2) determine tissue-specific effects of hydroxyurea
treatment in SCD occlusion. Outcomes: Under Aim #1, this new platform will enable blood to be perfused
through the vascular channel of the same patient. This system will also allow precise measurements of cell
adhesion, cytokines and vaso-occlusion. Under Aim #2, the treatment of this autologous SCD artery-on-a-chip
with hydroxyurea will provide insight into its specific therapeutic effects on the patient endothelium and blood
cells. It will also inform dosing requirements in patients who had a prior stroke vs who did not. Significance: The
outcomes w...

## Key facts

- **NIH application ID:** 9966991
- **Project number:** 5R21EB025945-03
- **Recipient organization:** TEXAS ENGINEERING EXPERIMENT STATION
- **Principal Investigator:** Abhishek Jain
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $175,087
- **Award type:** 5
- **Project period:** 2018-09-18 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966991

## Citation

> US National Institutes of Health, RePORTER application 9966991, An artery-on-a-chip system containing blood outgrowth endothelium as a model of vaso-occlusion and drug testing in sickle cell disease (5R21EB025945-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9966991. Licensed CC0.

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