Integrated role of human thymic stromal cells in hematopoietic stem cell extravasation
More about Open Access at the CrickAuthors list
Sara Watson Yousef Javanmardi Luca Zanieri Somayeh Shahreza Roberta Ragazzini Paola Bonfanti Emad MoeendarbaryAbstract
The human thymus is the site of T-cell maturation andninduction 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.
Journal details
Volume 8
Issue number 2
Pages e10454
Available online
Publication date
Full text links
Publisher website (DOI) 10.1002/btm2.10454
Europe PubMed Central 36925684
Pubmed 36925684
Keywords
Related topics
Type of publication