A Multifunctional Nanostructured Hydrogel as a Platform for Deciphering Niche Interactions of Hematopoietic Stem and Progenitor Cells

verfasst von
Anita Ludwig-Husemann, Peter Schertl, Ananya Shrivastava, Udo Geckle, Johanna Hafner, Frank Schaarschmidt, Norbert Willenbacher, Uwe Freudenberg, Carsten Werner, Cornelia Lee-Thedieck
Abstract

For over half a century, hematopoietic stem cells (HSCs) have been used for transplantation therapy to treat severe hematologic diseases. Successful outcomes depend on collecting sufficient donor HSCs as well as ensuring efficient engraftment. These processes are influenced by dynamic interactions of HSCs with the bone marrow niche, which can be revealed by artificial niche models. Here, a multifunctional nanostructured hydrogel is presented as a 2D platform to investigate how the interdependencies of cytokine binding and nanopatterned adhesive ligands influence the behavior of human hematopoietic stem and progenitor cells (HSPCs). The results indicate that the degree of HSPC polarization and motility, observed when cultured on gels presenting the chemokine SDF-1α and a nanoscale-defined density of a cellular (IDSP) or extracellular matrix (LDV) α4β1 integrin binding motif, are differently influenced on hydrogels functionalized with the different ligand types. Further, SDF-1α promotes cell polarization but not motility. Strikingly, the degree of differentiation correlates negatively with the nanoparticle spacing, which determines ligand density, but only for the cellular-derived IDSP motif. This mechanism potentially offers a means of predictably regulating early HSC fate decisions. Consequently, the innovative multifunctional hydrogel holds promise for deciphering dynamic HSPC-niche interactions and refining transplantation therapy protocols.

Organisationseinheit(en)
Institut für Zellbiologie und Biophysik
Externe Organisation(en)
Karlsruher Institut für Technologie (KIT)
Leibniz-Institut für Polymerforschung Dresden e.V.
Typ
Artikel
Journal
Advanced healthcare materials
Band
13
Anzahl der Seiten
21
ISSN
2192-2640
Publikationsdatum
01.09.2024
Publikationsstatus
Veröffentlicht
Peer-reviewed
Ja
ASJC Scopus Sachgebiete
Biomaterialien, Biomedizintechnik, Pharmazeutische Wissenschaften
Ziele für nachhaltige Entwicklung
SDG 3 – Gute Gesundheit und Wohlergehen
Elektronische Version(en)
https://doi.org/10.1002/adhm.202304157 (Zugang: Offen)