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

authored by: 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.
Organisation(s): Institute of Cell Biology and Biophysics
External Organisation(s): Karlsruhe Institute of Technology (KIT)
Leibniz Institute of Polymer Research Dresden (IPF)
Type: Article
Journal: Advanced healthcare materials
Volume: 13
No. of pages: 21
ISSN: 2192-2640
Publication date: 01.09.2024
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Biomaterials, Biomedical Engineering, Pharmaceutical Science
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1002/adhm.202304157 (Access: Open)

BibTeX

@article{da0bb1695bd44692a9b78eec35b1ab72,
title = "A Multifunctional Nanostructured Hydrogel as a Platform for Deciphering Niche Interactions of Hematopoietic Stem and Progenitor Cells",
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.",
keywords = "block copolymer micelle nanolithography, differentiation, hematopoietic stem cells, integrins, multifunctionality, nanostructures, two dimensional hydrogels",
author = "Anita Ludwig-Husemann and Peter Schertl and Ananya Shrivastava and Udo Geckle and Johanna Hafner and Frank Schaarschmidt and Norbert Willenbacher and Uwe Freudenberg and Carsten Werner and Cornelia Lee-Thedieck",
note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH.",
year = "2024",
month = sep,
day = "1",
doi = "10.1002/adhm.202304157",
language = "English",
volume = "13",
journal = "Advanced healthcare materials",
issn = "2192-2640",
publisher = "John Wiley and Sons Ltd",
number = "22",
}