Dissemin is shutting down on January 1st, 2025

Published in

Wiley Open Access, Bioengineering and Translational Medicine, 2(8), 2022

DOI: 10.1002/btm2.10454

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Integrated role of human thymic stromal cells in hematopoietic stem cell extravasation

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

AbstractThe human thymus is the site of T‐cell maturation and induction of central tolerance. Hematopoietic stem cell (HSC)‐derived progenitors are recruited to the thymus from the fetal liver during early prenatal development and from bone marrow at later stages and postnatal life. The mechanism by which HSCs are recruited to the thymus is poorly understood in humans, though mouse models have indicated the critical role of thymic stromal cells (TSC). Here, we developed a 3D microfluidic assay based on human cells to model HSC extravasation across the endothelium into the extracellular matrix. We found that the presence of human TSC consisting of cultured thymic epithelial cells (TEC) and interstitial cells (TIC) increases the HSC extravasation rates by 3‐fold. Strikingly, incorporating TEC or TIC alone is insufficient to perturb HSC extravasation rates. Furthermore, we identified complex gene expressions from interactions between endothelial cells, TEC and TIC modulates the HSCs extravasation. Our results suggest that comprehensive signaling from the complex thymic microenvironment is crucial for thymus seeding and that our system will allow manipulation of these signals with the potential to increase thymocyte migration in a therapeutic setting.