Watson, Sara A;
Javanmardi, Yousef;
Zanieri, Luca;
Shahreza, Somayeh;
Ragazzini, Roberta;
Bonfanti, Paola;
Moeendarbary, Emad;
(2022)
Integrated role of human thymic stromal cells in hematopoietic stem cell extravasation.
Bioengineering & Translational Medicine
, Article e10454. 10.1002/btm2.10454.
(In press).
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Abstract
The 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.
| Type: | Article |
|---|---|
| Title: | Integrated role of human thymic stromal cells in hematopoietic stem cell extravasation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/btm2.10454 |
| Publisher version: | https://doi.org/10.1002/btm2.10454 |
| Language: | English |
| Additional information: | Copyright © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | drug discovery and development, lymphoid progenitors, microfluidic devices, organ-mimetic systems, regenerative medicine, thymus on a chip, tissue engineering |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10160848 |
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